Stem cell biobanks.

PubMed

Bardelli, Silvana

2010-04-01

Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

Concepts, Utility and Limitations of Cord Blood Banking: What Clinicians Need to Know.

PubMed

Narayanan, Dhanya Lakshmi; Phadke, Shubha R

2018-03-20

Stem cell transplantation and cord blood banking have received much popularity among general public and medical professionals in the recent past. But information about the scientific aspects, its utility and limitations is incomplete amongst laypersons as well as many medical practitioners. Stem cells differ from all other types of cells in the human body because of their ability to multiply in order to self perpetuate and differentiate into specialized cells. Stems cells could be totipotent, multipotent, pluripotent, oligopotent or unipotent depending on the type of cells that can arise or differentiate from them. Umbilical cord blood serves as a potent source of hematopoeitic stem cells and is being used to treat various disorders like blood cancers, hemoglobinopathies and immunodeficiency disorders for which hematological stem cell transplantation is the standard of care. Cord blood can be collected at ease, without any major complications and has a lower incidence of graft vs. host reaction compared to bone marrow cells or peripheral blood cells. Both public and private banks have been established for collection and storage of umbilical cord blood. However, false claims and misleading commercial advertisements about the use of umbilical cord blood stem cells for the treatment of a variety of conditions ranging from neuromuscular disorders to cosmetic benefits are widespread and create unrealistic expectations in laypersons and clinicians. Many clinicians and laypersons are unaware of the limitations of cord blood banking, as in treating a genetic disorder by autologous cord blood transplant. Knowledge and awareness about the scientific indications of cord blood stem cell transplantation and realistic expectations about the utility of cord blood among medical practitioners are essential for providing accurate information to laypersons before they decide to preserve umbilical cord blood in private banks and thus prevent malpractice.

[Private umbilical cord blood banking does not reduce the number of samples for scientific stem cell research].

PubMed

Jacobs, V R; Niemeyer, M; Gottschalk, N; Schneider, K T; Kiechle, M

2005-12-01

Private umbilical cord blood (UCB) banking after delivery has increased over the last decade. For adult/somatic stem cell research UCB is an essential source of stem cells and researchers question if the number of UCB samples for research might be reduced by private banking. A survey among seven private blood banks in Germany and analysis and comparison of the number of UCB samples donated for research within the STEMMAT project with private blood banking were performed from 03/2003 to 06/2005 at the Frauenklinik (OB/GYN), Technical University Munich, Germany. Within 27.5 months 1,551 UCB samples were collected for research purposes; the effective recruitment rate was higher than expectations at an effective 66.2 %. Private UCB banking [n = 24] was distributed among three cord blood banks [n = 16, 6 and 4]. The rate of private blood banking was 0.99 % for all deliveries, thus reducing the effective rate for research purpose by only 1.5 %. Under the assumption of active and successful recruitment of scientific UCB samples, private blood banking does not significantly reduce this rate and therefore is a negligible rival in the competition for sufficient numbers of UCB samples for research.

Biobanking human embryonic stem cell lines: policy, ethics and efficiency.

PubMed

Holm, Søren

2015-12-01

Stem cell banks curating and distributing human embryonic stem cells have been established in a number of countries and by a number of private institutions. This paper identifies and critically discusses a number of arguments that are used to justify the importance of such banks in policy discussions relating to their establishment or maintenance. It is argued (1) that 'ethical arguments' are often more important in the establishment phase and 'efficiency arguments' more important in the maintenance phase, and (2) that arguments relating to the interests of embryo and gamete donors are curiously absent from the particular stem cell banking policy discourse. This to some extent artificially isolates this discourse from the broader discussions about the flows of reproductive materials and tissues in modern society, and such isolation may lead to the interests of important actors being ignored in the policy making process.

Cord Blood Banking Standards: Autologous Versus Altruistic

PubMed Central

Armitage, Sue

2016-01-01

Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as “biological insurance” should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485

Human Finger-Prick Induced Pluripotent Stem Cells Facilitate the Development of Stem Cell Banking

PubMed Central

Tan, Hong-Kee; Toh, Cheng-Xu Delon; Ma, Dongrui; Yang, Binxia; Liu, Tong Ming; Lu, Jun; Wong, Chee-Wai; Tan, Tze-Kai; Li, Hu; Syn, Christopher; Tan, Eng-Lee; Lim, Bing; Lim, Yoon-Pin; Cook, Stuart A.

2014-01-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a “do-it-yourself” basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide. PMID:24646489

Impact of Selection of Cord Blood Units from the United States and Swiss Registries on the Cost of Banking Operations

PubMed Central

Bart, Thomas; Boo, Michael; Balabanova, Snejana; Fischer, Yvonne; Nicoloso, Grazia; Foeken, Lydia; Oudshoorn, Machteld; Passweg, Jakob; Tichelli, Andre; Kindler, Vincent; Kurtzberg, Joanne; Price, Thomas; Regan, Donna; Shpall, Elizabeth J.; Schwabe, Rudolf

2013-01-01

Background Over the last 2 decades, cord blood (CB) has become an important source of blood stem cells. Clinical experience has shown that CB is a viable source for blood stem cells in the field of unrelated hematopoietic blood stem cell transplantation. Methods Studies of CB units (CBUs) stored and ordered from the US (National Marrow Donor Program (NMDP) and Swiss (Swiss Blood Stem Cells (SBSQ)) CB registries were conducted to assess whether these CBUs met the needs of transplantation patients, as evidenced by units being selected for transplantation. These data were compared to international banking and selection data (Bone Marrow Donors Worldwide (BMDW), World Marrow Donor Association (WMDA)). Further analysis was conducted on whether current CB banking practices were economically viable given the units being selected from the registries for transplant. It should be mentioned that our analysis focused on usage, deliberately omitting any information about clinical outcomes of CB transplantation. Results A disproportionate number of units with high total nucleated cell (TNC) counts are selected, compared to the distribution of units by TNC available. Therefore, the decision to use a low threshold for banking purposes cannot be supported by economic analysis and may limit the economic viability of future public CB banking. Conclusions We suggest significantly raising the TNC level used to determine a bankable unit. A level of 125 × 107 TNCs, maybe even 150 × 107 TNCs, might be a viable banking threshold. This would improve the return on inventory investments while meeting transplantation needs based on current selection criteria. PMID:23637645

Documenting the doable and doing the documented: bridging strategies at the UK Stem Cell Bank.

PubMed

Stephens, Neil; Atkinson, Paul; Glasner, Peter

2011-12-01

We explore the local negotiation of regulatory practice at the UK Stem Cell Bank, the first Bank of its type in the world. Basing our empirical work on a detailed analysis of one aspect of the Bank's regulatory commitment--the completion of the Cell Line Information form--we make visible the necessary judgements and labour involved in interpreting and operationalizing externally imposed regulation. The discussion opens by detailing the problems encountered when the Bank completes the form: reconciling a bureaucratic system of accountability with craft-like laboratory skills involving multiple kinds of tacit knowledge. We follow this by explicating the emergent 'bridging strategies' pursued by the Bank to address these issues, highlighting their reliance upon the formation of trust and social networks. The closing discussion emphasizes the contingent assembly of regulatory practices that emerge in the local setting.

Effect of Induced Pluripotent Stem Cell Technology in Blood Banking

PubMed Central

Focosi, Daniele

2016-01-01

Summary Population aging has imposed cost-effective alternatives to blood donations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cells must be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stem cell (iPSC) technology could pave the way to a new era in transfusion medicine, just as it is already doing in many other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. Significance The aging population in Western countries is causing a progressive reduction of blood donors and a constant increase of blood recipients. Because blood is the main therapeutic option to treat acute hemorrhage, cost-effective alternatives to blood donations are being actively investigated. The enormous replication capability of induced pluripotent stem cells and their promising results in many other fields of medicine could be an apt solution to produce the large numbers of viable cells required in transfusion and usher in a new era in transfusion medicine. The present report describes the potentiality, technological hurdles, and promises of induced pluripotent stem cells to generate red blood cells by redifferentiation. PMID:26819256

Current overview on dental stem cells applications in regenerative dentistry.

PubMed

Bansal, Ramta; Jain, Aditya

2015-01-01

Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental stem cells were shortlisted and the facts are compiled. The objective of this review article is to discuss the history of stem cells, different stem cells relevant for dentistry, their isolation approaches, collection, and preservation of dental stem cells along with the current status of dental and medical applications.

Umbilical cord blood banking in the worldwide hematopoietic stem cell transplantation system: perspectives for Ukraine.

PubMed

Kalynychenko, T O

2017-09-01

Significant progress in the promotion of procedural technologies associated with the transplantation of hematopoietic stem cells caused a rapid increase in activity. The exchange of hematopoietic stem cells for unrelated donor transplantations is now much easier due to the relevant international professional structures and organizations established to support cooperation and standard setting, as well as rules for the functioning of both national donor registries and cord blood banks. These processes are increasing every year and are contributing to the outpacing rates of development in this area. Products within their country should be regulated by the competent government authorities. This study analyzes the work of international and national levels of support for transplantation activity in the field of unrelated hematopoietic stem cell transplantation, the standardization order of technologies, as well as data that justify the need to create a network of donated umbilical cord blood banks in Ukraine as a factor in the development of allogeneic transplantation. This will promote the accessibility of international standards for the treatment of serious diseases for Ukrainian citizens.

Establishing a public umbilical cord blood stem cell bank for South Africa: an enquiry into public acceptability.

PubMed

Meissner-Roloff, Madelein; Pepper, Michael S

2013-12-01

South Africa (SA) faces a large unmet need for bone marrow (BM) transplantation, which could be alleviated in part by establishing a public umbilical cord blood stem cell bank (UCB SCB). Umbilical cord blood is an increasingly utilised source of hematopoietic stem cells for BM transplantation in addition to BM or mobilized peripheral blood stem cells. Establishing a public UCB SCB would therefore be a positive step towards improving the quality of health care in SA by providing for an important unmet need. This study takes the form of an enquiry into the acceptability of establishing a public bank through an interview with and questionnaire completed by mothers-to-be in the antenatal clinic of a large public hospital in SA. Initial results are positive, with 85 % of the participants in favour of establishing a public UCB SCB in SA. This initial probe will serve as a model for a more comprehensive national enquiry into public support and acceptability in different clinics, hospitals and provinces in SA.

Banking Umbilical Cord Blood (UCB) Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India).

PubMed

Pandey, Deeksha; Kaur, Simar; Kamath, Asha

2016-01-01

The concept of Umbilical Cord blood (UCB) stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India). Obtaining this information may help optimize recruitment efforts and improve patient education. Present explorative questionnaire based survey included 254 pregnant women in the final analysis. We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1%) was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB. Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking.

Banking Umbilical Cord Blood (UCB) Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India)

PubMed Central

Pandey, Deeksha

2016-01-01

Background The concept of Umbilical Cord blood (UCB) stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India). Obtaining this information may help optimize recruitment efforts and improve patient education. Material and Method Present explorative questionnaire based survey included 254 pregnant women in the final analysis. Results We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1%) was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB. Conclusion Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking. PMID:27228155

Cord-Blood Banking

MedlinePlus

... cord blood mainly because of the promise that stem cell research holds for the future. Most of us would have little use for stem cells now, but research into using them to treat diseases is ongoing — ...

Maternal understanding of commercial cord blood storage for their offspring - a survey among pregnant women in Hong Kong.

PubMed

Suen, Stephen Sik Hung; Lao, Terence T; Chan, Oi Ka; Kou, Thomas Kam On; Chan, Sammy Chung Sum; Kim, Jean Hee; Lau, Tze Kin; Leung, Tak Yeung

2011-09-01

To assess the knowledge on commercial cord blood banking (CCBB) among pregnant women. Cross-sectional survey. Setting. Antenatal clinics of two major public maternity units in Hong Kong. Pregnant women. Self-administered questionnaire. The survey explored knowledge about the use of self-stored umbilical cord blood (UCB) stem cells and attitude towards CCBB. Of the 2,000 women recruited, 1 866 (93.3%) completed the questionnaire. The majority (78.2%) had no idea that there was the chance of using self-stored stem cells. Moreover, most of the respondents were unclear about which diseases other than leukemia are amenable to treatment with UCB stem cells in general. Only 20.3% of women knew that stem cells are available from the Red Cross in case their children need hematopoietic cell transplantation. The results of this study revealed inadequate knowledge on UCB stem cell banking and its applications among most of our pregnant women. The government and clinicians should combine efforts to provide accurate information on utilization of UCB stem cells during antenatal care. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Applications of Stem Cells in Interdisciplinary Dentistry and Beyond: An Overview

PubMed Central

Rai, S; Kaur, M; Kaur, S

2013-01-01

In medicine stem cell–based treatments are being used in conditions like Parkinson's disease, neural degeneration following brain injury, cardiovascular diseases, diabetes, and autoimmune diseases. In dentistry, recent exciting discoveries have isolated dental stem cells from the pulp of the deciduous and permanent teeth, from the periodontal ligament, and an associated healthy tooth structure, to cure a number of diseases. The aim of the study was to review the applications of stem cells in various fields of dentistry, with emphasis on its banking, and to understand how dental stem cells can be used for regeneration of oral and non-oral tissues conversely. A Medline search was done including the international literature published between 1989 and 2011. It was restricted to English language articles and published work of past researchers including in vitro and in vivo studies. Google search on dental stem cell banking was also done. Our understanding of mesenchymal stem cells (MSC) in the tissue engineering of systemic, dental, oral, and craniofacial structures has advanced tremendously. Dental professionals have the opportunity to make their patients aware of these new sources of stem cells that can be stored for future use, as new therapies are developed for a range of diseases and injuries. Recent findings and scientific research articles support the use of MSC autologously within teeth and other accessible tissue harvested from oral cavity without immunorejection. A future development of the application of stem cells in interdisciplinary dentistry requires a comprehensive research program. PMID:23919198

What Happens During a Bone Marrow Transplant? | NIH MedlinePlus the Magazine

MedlinePlus

... is frozen and stored at a cord blood bank for future use. Outlook Stem cell transplants have serious risks. Some complications are life threatening. For some people, however, stem cell transplants are the best hope ...

76 FR 19101 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-06

... Groups: Cord Blood Bank Collections, Realizing the Potential of Cord Blood, Scientific Factors Necessary... Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the... 19102

Development of a novel method for amniotic fluid stem cell storage.

PubMed

Zavatti, Manuela; Beretti, Francesca; Casciaro, Francesca; Comitini, Giuseppina; Franchi, Fabrizia; Barbieri, Veronica; Bertoni, Laura; De Pol, Anto; La Sala, Giovanni B; Maraldi, Tullia

2017-08-01

Current procedures for collection of human amniotic fluid stem cells (hAFSCs) indicate that cells cultured in a flask for 2 weeks can then be used for research. However, hAFSCs can be retrieved directly from a small amount of amniotic fluid that can be obtained at the time of diagnostic amniocentesis. The aim of this study was to determine whether direct freezing of amniotic fluid cells is able to maintain or improve the potential of a sub-population of stem cells. We compared the potential of the hAFSCs regarding timing of freezing, cells obtained directly from amniotic fluid aspiration (D samples) and cells cultured in a flask before freezing (C samples). Colony-forming-unit ability, proliferation, morphology, stemness-related marker expression, senescence, apoptosis and differentiation potential of C and D samples were compared. hAFSCs isolated from D samples expressed mesenchymal stem cells markers until later passages, had a good proliferation rate and exhibited differentiation capacity similar to hAFSCs of C samples. Interestingly, direct freezing induced a higher concentration of cells positive for pluripotency stem cell markers, without teratoma formation in vivo. This study suggests that minimal processing may be adequate for the banking of amniotic fluid cells, avoiding in vitro passages before the storage and exposure to high oxygen concentration, which affect stem cell properties. This technique might be a cost-effective and reasonable approach to the process of Good Manufacturing Process accreditation for stem-cell banks. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Unrelated haematopoietic stem cell transplantation in Taiwan and beyond.

PubMed

Yang, K L; Chang, C Y; Lin, S; Shyr, M H; Lin, P Y

2009-06-01

Since its inception in October 1993, the world-renowned Buddhist Tzu Chi Marrow Donor Registry has facilitated more than 1800 cases of stem cell donations for patients in 27 countries to date. Under the auspices of the Buddhist Tzu Chi Stem Cells Center (BTCSCC), the Registry (> 310,000 donors) offers, on average, one case of stem cell donation every day to national or international transplantation community. The accomplishment of the Registry stems from the philosophy and spirit of giving without reward that was inspired by its founder Dharma Master Cheng Yen, the Samaritan devotions of selfless voluntary stem cell donors and the efforts from a dedicated network of volunteer workers. Demographically speaking, slightly less than one third of the donations are provided to domestic patients and the rest to mainland China and countries in Asia, North America, Europe, Middle East, Oceania, and South Africa. While most of the patients belong to the Oriental ethnic group, a few of the patients are non-Oriental. In addition to the Registry, a non-profit umbilical cord blood (UCB) bank is operating since 2002 to provide a complimentary role for patients unable to identify appropriate bone marrow stem cell donors in the Registry in time. To date, with an inventory of over 12,000 units of UCB cryopreserved in the Tzu Chi Cord Blood Bank, 47 units have been employed in 37 cases of transplantation for both paediatric and adult patients domestically and internationally. The fact that Buddhist Tzu Chi Marrow Donor Registry and Cord Blood Bank are established and operating without governmental financial support is unique and special. To facilitate haematopoietic stem cells to its domestic patients experiencing financial burdens, the BTCSCC offers financial aids to the underprivileged for their medical relief. This humanitarian approach and compassion is definitely a role model for many countries in the world.

Cord blood stem cells for hematopoietic stem cell transplantation in the UK: how big should the bank be?

PubMed

Querol, Sergio; Mufti, Ghulam J; Marsh, Steven G E; Pagliuca, Antonio; Little, Ann-Margaret; Shaw, Bronwen E; Jeffery, Robert; Garcia, Joan; Goldman, John M; Madrigal, J Alejandro

2009-04-01

A stored cord blood donation may be a valuable source of hemopoietic stem cells for allogeneic transplantation when a matched sibling donor is not available. We carried out a study to define the optimal size of a national cord blood bank for the UK. We calculated the actual numbers of possible donors and the chance of finding at least one donor for 2,000 unselected and for 722 non-North Western European patients for whom searches had been initiated as a function of three levels of HLA matching (4, 5 and 6 out of 6 alleles by HLA-A, -B low and -DRB1 high resolution HLA typing) according to various donor bank sizes. With a bank size of 50,000, 80% of patients will have at least one donor unit available at the 5 out of 6 HLA allele match level (median 9 donors per patient), and 98% will have at least one donor at the 4 out of 6 allele match level (median 261). Doubling the size of the bank yields at least one donor for only an additional 6% of patients at the 5 of 6 allele match level. Moreover, for non-North Western European patients a 50,000 unit bank provides a donor for 50% at the 5 allele match level, and for 96% at the 4 allele match level. A bank containing 50,000 units is optimal for the UK and larger banks would only marginally increase the chance of finding suitable units.

Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience.

PubMed

De Sousa, Paul A; Steeg, Rachel; Wachter, Elisabeth; Bruce, Kevin; King, Jason; Hoeve, Marieke; Khadun, Shalinee; McConnachie, George; Holder, Julie; Kurtz, Andreas; Seltmann, Stefanie; Dewender, Johannes; Reimann, Sascha; Stacey, Glyn; O'Shea, Orla; Chapman, Charlotte; Healy, Lyn; Zimmermann, Heiko; Bolton, Bryan; Rawat, Trisha; Atkin, Isobel; Veiga, Anna; Kuebler, Bernd; Serano, Blanca Miranda; Saric, Tomo; Hescheler, Jürgen; Brüstle, Oliver; Peitz, Michael; Thiele, Cornelia; Geijsen, Niels; Holst, Bjørn; Clausen, Christian; Lako, Majlinda; Armstrong, Lyle; Gupta, Shailesh K; Kvist, Alexander J; Hicks, Ryan; Jonebring, Anna; Brolén, Gabriella; Ebneth, Andreas; Cabrera-Socorro, Alfredo; Foerch, Patrik; Geraerts, Martine; Stummann, Tina C; Harmon, Shawn; George, Carol; Streeter, Ian; Clarke, Laura; Parkinson, Helen; Harrison, Peter W; Faulconbridge, Adam; Cherubin, Luca; Burdett, Tony; Trigueros, Cesar; Patel, Minal J; Lucas, Christa; Hardy, Barry; Predan, Rok; Dokler, Joh; Brajnik, Maja; Keminer, Oliver; Pless, Ole; Gribbon, Philip; Claussen, Carsten; Ringwald, Annette; Kreisel, Beate; Courtney, Aidan; Allsopp, Timothy E

2017-04-01

A fast track "Hot Start" process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution. Here we report on the successful outcome of this experience and work flow for banking and facilitating access to an otherwise disparate European resource, with lessons to benefit the international research community. ETOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Safe and efficient method for cryopreservation of human induced pluripotent stem cell-derived neural stem and progenitor cells by a programmed freezer with a magnetic field.

PubMed

Nishiyama, Yuichiro; Iwanami, Akio; Kohyama, Jun; Itakura, Go; Kawabata, Soya; Sugai, Keiko; Nishimura, Soraya; Kashiwagi, Rei; Yasutake, Kaori; Isoda, Miho; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki

2016-06-01

Stem cells represent a potential cellular resource in the development of regenerative medicine approaches to the treatment of pathologies in which specific cells are degenerated or damaged by genetic abnormality, disease, or injury. Securing sufficient supplies of cells suited to the demands of cell transplantation, however, remains challenging, and the establishment of safe and efficient cell banking procedures is an important goal. Cryopreservation allows the storage of stem cells for prolonged time periods while maintaining them in adequate condition for use in clinical settings. Conventional cryopreservation systems include slow-freezing and vitrification both have advantages and disadvantages in terms of cell viability and/or scalability. In the present study, we developed an advanced slow-freezing technique using a programmed freezer with a magnetic field called Cells Alive System (CAS) and examined its effectiveness on human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs). This system significantly increased cell viability after thawing and had less impact on cellular proliferation and differentiation. We further found that frozen-thawed hiPSC-NS/PCs were comparable with non-frozen ones at the transcriptome level. Given these findings, we suggest that the CAS is useful for hiPSC-NS/PCs banking for clinical uses involving neural disorders and may open new avenues for future regenerative medicine. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[The cord blood bank at the Instituto Mexicano del Seguro Social].

PubMed

Peñaflor-Juárez, Karina; Guillén-Chan, Sonia Marilyn; Romero-Juárez, Yanín; Luna-Bautista, Fernando; Franco-Gutiérrez, Elizabeth; Arellano-Ocampo, Jesús Salvador; Ibáñez-Sánchez, Rocío; de Lourdes Domínguez-Contreras, María; Guerra-Márquez, Angel

2015-01-01

Hematopoietic stem cells have been used for over 50 years in the treatment of diverse diseases. Umbilical cord blood (UCB) has proved to be a viable source of hematopoietic stem cells for transplantation purposes. The aim was to report the contribution of the umbilical cord blood bank over the past 9 years, in the treatment of various diseases. Since 2005 the number of units of blood from the umbilical cord and their use for transplantation in diverse disease were analyzed. A selection of volunteer pregnant women in labor was performed. Umbilical cord blood was obtained from them, which underwent processing, cryopreservation and validation, as well as compatibility test before using for transplantation. Ten thousand and ninety nine candidates to donation were assessed, from whom 2481 unit of UCB were collected. Of these, 893 unit were processed and cryopreserved for transplantation. In 65% of cases there was histocompatibility between the cord cell and the receptors. Transplantation was done in 87 patients, 67% had hematologic neoplasias, who have received 140 units of UCB in 102 transplants. This Bank of UCB ranks second in the world in productivity according to the rate of utility of units in transplantation (3.3%). Our bank of UCB has been able to develop a cell line (hematopoietic stem cells) with international quality standards and has been beneficial for patients served by our institution with need of a transplant mainly in hemato-oncologic patients.

Cord blood clinical processing, cryopreservation, and storage.

PubMed

Elmoazzen, Heidi; Holovati, Jelena L

2015-01-01

Allogeneic umbilical cord blood (UCB) hematopoietic stem cell transplantation has become a crucial advancement in the treatment for a variety of diseases including hematopoietic and non-hematopoietic malignancies, BM failure syndromes, hemoglobinopathies, and metabolic and immunodeficiency disorders. It has been well documented that the success of UCB engraftment is tied to UCB banking processes, and now there are established guidelines for standardization of collection, banking, processing, and cryopreservation for unrelated UCB units with purpose of achieving consistent production of high quality placental and UCB units for administration. In 2011, Canada's Ministry of Health has announced Canada's first national, publicly funded umbilical cord blood bank, which aims to provide altruistic donations for unrelated allogeneic hematopoietic stem cell transplant. In this chapter, we describe specific protocols for clinical processing, cryopreservation, and storage of UCB used by the Canadian Blood Services National Public Umbilical Cord Blood Bank.

Stem-Cell Therapy Advances in China.

PubMed

Hu, Lei; Zhao, Bin; Wang, Songlin

2018-02-01

Stem-cell therapy is a promising method for treating patients with a wide range of diseases and injuries. Increasing government funding of scientific research has promoted rapid developments in stem-cell research in China, as evidenced by the substantial increase in the number and quality of publications in the past 5 years. Multiple high-quality studies have been performed in China that concern cell reprogramming, stem-cell homeostasis, gene modifications, and immunomodulation. The number of translation studies, including basic and preclinical investigations, has also increased. Around 100 stem-cell banks have been established in China, 10 stem-cell drugs are currently in the approval process, and >400 stem cell-based clinical trials are currently registered in China. With continued state funding, advanced biotechnical support, and the development of regulatory standards for the clinical application of stem cells, further innovations are expected that will lead to a boom in stem-cell therapies. This review highlights recent achievements in stem-cell research in China and discusses future prospects.

Umbilical cord cell banking-implications for the future

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunning, Jennifer

2005-09-01

The first successful cord cell transplant to a sibling with Fanconi's anaemia took place 15 years ago. This proven utility of cord blood led to the establishment of cord blood banks both private and public and there are now nearly 100 cord blood banks worldwide. It is estimated that over 200,000 cord blood units (CBU) are held by the private sector and over 160,000 CBU are registered with the largest public cord blood registry. There is a tension between private cord blood banks, which store CBU for autologous or family use, and public banks, which store CBU for unrelated usemore » and the ethics of private cord blood storage has been questioned. But more general ethical questions also arise regarding ownership, consent, confidentiality, costs and quality standards and patenting. In looking at these ethical issues one also needs to look at potential future use of cord blood stem cells. Up until now cord cells have principally been used in the treatment of paediatric blood and immune disorders. Improvements in cell expansion technology will make CBU more appropriate also for treating adults with such disorders. However, it has also been demonstrated that cord blood stem cells have the capacity to differentiate into other types of cells, neuronal, bone, epithelial and muscle which would have a future role to play in cell therapy and regenerative medicine.« less

Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells.

PubMed

Stephenson, Emma; Ogilvie, Caroline Mackie; Patel, Heema; Cornwell, Glenda; Jacquet, Laureen; Kadeva, Neli; Braude, Peter; Ilic, Dusko

2010-12-06

The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources.

A Review of Factors Influencing the Banking of Collected Umbilical Cord Blood Units

PubMed Central

Allan, David; Petraszko, Tanya; Elmoazzen, Heidi; Smith, Susan

2013-01-01

Umbilical cord blood banking efforts have increased dramatically in the past two decades in response to increasing demand for alternative sources of blood stem cells to support patients requiring hematopoietic stem cell transplantation. Transplant centres have accumulated increasing expertise in their understanding of umbilical cord blood characteristics that are associated with improved outcome following transplantation. These characteristics and factors can assist transplant centres in selecting cord blood units from the worldwide inventory of banked units. Umbilical cord blood banks, therefore, need to remain agile in adjusting the inventory of the banks to address shifts or changes in the needs of transplant centres. Public umbilical cord blood banks face the challenge of building inventory while managing limited resources and are faced with decisions regarding which units can be stored and which units that have been collected should be discarded or used for other endeavours such as research. To this end, we sought to review parameters influencing the decision to bank a collected cord blood unit. In this paper, we will address parameters associated with graft potency and address other factors that guide the decision to bank collected units. PMID:23533442

Therapeutic potential of dental stem cells

PubMed Central

Chalisserry, Elna Paul; Nam, Seung Yun; Park, Sang Hyug; Anil, Sukumaran

2017-01-01

Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells. Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells. Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. The dental stem cells represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies. The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart. The concept of developing tooth banking and preservation of dental stem cells is promising. Further research in the area has the potential to herald a new dawn in effective treatment of notoriously difficult diseases which could prove highly beneficial to mankind in the long run. PMID:28616151

Low usage rate of banked sibling cord blood units in hematopoietic stem cell transplantation for children with hematological malignancies: implications for directed cord blood banking policies.

PubMed

Goussetis, Evgenios; Peristeri, Ioulia; Kitra, Vasiliki; Papassavas, Andreas C; Theodosaki, Maria; Petrakou, Eftichia; Spiropoulos, Antonia; Paisiou, Anna; Soldatou, Alexandra; Stavropoulos-Giokas, Catherine; Graphakos, Stelios

2011-02-15

Directed sibling cord blood banking is indicated in women delivering healthy babies who already have a sibling with a disease that is potentially treatable with an allogeneic cord blood transplant. We evaluated the effectiveness of a national directed cord blood banking program in sibling HLA-identical stem cell transplantation for hematological malignancies and the factors influencing the usage rate of the stored cord blood units. Fifty families were enrolled from which, 48 cord blood units were successfully collected and 2 collections failed due to damaged cord/placenta at delivery. Among enrolled families 4 children needed transplantation; however, only one was successfully transplanted using the collected cord blood unit containing 2×10(7) nucleated cells/kg in conjunction with a small volume of bone marrow from the same HLA-identical donor. Two children received grafts from matched unrelated donors because their sibling cord blood was HLA-haploidentical, while the fourth one received bone marrow from his HLA-identical brother, since cord blood could not be collected due to damaged cord/placenta at delivery. With a median follow-up of 6 years (range, 2-12) for the 9 remaining HLA-matched cord blood units, none from the prospective recipients needed transplantation. The low utilization rate of sibling cord blood in the setting of hematopoietic stem cell transplantation for pediatric hematological malignant diseases necessitates the development of directed cord blood banking programs that limit long-term storage for banked cord blood units with low probability of usage such as non-HLA-identical or identical to patients who are in long-term complete remission. Copyright © 2010 Elsevier Inc. All rights reserved.

Human mesenchymal stem cells: a bank perspective on the isolation, characterization and potential of alternative sources for the regeneration of musculoskeletal tissues.

PubMed

Moroni, Lorenzo; Fornasari, Pier Maria

2013-04-01

The continuous discovery of human mesenchymal stem cells (hMSCs) in different tissues is stirring up a tremendous interest as a cell source for regenerative medicine therapies. Historically, hMSCs have been always considered a sub-population of mononuclear cells present in the bone marrow (BM). Although BM-hMSCs are still nowadays considered as the most promising mesenchymal stem cell population to reach the clinics due to their capacity to differentiate into multiple tissues, hMSCs derived from other adult and fetal tissues have also demonstrated to possess similar differentiation capacities. Furthermore, different reports have highlighted a higher recurrence of hMSCs in some of these tissues as compared to BM. This offer a fascinating panorama for cell banking, since the creation of a stem cell factory could be envisioned where hMSCs are stocked and used for ad hoc clinical applications. In this review, we summarize the main findings and state of the art in hMSCs isolation, characterization, and differentiation from alternative tissue sources and we attempt to compare their potency for musculoskeletal regeneration. Copyright © 2012 Wiley Periodicals, Inc.

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England.

PubMed

Busby, Helen

2010-03-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public 'cord blood bank', for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed.

The science of stem cell biobanking: investing in the future.

PubMed

Diaferia, Giuseppe R; Cardano, Marina; Cattaneo, Monica; Spinelli, Chiara C; Dessì, Sara S; DeBlasio, Pasquale; Biunno, Ida

2012-01-01

The use of human stem cells in biomedical research projects is increasing steadily and the number of cells that are being derived develops at a remarkable pace. However, stem cells around the world are vastly different in their provenance, programming, and potentials. Furthermore, knowledge on the actual number of cell types, their derivation, availability, and characteristics is rather sparse. Usually, "colleague-supply" avenues constantly furnish cells to laboratories around the world without ensuring their correct identity, characterization, and quality. These parameters are critical if the cells will be eventually used in toxicology studies and drug discovery. Here, we outline some basic principles in establishing a stem cell-specific bank. Copyright © 2011 Wiley Periodicals, Inc.

Bioprocessing of Cryopreservation for Large-Scale Banking of Human Pluripotent Stem Cells

PubMed Central

Ma, Teng

2012-01-01

Abstract Human pluripotent stem cell (hPSC)-derived cell therapy requires production of therapeutic cells in large quantity, which starts from thawing the cryopreserved cells from a working cell bank or a master cell bank. An optimal cryopreservation and thaw process determines the efficiency of hPSC expansion and plays a significant role in the subsequent lineage-specific differentiation. However, cryopreservation in hPSC bioprocessing has been a challenge due to the unique growth requirements of hPSC, the sensitivity to cryoinjury, and the unscalable cryopreservation procedures commonly used in the laboratory. Tremendous progress has been made to identify the regulatory pathways regulating hPSC responses during cryopreservation and the development of small molecule interventions that effectively improves the efficiency of cryopreservation. The adaption of these methods in current good manufacturing practices (cGMP)-compliant cryopreservation processes not only improves cell survival, but also their therapeutic potency. This review summarizes the advances in these areas and discusses the technical requirements in the development of cGMP-compliant hPSC cryopreservation process. PMID:23515461

Umbilical cord blood banking: implications for perinatal care providers.

PubMed

Armson, B Anthony

2005-03-01

To evaluate the risks and benefits of umbilical cord blood banking for future stem cell transplantation and to provide guidelines for Canadian perinatal care providers regarding the counselling, procedural, and ethical implications of this potential therapeutic option. Selective or routine collection and storage of umbilical cord blood for future autologous (self) or allogenic (related or unrelated) transplantation of hematopoietic stem cells to treat malignant and nonmalignant disorders in children and adults. Maternal and perinatal morbidity, indications for umbilical cord blood transplantation, short- and long-term risks and benefits of umbilical cord blood transplantation, burden of umbilical cord blood collection on perinatal care providers, parental satisfaction, and health care costs. MEDLINE and PubMed searches were conducted from January 1970 to October 2003 for English-language articles related to umbilical cord blood collection, banking, and transplantation; the Cochrane library was searched; and committee opinions of the Royal College of Obstetricians and Gynaecologists, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists were obtained. The evidence collected was reviewed and evaluated by the Maternal/Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), and recommendations were made using the evaluation of evidence guidelines developed by the Canadian Task Force on the Periodic Health Exam. Umbilical cord blood is a readily available source of hematopoietic stem cells used with increasing frequency as an alternative to bone marrow or peripheral stem cells for transplantation in the treatment of malignant and nonmalignant conditions in children and adults. Umbilical cord blood transplantation provides a rich source of hematopoietic stem cells with several advantages, including prompt availability, decreased risk of transmissible viral infections and graft-versus-host disease (GVHD) in both human leukocyte antigen(HLA)-matched and HLA-mismatched stem cell transplants, and ease of collection with little risk to the mother or newborn. Potential limitations of umbilical cord blood transplantation include insufficient stem cell dose to reliably treat larger children and adult recipients, slower rate of engraftment, and the potential for transfer of genetically abnormal hematopoietic stem cells. The optimum method of umbilical cord blood transplantation is not yet clear, though available evidence would favour collection before delivery of the placenta. There are many unresolved ethical issues related to umbilical cord blood banking, particularly related to the rapid growth of private, for-profit, cord blood banks offering long-term storage for potential future autologous or related allogenic transplantation. The financial burden to the health care system for public cord blood banking and to families for private cord blood collection and storage is considerable. 1. Perinatal care providers should be informed about the promising clinical potential of hematopoietic stem cells in umbilical cord blood and about current indications for its collection, storage, and use, based on sound scientific evidence (II-3B). 2. Umbilical cord blood collection should be considered for a sibling or parent in need of stem cell transplantation when an HLA-identical bone marrow cell or peripheral stem cell donation from a sibling or parent is unavailable for transplantation (II-2B). 3. Umbilical cord blood should be considered when allogeneic transplantation is the treatment of choice for a child who does not have an HLA-identical sibling or a well-matched, unrelated adult bone marrow donor (II-2B). 4. Umbilical cord blood should be considered for allogeneic transplantation in adolescents and young adults with hematologic malignancies who have no suitable bone marrow donor and who require urgent transplantation (II-3B). 5. Altruistic donation of cord blood for public banking and subsequent allogeneic transplantation should be encouraged when umbilical cord blood banking is being considered by childbearing women, prenatal care providers, and(or) obstetric facilities (II-2B). 6. Collection and long-term storage of umbilical cord blood for autologous donation is not recommended because of the limited indications and lack of scientific evidence to support the practice (III-D). 7. Birth unit staff should receive training in standardized cord blood unit volume and reduce the rejection rate owing to labelling problems, bacterial contamination, and clotting (II-3B). 8. The safe management of obstetric delivery should never be compromised to facilitate cord blood collection. Manoeuvres to optimize cord blood unit volume, such as early clamping of the umbilical cord, may be employed at the discretion of the perinatal care team, provided the safety of the mother and newborn remains the major priority (III-A). 9. Collection of cord blood should be performed after the delivery of the infant but before delivery of the placenta, using a closed collection system and procedures that minimize risk of bacterial and maternal fluid contamination (see Figures 1a-1c) (I-B). 10. Public and private cord blood banks should strictly adhere to standardized policies and procedures for transportation, safety testing, HLA typing, cryopreservation, and long-term storage of umbilical cord blood units to prevent harm to the recipient, to eliminate the risk of transmitting communicable diseases, and thus to maximize the effectiveness of umbilical cord blood stem cell transplantation (II-1A). 11. Canada should establish registration, regulation, and accreditation of cord blood collection centres and banks (III-B). 12. Recruitment of cord blood donors should be fair and noncoercive. Criteria to ensure an equitable recruitment process include the following: (a) adequate supply to meet population transplantation needs; (b) fair distribution of the burdens and benefits of cord blood collection; (c) optimal timing of recruitment; (d) appropriately trained personnel; and (e) accurate recruitment message (III-A). 13. Informed consent for umbilical cord blood collection and banking should be obtained during prenatal care, before the onset of labour, with confirmation of consent after delivery (III-B). 14. Linkage of cord blood units and donors is recommended for public safety. Policies regarding the disclosure of abnormal test results to donor parents should be developed. Donor privacy and confidentiality of test results must be respected (III-C). 15. Commercial cord blood banks should be carefully regulated to ensure that promotion and pricing practices are fair, financial relationships are transparent, banked cord blood is stored and used according to approved standards, and parents and care providers understand the differences between autologous versus allogenic donations and private versus public banks (III-B). 16. Policies and procedures need to be developed by perinatal facilities and national health authorities to respond to prenatal requests for public and private cord blood banking (III-C).

Redefining the potential applications of dental stem cells: An asset for future

PubMed Central

Rai, Shalu; Kaur, Mandeep; Kaur, Sandeep; Arora, Sapna Panjwani

2012-01-01

Recent exciting discoveries isolated dental stem cells from the pulp of the primary and permanent teeth, from the periodontal ligament, and from associated healthy tissues. Dental pulp stem cells (DPSCs) represent a kind of adult cell colony which has the potent capacity of self-renewing and multilineage differentiation. Stem cell-based tooth engineering is deemed as a promising approach to the making of a biological tooth (bio-tooth) or engineering of functional tooth structures. Dental professionals have the opportunity to make their patients aware of these new sources of stem cells that can be stored for future use as new therapies are developed for a range of diseases and injuries. The aim of this article is to review and understand how dental stem cells are being used for regeneration of oral and conversely nonoral tissues. A brief review on banking is also done for storing of these valuable stem cells for future use. PMID:23716933

Human cord blood applications in cell therapy: looking back and look ahead.

PubMed

Zhou, Hongyan; Chang, Stephen; Rao, Mahendra

2012-08-01

Human umbilical cord blood (UCB) has been used as a reliable source of stem cells for blood-borne diseases and disorders. Recent advances in cell reprogramming technology to produce induced pluripotent stem (iPS) cells, which can be differentiated to multiple adult cell types, has further expanded the potential of cord blood cell therapy for treatment of non-blood-borne diseases. However, in order to harness this breakthrough technology and to provide clinical-grade cells for the patient, standardization of iPS production and differentiation, and good manufacturing practice (GMP) need to be employed. UCB is an ethical source of stem cells and has been used to treat diseases including leukemia, cancer and blood disorders. The development of iPS cell technology could potentially greatly increase the application of cord blood cells as a treatment for a broader range of diseases, UCB-iPS banks could, therefore, be a valuable complementary source of clinical-grade cells for cell therapy. The current applicability of GMP to UCB and UCB-iPS cell-based cell therapy will be discussed. Although cord blood stem cell therapies have been practiced for decades, UCB-iPS cell therapies are a new innovation currently in development. Successful clinical applications of such novel cell therapies will depend on the production of GMP-compliant cells and the establishment of cell banks.

Regulatory Insight into the European Human Pluripotent Stem Cell Registry

PubMed Central

Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

2014-01-01

Abstract The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders. PMID:25457963

Regulatory insight into the European human pluripotent stem cell registry.

PubMed

Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

2014-12-01

The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders.

Institutional Knots: A Comparative Analysis of Cord Blood Policy in Canada and the United States.

PubMed

Denburg, Avram

2016-02-01

Umbilical cord blood is a rich source of blood stem cells, which are of critical clinical importance in the treatment of a variety of malignant and genetic conditions requiring stem cell transplantation. Many countries have established national public cord blood banks; such banks often coexist with a panoply of private options for cord blood banking. Until recently, Canada was the only G8 country without a national cord blood bank. This differs markedly from the United States, which years ago established a national cord blood bank policy and inventory. This article investigates potential reasons for this discrepancy through a comparative analysis of the evolution of programs and policies on national cord blood banking in Canada and the United States. My analysis suggests that cross-national discrepancies in policy on public cord blood banking were determined primarily by institutional factors, principal among them formal governmental structure and the legacy of past policies. Institutional entrepreneurialism in the health sector played a constitutive role in the earlier evolution of national cord blood policy in the United States as compared to Canada. Copyright © 2016 by Duke University Press.

Clinical application of adipose stem cells in plastic surgery.

PubMed

Kim, Yong-Jin; Jeong, Jae-Ho

2014-04-01

Adipose stem cells (ASCs) are a type of adult stem cells that share common characteristics with typical mesenchymal stem cells. In the last decade, ASCs have been shown to be a useful cell resource for tissue regeneration. The major role of regenerative medicine in this century is based on cell therapy in which ASCs hold a key position. Active research on this new type of adult stem cell has been ongoing and these cells now have several clinical applications, including fat grafting, overcoming wound healing difficulties, recovery from local tissue ischemia, and scar remodeling. The application of cultured cells will increase the efficiency of cell therapy. However, the use of cultured stem cells is strictly controlled by government regulation to ensure patient safety. Government regulation is a factor that can limit more versatile clinical application of ASCs. In this review, current clinical applications of ASCs in plastic surgery are introduced. Future stem cell applications in clinical field including culturing and banking of ASCs are also discussed in this review.

Cord stem-cell transplantation in Ontario: do we need a public bank?

PubMed

Gassas, A

2011-06-01

It has been 21 years since the first successful use of umbilical cord blood as a source of donor cells for hematopoietic stem cell transplantation (HSCT). Over those years, cord blood transplantation (CBT) has shown marked success as an effective modality in the treatment of children and adults with hematologic malignancies, marrow failure, immunodeficiency, hemoglobinopathy, and inherited metabolic diseases. Furthermore, transplantation without full human leukocyte antigen (HLA) matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia effect is preserved. More than 20,000 cbts have been performed worldwide. Ontario is the most populated province in Canada, and its cbt numbers have increased dramatically in recent years, but most of the umbilical cord blood units are purchased from unrelated international registries. There is no public cord bank in Ontario, but there is a private cord banking option, and notably, Ontario has the largest number of live births in Canada [approximately 40% of all Canadian live births per year occur in Ontario (Statistics Canada, 2007)]. In this brief review, the pros and cons of private and public cord banking and the feasibility of starting an Ontario public cord bank are discussed.

Adult Stem Cell Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

DTIC Science & Technology

2016-10-01

isolated stem cells from the injured tissue site that have wound healing promoting activities. In this application, we propose to use these cells, which may...Regeneration, Nanofiber, Neurotrophic Factor, Tissue Engineering, Multifunctional 3. ACCOMPLISHMENTS:  The major goals of this project are...have been stored in cell bank . Objective 9: Purchase reagents and materials for methacrylation of ECM hydrogel  All necessary reagents and

Generation of human induced pluripotent stem cells from urinary cells of a healthy donor using a non-integration system.

PubMed

Uhm, Kyung-Ok; Jo, Eun Hee; Go, Gue Youn; Kim, So-Jung; Choi, Hye Young; Im, Young Sam; Ha, Hye-Yeong; Jung, Ji-Won; Koo, Soo Kyung

2017-05-01

Urinary cells can be an ideal source for generating hiPSCs and progenitors, as they are easily accessible, non-invasive, and universally available. We generated human induced pluripotent stem cells (hiPSCs) from the urinary cells of a healthy donor using a Sendai virus-based gene delivery method. The generated hiPSC line, KSCBi001-A, has a normal karyotype (46,XY). The pluripotency and capacity of multilineage differentiation were characterized by comparison with those of a human embryonic stem cell line. This cell line is registered and available from National Stem Cell Bank, Korea National Institute of Health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Progeria 101/FAQ

MedlinePlus

... Culture Protocols Immortalized Cell Culture Protocols Induced Pluripotent Stem Cells PRF Cell and Tissue Bank Publications Research Funding Opportunities Grant Application Application Deadlines Grants Funded Close Meet The Kids Meet The Kids Our Ambassadors Find The Other ...

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

PubMed

Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

2013-08-01

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

[The bioethics law revision: comparative analysis of contributions from different public and professional offices. Assisted Reproductive Technology, embryo and stem cells research, umbilical cord blood bank].

PubMed

Merviel, P; Cabry, R; Lourdel, E; Brasseur, F; Devaux, A; Copin, H

2009-09-01

The revision of the bioethics law of 2004 must occur in a five year's time. For this revision, the authorities decided to organize general states of bioethics and requested the production of contributions by the companies, institutions or associations. These texts tackle various subjects, like the Assisted Reproductive Technologies, research on the embryo and the stem cells and the banks of umbilical cord blood. Certain opinions converge, others differ, but all take part in the great debate which will take place at the time of the general conference.

Progeria Research Foundation Diagnostic Testing Program

MedlinePlus

... Culture Protocols Immortalized Cell Culture Protocols Induced Pluripotent Stem Cells PRF Cell and Tissue Bank Publications Research Funding Opportunities Grant Application Application Deadlines Grants Funded Close Meet The Kids Meet The Kids Our Ambassadors Find The Other ...

Selection of Phage Display Peptides Targeting Human Pluripotent Stem Cell-Derived Progenitor Cell Lines.

PubMed

Bignone, Paola A; Krupa, Rachel A; West, Michael D; Larocca, David

2016-01-01

The ability of human pluripotent stem cells (hPS) to both self-renew and differentiate into virtually any cell type makes them a promising source of cells for cell-based regenerative therapies. However, stem cell identity, purity, and scalability remain formidable challenges that need to be overcome for translation of pluripotent stem cell research into clinical applications. Directed differentiation from hPS cells is inefficient and residual contamination with pluripotent cells that have the potential to form tumors remains problematic. The derivation of scalable (self-renewing) embryonic progenitor stem cell lines offers a solution because they are well defined and clonally pure. Clonally pure progenitor stem cell lines also provide a means for identifying cell surface targeting reagents that are useful for identification, tracking, and repeated derivation of the corresponding progenitor stem cell types from additional hPS cell sources. Such stem cell targeting reagents can then be applied to the manufacture of genetically diverse banks of human embryonic progenitor cell lines for drug screening, disease modeling, and cell therapy. Here we present methods to identify human embryonic progenitor stem cell targeting peptides by selection of phage display libraries on clonal embryonic progenitor cell lines and demonstrate their use for targeting quantum dots (Qdots) for stem cell labeling.

Umbilical cord blood: a guide for primary care physicians.

PubMed

Martin, Paul L; Kurtzberg, Joanne; Hesse, Brett

2011-09-15

Umbilical cord blood stem cell transplants are used to treat a variety of oncologic, genetic, hematologic, and immunodeficiency disorders. Physicians have an important role in educating, counseling, and offering umbilical cord blood donation and storage options to patients. Parents may donate their infant's cord blood to a public bank, pay to store it in a private bank, or have it discarded. The federal government and many state governments have passed laws and issued regulations regarding umbilical cord blood, and some states require physicians to discuss cord blood options with pregnant women. Five prominent medical organizations have published recommendations about cord blood donation and storage. Current guidelines recommend donation of umbilical cord blood to public banks when possible, or storage through the Related Donor Cord Blood Program when a sibling has a disease that may require a stem cell transplant. Experts do not currently recommend private banking for unidentified possible future use. Step-by-step guidance and electronic resources are available to physicians whose patients are considering saving or donating their infant's umbilical cord blood.

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England

PubMed Central

Busby, Helen

2010-01-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public ‘cord blood bank’, for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed. PMID:21666742

Private Cord Blood Banking: Experiences And Views Of Pediatric Hematopoietic Cell Transplantation Physicians

PubMed Central

Thornley, Ian; Eapen, Mary; Sung, Lillian; Lee, Stephanie J.; Davies, Stella M.; Joffe, Steven

2011-01-01

Objective Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation (HCT) physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. Participants and Methods Emailed cross-sectional survey of pediatric HCT physicians in the United States and Canada. 93/152 potentially eligible physicians (93/130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. Results Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36/40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alternative stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with one healthy sibling when both parents were of Northern European descent; 11% would recommend banking when parents were of different minority ethnicities. Conclusions Few transplants have been performed using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric HCT physicians endorse private cord blood banking in the absence of an identified recipient, even for mixed-ethnicity children for whom finding a suitably matched unrelated donor may be difficult. PMID:19255033

Experiences of the Dresdner Cord Blood Bank, supported by the Deutsche Knochenmarkspenderdatei.

PubMed

Ordemann, R; Petzold, K; Hölig, K; Schaffer, B; Mauersberger, S; Ehninger, G; Ehminger, G

1999-01-01

Allogeneic bone marrow and peripheral blood stem cell transplantation is the treatment of choice for some malignant hematologic diseases, marrow failure syndromes, and severe congenital immunodeficiency states. Since Gluckman et al reported in 1988 the first successful human leukocyte antigen (HLA)-matched sibling umbilical cord blood stem cell transplantation, it has been known that cord blood is a valuable source of hematopoietic stem cells. The Cord Blood Bank at the University Hospital of Dresden was founded in 1997 and started collecting, processing, and cryoconserving umbilical cord blood in August 1997. The cord blood bank is supported by the largest German donor registry: Deutsche Knochenmarkspenderdatei (DKMS) in Tubingen, Germany. With the informed consent of the mothers, the collection is performed in collaboration with six hospitals in Dresden, Berlin, and Bautzen. We routinely perform a volume reduction by centrifuging the blood bag and expressing the leukocyte-rich supernatant. Routinely, sterility, total nucleated cells (TNC), CD34+ cell count, HLA class I and II, ABO/Rh blood group, and colony-forming units are evaluated. The maternal blood is screened for anti-immunodeficiency virus (anti-HIV), anti-hepatitis C virus (anti-HCV), anti-hepatitis B surface antigen (HBsAg), anti-hepatitis B surface (anti-HBs), anti-hepatitis B core (anti-HBc), anticytomegalovirus (anti-CMV), and toxoplasmosis and with Treponema pallidum hemagglutination assay (TPHA). More than 1,000 cord blood units could be collected. Because of the required volume and cell count and because of sterility, 50% of the collected units had to be discharged. Our results are comparable with data of other cord blood banks: mean volume 79 mL; cell count after volume reduction-TNC, 7.16 x 10(8); mononucleated cells (MNC), 3.75 x 10(8); CD34+ cells, 1.95 x 10(6); colony-forming units (CFU), 67.1 x 10(4). To increase the pool of potential umbilical cord blood units and in order to evaluate the possibility for unrelated transplants, cryopreservation and banking of large numbers of cord bloods are necessary.

US public cord blood banking practices: recruitment, donation, and the timing of consent.

PubMed

Broder, Sherri M; Ponsaran, Roselle S; Goldenberg, Aaron J

2013-03-01

Cord blood has moved rapidly from an experimental stem cell source to an accepted and important source of hematopoietic stem cells. There has been no comprehensive assessment of US public cord blood banking practices since the Institute of Medicine study in 2005. Of 34 US public cord blood banks identified, 16 participated in our qualitative survey of public cord blood banking practices. Participants took part in in-depth telephone interviews in which they were asked structured and open-ended questions regarding recruitment, donation, and the informed consent process at these banks. Thirteen of 16 participants reported a variably high percentage of women who consented to public cord blood donation. Fifteen banks offered donor registration at the time of hospital admission for labor and delivery. Seven obtained full informed consent and medical history during early labor and eight conducted some form of phased consent and/or phased medical screening and history. Nine participants identified initial selection of the collection site location as the chief mode by which they recruited minority donors. Since 2005, more public banks offer cord blood donor registration at the time of admission for labor and delivery. That and the targeted location of cord blood collection sites are the main methods used to increase access to donation and HLA diversity of banked units. Currently, the ability to collect and process donations, rather than donor willingness, is the major barrier to public cord blood banking. © 2012 American Association of Blood Banks.

Banking cord blood stem cells: attitude and knowledge of pregnant women in five European countries.

PubMed

Katz, Gregory; Mills, Antonia; Garcia, Joan; Hooper, Karen; McGuckin, Colin; Platz, Alexander; Rebulla, Paolo; Salvaterra, Elena; Schmidt, Alexander H; Torrabadella, Marta

2011-03-01

This study explores pregnant women's awareness of cord blood stem cells and their attitude regarding banking options in France, Germany, Italy, Spain, and the UK. Questionnaires were distributed in six maternities. This anonymous and self-completed questionnaire included 29 multiple-choice questions based on: 1) sociodemographic factors, 2) awareness and access to information about cord blood banking, 3) banking option preferences, and 4) donating cord blood units (CBUs) to research. A total of 79% of pregnant women had little awareness of cord blood banking (n = 1620). A total of 58% of women had heard of the therapeutic benefits of cord blood, of which 21% received information from midwives and obstetricians. A total of 89% of respondents would opt to store CBUs. Among them, 76% would choose to donate CBUs to a public bank to benefit any patient in need of a cord blood transplant. Twelve percent would choose a mixed bank, and 12%, a private bank. A total of 92% would donate their child's CBU to research when it is not suitable for transplantation. The study reveals a strong preference for public banking in all five countries, based on converging values such as solidarity. Attitudes of pregnant women are not an obstacle to the rapid expansion of allogeneic banking in these EU countries. Banking choices do not appear to be correlated with household income. The extent of commercial marketing of cord blood banks in mass media highlights the importance for obstetric providers to play a central role in raising women's awareness early during their pregnancy with evidence-based medical information about banking options. © 2010 American Association of Blood Banks.

Biobanking of Human Retinas: The Next Big Leap for Eye Banks?

PubMed Central

Lužnik, Zala; Parekh, Mohit; Bertolin, Marina; Griffoni, Carlo; Ponzin, Diego

2015-01-01

Summary Retinal degenerative diseases are one of the main clinical causes of incurable and severe visional impairment. Thus, extensive research effort is put into the development of new causal therapeutic options. Promisingly, a number of studies showed regenerative capacity in specific retinal regions (the ciliary epithelium, retinal pigmented epithelium, iris, and Müller glia cells). However, most recent research studies are based on animal models or in vitro cultured cells, probably because of the limited availability of human posterior eye tissues (vitreous, retina, and choroid). To address this, we showed in our previous reports that eye banks with large numbers of globes collected yearly could set up biorepositories/biobanks where these precious tissues are isolated, quality controlled, and finally stored for scientists and clinicians wanting to access human tissues and test their own hypotheses. These precious human posterior eye tissues could be used for further research purposes, epidemiological studies, and target validation of newly developed drugs. In addition, this could be a promising and challenging option to retrieve potential retinal stem and progenitor cells from different parts of the retina and could be a breakthrough in the future delivery of ex vivo prepared customized (histocompatible) retinal tissue on scaffolds for transplantation purposes. In this Perspective, we will consider how the biorepositories could influence the future strategies for retinal stem cell therapies. Significance Retinal degenerative diseases are one of the main causes of severe vision impairment and regenerative medicine is attracting much attention as a potential therapy. Although highly desirable, the reactivation and proliferation of endogenous stem cells in vivo is not sufficient to generate enough cells to restore visual function after retinal injury. Thus, the replacement of exogenously derived normal donor cells is a promising solution. The challenge is to develop therapies with sufficient amounts of cells being harvested or expanded from donor tissues. Eye banks could overcome this issue by harvesting endogenous adult retinal stem cells from different donors. PMID:26032747

US Public Cord Blood Banking Practices: Recruitment, Donation, and the Timing of Consent

PubMed Central

Broder, Sherri; Ponsaran, Roselle; Goldenberg, Aaron

2012-01-01

BACKGROUND Cord blood has moved rapidly from an experimental stem cell source to an accepted and important source of hematopoietic stem cells. There has been no comprehensive assessment of US public cord blood banking practices since the Institute of Medicine study in 2005. STUDY DESIGN AND METHODS Of 34 US public cord blood banks identified, 16 participated in our qualitative survey of public cord blood banking practices. Participants took part in in-depth telephone interviews in which they were asked structured and open-ended questions regarding recruitment, donation, and the informed consent process at these banks. RESULTS 13 of 16 participants reported a variably high percentage of women who consented to public cord blood donation. 15 banks offered donor registration at the time of hospital admission for labor and delivery. 7 obtained full informed consent and medical history during early labor and 8 conducted some form of phased consent and/or phased medical screening and history. 9 participants identified initial selection of the collection site location as the chief mode by which they recruited minority donors. CONCLUSION Since 2005, more public banks offer cord blood donor registration at the time of admission for labor and delivery. That, and the targeted location of cord blood collection sites, are the main methods used to increase access to donation and HLA diversity of banked units. Currently, the ability to collect and process donations, rather than donor willingness, is the major barrier to public cord blood banking. PMID:22803637

Investigating the mincing method for isolation of adipose-derived stem cells from pregnant women fat.

PubMed

Li, Yuan-Sheng; Chen, Pao-Jen; Wu, Li-Wei; Chou, Pei-Wen; Sun, Li-Yi; Chiou, Tzyy-Wen

2018-02-01

The success of stem cell application in regenerative medicine, usually require a stable source of stem or progenitor cells. Fat tissue represents a good source of stem cells because it is rich in stem cells and there are fewer ethical issues related to the use of such stem cells, unlike embryonic stem cells. Therefore, there has been increased interest in adipose-derived stem cells (ADSCs) for tissue engineering applications. Here, we aim to provide an easy processing method for isolating adult stem cells from human adipose tissue harvested from the subcutaneous fat of the abdominal wall during gynecologic surgery. We used a homogenizer to mince fat and compared the results with those obtained from the traditional cut method involving a sterile scalpel and forceps. Our results showed that our method provides another stable and quality source of stem cells that could be used in cases with a large quantity of fat. Furthermore, we found that pregnancy adipose-derived stem cells (P-ADSCs) could be maintained in vitro for extended periods with a stable population doubling and low senescence levels. P-ADSCs could also differentiate in vitro into adipogenic, osteogenic, chondrogenic, and insulin-producing cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirates, adipose tissues obtained from pregnant women contain multipotent cells with better proliferation and showed great promise for use in both stem cell banking studies as well as in stem cell therapy.

Tissue procurement system in Japan: the role of a tissue bank in medical center for translational research, Osaka University Hospital.

PubMed

Ohkawara, H; Fukushima, N; Kitagawa, T; Ito, T; Masutani, Y; Sawa, Y

2010-01-01

Although organ procurement has been regulated by The Organ Transplantation Law (brain-dead donors since 1997, donors after cardiac death since 1979), there has been no law or governmental procurement network (except for cornea) in Japan. Since the late 1980s, some university hospitals have developed original banks. Finally, in 2001 guidelines for tissue procurement were established by The Japanese Society of Tissue Transplantation and Japan Tissue Transplant Network (JTTN) to coordinate tissue harvesting. Five tissue banks were joined to the tissue transplant network (skin in one, heart valves in two, and bone in two). As the number of tissue banks is small, each bank cooperates on procurement, but cannot cover the entire country. With regard to skin transplantation, only one skin bank-The Japan Skin Bank Network (JSBN), which is located in Tokyo-has organized skin procurement. Therefore, it has been difficult to procure skin in areas distant from Tokyo, especially around Osaka. In order to improve such a situation, a tissue bank collaborating with the JSBN was established at The Medical Center for Translational Research (MTR), Osaka University Hospital in April 2008. The bank has played a role in skin procurement center in western Japan and supported procurement and preservation at the time of the skin procurement. Between April 2008 and September 2009, the bank participated in eight tissue procurements in the western area. In the future, the bank is planning to procure and preserve pancreatic islets and bones. Moreover, there is a plan to set up an induced pluripotent stem cells center and stem cell bank in MTR. This tissue bank may play a role to increase tissue procurement in Japan, especially in the western area. .

Time related variations in stem cell harvesting of umbilical cord blood

NASA Astrophysics Data System (ADS)

Mazzoccoli, Gianluigi; Miscio, Giuseppe; Fontana, Andrea; Copetti, Massimiliano; Francavilla, Massimo; Bosi, Alberto; Perfetto, Federico; Valoriani, Alice; de Cata, Angelo; Santodirocco, Michele; Totaro, Angela; Rubino, Rosa; di Mauro, Lazzaro; Tarquini, Roberto

2016-02-01

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units.

[THE USE AND STORAGE OF STEM CELLS AND CORD BLOOD: FRENCH AND ENGLISH LAW COMPARATIVE APPROACH].

PubMed

Madanamoothoo, Allane

2015-07-01

Becoming parents is one of the greatest wishes of a lot of couples. When their dreams come true, prior to the birth of the child, parents have to face several points: the choice of the name, place of delivery, breast or bottle feeding, etc. Recently, they have to face the issues of cord blood stem cells. Researchers and cord blood banks are also interested in those cells. In many countries a lot of advertising is made around umbilical cord blood stem cells. In France as in England, the use and preservation of cord blood are regulated by the legislators without necessarily having the same approach. The objective of this paper is to present English and French law approaches' on cord blood stem cells.

Stem cell applications in military medicine.

PubMed

Christopherson, Gregory T; Nesti, Leon J

2011-10-19

There are many similarities between health issues affecting military and civilian patient populations, with the exception of the relatively small but vital segment of active soldiers who experience high-energy blast injuries during combat. A rising incidence of major injuries from explosive devices in recent campaigns has further complicated treatment and recovery, highlighting the need for tissue regenerative options and intensifying interest in the possible role of stem cells for military medicine. In this review we outline the array of tissue-specific injuries typically seen in modern combat - as well as address a few complications unique to soldiers--and discuss the state of current stem cell research in addressing each area. Embryonic, induced-pluripotent and adult stem cell sources are defined, along with advantages and disadvantages unique to each cell type. More detailed stem cell sources are described in the context of each tissue of interest, including neural, cardiopulmonary, musculoskeletal and sensory tissues, with brief discussion of their potential role in regenerative medicine moving forward. Additional commentary is given to military stem cell applications aside from regenerative medicine, such as blood pharming, immunomodulation and drug screening, with an overview of stem cell banking and the unique opportunity provided by the military and civilian overlap of stem cell research.

Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation.

PubMed

Leen, Ann M; Bollard, Catherine M; Mendizabal, Adam M; Shpall, Elizabeth J; Szabolcs, Paul; Antin, Joseph H; Kapoor, Neena; Pai, Sung-Yun; Rowley, Scott D; Kebriaei, Partow; Dey, Bimalangshu R; Grilley, Bambi J; Gee, Adrian P; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E

2013-06-27

Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2% -96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-related adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035.

Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells

PubMed Central

Shofuda, Tomoko; Kanematsu, Daisuke; Fukusumi, Hayato; Yamamoto, Atsuyo; Bamba, Yohei; Yoshitatsu, Sumiko; Suemizu, Hiroshi; Nakamura, Masato; Sugimoto, Yoshikazu; Furue, Miho Kusuda; Kohara, Arihiro; Akamatsu, Wado; Okada, Yohei; Okano, Hideyuki; Yamasaki, Mami; Kanemura, Yonehiro

2013-01-01

Placental tissue is a biomaterial with remarkable potential for use in regenerative medicine. It has a three-layer structure derived from the fetus (amnion and chorion) and the mother (decidua), and it contains huge numbers of cells. Moreover, placental tissue can be collected without any physical danger to the donor and can be matched with a variety of HLA types. The decidua-derived mesenchymal cells (DMCs) are highly proliferative fibroblast-like cells that express a similar pattern of CD antigens as bone marrow-derived mesenchymal cells (BM-MSCs). Here we demonstrated that induced pluripotent stem (iPS) cells could be efficiently generated from DMCs by retroviral transfer of reprogramming factor genes. DMC-hiPS cells showed equivalent characteristics to human embryonic stem cells (hESCs) in colony morphology, global gene expression profile (including human pluripotent stem cell markers), DNA methylation status of the OCT3/4 and NANOG promoters, and ability to differentiate into components of the three germ layers in vitro and in vivo. The RNA expression of XIST and the methylation status of its promoter region suggested that DMC-iPSCs, when maintained undifferentiated and pluripotent, had three distinct states: (1) complete X-chromosome reactivation, (2) one inactive X-chromosome, or (3) an epigenetic aberration. Because DMCs are derived from the maternal portion of the placenta, they can be collected with the full consent of the adult donor and have considerable ethical advantages for cell banking and the subsequent generation of human iPS cells for regenerative applications. PMID:26858858

Scalable human ES culture for therapeutic use: propagation, differentiation, genetic modification and regulatory issues.

PubMed

Rao, M

2008-01-01

Embryonic stem cells unlike most adult stem cell populations can replicate indefinitely while preserving genetic, epigenetic, mitochondrial and functional profiles. ESCs are therefore an excellent candidate cell type for providing a bank of cells for allogenic therapy and for introducing targeted genetic modifications for therapeutic intervention. This ability of prolonged self-renewal of stem cells and the unique advantages that this offers for gene therapy, discovery efforts, cell replacement, personalized medicine and other more direct applications requires the resolution of several important manufacturing, gene targeting and regulatory issues. In this review, we assess some of the advance made in developing scalable culture systems, improvement in vector design and gene insertion technology and the changing regulatory landscape.

Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation

PubMed Central

Leen, Ann M.; Bollard, Catherine M.; Mendizabal, Adam M.; Shpall, Elizabeth J.; Szabolcs, Paul; Antin, Joseph H.; Kapoor, Neena; Pai, Sung-Yun; Rowley, Scott D.; Kebriaei, Partow; Dey, Bimalangshu R.; Grilley, Bambi J.; Gee, Adrian P.; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.

2013-01-01

Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n = 50), 73.9% (95% CI, 51.2% -96.6%) for cytomegalovirus (n = 23), 77.8% for adenovirus (n = 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n = 9). Only 4 responders had a recurrence or progression. There were no immediate infusion-related adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035. PMID:23610374

76 FR 13572 - Proposed Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

.... Specifically, it addresses the following flooding sources: Left Bank Overflow Main Stem Skagit River, Left Bank Overflow Main Stem Skagit River/South Fork Skagit River, Left Bank Overflow North Fork Skagit River, Main Stem Skagit River, North Fork Skagit River, Overflow from the Main Stem Skagit River between the North...

Successful isolation of viable adipose-derived stem cells from human adipose tissue subject to long-term cryopreservation: positive implications for adult stem cell-based therapeutics in patients of advanced age.

PubMed

Devitt, Sean M; Carter, Cynthia M; Dierov, Raia; Weiss, Scott; Gersch, Robert P; Percec, Ivona

2015-01-01

We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved <1 year than from tissue cryopreserved >2 years, irrespective of patient age. However, this difference did not persist with continued growth and there were no significant differences in cell viability or growth at subsequent time points with respect to cryopreservation duration or patient age. Mesenchymal stem cell markers were maintained in all cohorts tested throughout the duration of the study. Consequently, longer cryopreservation negatively impacts initial live adipose-derived stem cell isolation; however, this effect is neutralized with continued cell growth. Patient age does not significantly impact stem cell isolation, viability, or growth. Cryopreservation of adipose tissue is an effective long-term banking method for isolation of adipose-derived stem cells in patients of varying ages.

Risk of Exposure to Zika Virus and Impact on Cord Blood Banking and Adult Unrelated Donors in Hematopoietic Cell Transplantation: The Canadian Blood Services Experience.

PubMed

Adams, Zachary; Morris, Gail; Campbell, Todd; Mostert, Karen; Dibdin, Nicholas; Fearon, Margaret; Elmoazzen, Heidi; Mercer, Dena; Young, Kimberly; Allan, David

2018-04-01

Zika virus has emerged as a potential threat to the Canadian blood supply system. Stem cell donors within Canadian Blood Services' Cord Blood Bank (CBB) and OneMatch Stem Cell and Marrow Network (OM) now undergo screening measures designed to reduce the risk of Zika virus transmission. The impact these screening measures have on cord blood and unrelated adult stem cell donations is currently unknown. Among 146 donor workups initiated by OM between July 2016 and May 2017, 102 were completed and 44 workups were canceled. There were 17 potential donors (11.6%) with a risk of Zika virus exposure identified by the donor questionnaire (13 completed, 4 canceled workups). None of the workups involved a donor diagnosed with confirmed Zika virus within the past 6 months. Only 1 of the 44 canceled workups (and only 1 of 4 cases with a risk of Zika transmission) was canceled because of the risk of Zika transmission, and a backup donor was selected. Canadian Blood Services' CBB identified 25 of 875 cord blood units (2.9%) from women who donated their infants' cord blood and underwent screening that otherwise met the initial cell number thresholds for banking and had at least 1 risk factor for exposure to Zika virus. No women were diagnosed with Zika virus at any point of their pregnancy. All 25 units were discarded. Unrelated donors at OM have a higher incidence of a risk of exposure to Zika virus compared with cord blood donors. Only rarely did transplant centers cancel donor workups due to potential Zika virus exposure. The impact of screening for Zika virus exposure risk on cord blood banking was minor. Continued vigilance and surveillance is recommended. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Fostering public cord blood banking and research in Canada.

PubMed

Isasi, Rosario; Dalpe, Gratien; Knoppers, Bartha M

2013-12-01

In June 2013, Canadian Blood Services (CBS) established the National Public Cord Blood Bank (NPCBB) accessible to Canadian and international patients and researchers. The NPCBB promotes efforts that contribute to research and improved clinical care by making units not suitable for banking or transplantation available for research. In the context of the NPCBB of the CBS, this article will focus on the practical tools (e.g., consent protocols) developed to optimize umbilical cord blood (UCB) banking and research while enabling ethical provenance of UCB stem cells. The Canadian approach represents an ideal model for comparison as it is a country in which the national public bank (and other regional/provincial public banks) coexists with private companies.

Application of adipocyte-derived stem cells in treatment of cutaneous radiation syndrome.

PubMed

Riccobono, Diane; Agay, Diane; Scherthan, Harry; Forcheron, Fabien; Vivier, Mylène; Ballester, Bruno; Meineke, Viktor; Drouet, Michel

2012-08-01

Cutaneous radiation syndrome caused by local high dose irradiation is characterized by delayed outcome and incomplete healing. Recent therapeutic management of accidentally irradiated burn patients has suggested the benefit of local cellular therapy using mesenchymal stem cell grafting. According to the proposed strategy of early treatment, large amounts of stem cells would be necessary in the days following exposure and hospitalization, which would require allogeneic stem cells banking. In this context, the authors compared the benefit of local autologous and allogeneic adipocyte-derived stem cell injection in a large animal model. Minipigs were locally irradiated using a 60Co gamma source at a dose of 50 Gy and divided into three groups. Two groups were grafted with autologous (n = 5) or allogeneic (n = 5) adipocyte-derived stem cells four times after the radiation exposure, whereas the control group received the vehicle without cells (n = 8). A clinical score was elaborated to compare the efficiency of the three treatments. All controls exhibited local inflammatory injuries leading to a persistent painful necrosis, thus mimicking the clinical evolution in human victims. In the autologous adipocyte-derived stem cells group, skin healing without necrosis or uncontrollable pain was observed. In contrast, the clinical outcome was not significantly different in the adipocyte-derived stem cell allogeneic group when compared with controls. This study suggests that autologous adipocyte-derived stem cell grafting improves cutaneous radiation syndrome wound healing, whereas allogeneic adipocyte derived stem cells do not. Further studies will establish whether manipulation of allogeneic stem cells will improve their therapeutic potential.

Hematology Glossary

MedlinePlus

... of ASH educational meetings and webinars ASH Image Bank Educational Web-based library of hematologic imagery ... quickly allogeneic: refers to blood, stem cells, bone marrow, or other tissue that is transferred from one person to another ...

HLA Engineering of Human Pluripotent Stem Cells

PubMed Central

Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-01-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

HLA engineering of human pluripotent stem cells.

PubMed

Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-06-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

An overview on ethical considerations in stem cell research in Iran and ethical recommendations: A review.

PubMed

Farajkhoda, Tahmineh

2017-02-01

Conducting research on the stem cell lines might bring some worthy good to public. Human Stem Cells (hSCs) research has provided opportunities for scientific progresses and new therapies, but some complex ethical matters should be noticed to ensure that stem cell research is carried out in an ethically appropriate manner. The aim of this review article is to discuss the importance of stem cell research, code of ethics for stem cell research in Iran and ethical recommendation. Generation of stem cells for research from human embryo or adult stem cells, saving, maintenance and using of them are the main ethical, legal and jurisprudence concerns in Iran. Concerns regarding human reproduction or human cloning, breach of human dignity, genetic manipulation and probability of tumorogenisity are observed in adult/somatic stem cells. Destruction of embryo to generate stem cell is an important matter in Iran. In this regards, obtaining stem cell from donated frozen embryos through infertility treatment that would be discarded is an acceptable solution in Iran for generation of embryo for research. Ethical, legal, and jurisprudence strategies for using adult/somatic stem cells are determination of ownership of stem cells, trade prohibition of human body, supervision on bio banks and information of Oversight Committee on Stem Cell Research. Recommendations to handle ethical issues for conducting stem cell research are well-designed studies, compliance codes of ethics in biomedical research (specifically codes of ethics on stem cell research, codes of ethics on clinical trials studies and codes of ethics on animals studies), appropriate collaboration with ethics committees and respecting of rights of participants (including both of human and animal rights) in research. In addition, there is a necessity for extending global networks of bioethics for strengthening communications within organizations at both the regional and international level, strengthening legislation systems, designing and establishing convenient collaborative educational courses at different levels.

An overview on ethical considerations in stem cell research in Iran and ethical recommendations: A review

PubMed Central

Farajkhoda, Tahmineh

2017-01-01

Conducting research on the stem cell lines might bring some worthy good to public. Human Stem Cells (hSCs) research has provided opportunities for scientific progresses and new therapies, but some complex ethical matters should be noticed to ensure that stem cell research is carried out in an ethically appropriate manner. The aim of this review article is to discuss the importance of stem cell research, code of ethics for stem cell research in Iran and ethical recommendation. Generation of stem cells for research from human embryo or adult stem cells, saving, maintenance and using of them are the main ethical, legal and jurisprudence concerns in Iran. Concerns regarding human reproduction or human cloning, breach of human dignity, genetic manipulation and probability of tumorogenisity are observed in adult/somatic stem cells. Destruction of embryo to generate stem cell is an important matter in Iran. In this regards, obtaining stem cell from donated frozen embryos through infertility treatment that would be discarded is an acceptable solution in Iran for generation of embryo for research. Ethical, legal, and jurisprudence strategies for using adult/somatic stem cells are determination of ownership of stem cells, trade prohibition of human body, supervision on bio banks and information of Oversight Committee on Stem Cell Research. Recommendations to handle ethical issues for conducting stem cell research are well-designed studies, compliance codes of ethics in biomedical research (specifically codes of ethics on stem cell research, codes of ethics on clinical trials studies and codes of ethics on animals studies), appropriate collaboration with ethics committees and respecting of rights of participants (including both of human and animal rights) in research. In addition, there is a necessity for extending global networks of bioethics for strengthening communications within organizations at both the regional and international level, strengthening legislation systems, designing and establishing convenient collaborative educational courses at different levels. PMID:28462397

Allogenic banking of dental pulp stem cells for innovative therapeutics.

PubMed

Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

2015-08-26

Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

Allogenic banking of dental pulp stem cells for innovative therapeutics

PubMed Central

Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

2015-01-01

Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat. PMID:26328017

The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine.

PubMed

Hedges, Erin C; Mehler, Vera J; Nishimura, Agnes L

2016-01-01

In recent years several genes have linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular pathways. Thus, as never before, compounds with potential applications for regenerative medicine can be specifically tailored in patient derived cultures. In this review, we discuss how patient specific induced pluripotent stem cells (iPSCs) have been used to model ALS and FTD and the most recent drug screening targets for these diseases. We also discuss how an iPSC bank would improve the quality of the available cell lines and how it would increase knowledge about the ALS/FTD disease spectrum.

A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem Cells.

PubMed

Kurtz, Andreas; Seltmann, Stefanie; Bairoch, Amos; Bittner, Marie-Sophie; Bruce, Kevin; Capes-Davis, Amanda; Clarke, Laura; Crook, Jeremy M; Daheron, Laurence; Dewender, Johannes; Faulconbridge, Adam; Fujibuchi, Wataru; Gutteridge, Alexander; Hei, Derek J; Kim, Yong-Ou; Kim, Jung-Hyun; Kokocinski, Anja Kolb-; Lekschas, Fritz; Lomax, Geoffrey P; Loring, Jeanne F; Ludwig, Tenneille; Mah, Nancy; Matsui, Tohru; Müller, Robert; Parkinson, Helen; Sheldon, Michael; Smith, Kelly; Stachelscheid, Harald; Stacey, Glyn; Streeter, Ian; Veiga, Anna; Xu, Ren-He

2018-01-09

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Preparation, characterization, and banking of clinical-grade cells for neural transplantation: Scale up, fingerprinting, and genomic stability of stem cell lines.

PubMed

Natalwala, Ammar; Kunath, Tilo

2017-01-01

Parkinson's disease is a complex and progressive neurodegenerative condition that is characterized by the severe loss of midbrain dopaminergic (mDA) neurons, which innervate the striatum. Cell transplantation therapies to rebuild this dopaminergic network have been attempted for over 30 years. The most promising outcomes were observed when human fetal mesencephalic tissue was used as the source of cells for transplantation. However, reliance on terminations for a Parkinson's therapy presents significant logistical and ethical hurdles. An alternative source of transplantable mDA neurons is urgently needed, and the solution may come from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). Protocols to differentiate hESCs/iPSCs toward mDA neurons are now robust and efficient, and upon grafting the cells rescue preclinical animal models of Parkinson's disease. The challenge now is to apply Good Manufacturing Practice (GMP) to the academic discoveries and protocols to produce clinical-grade transplantable mDA cells. Major technical and logistical considerations include (i) source of hESC or iPSC line, (ii) GMP compliance of the differentiation protocol and all reagents, (iii) characterization of the cell product in terms of identity, safety, and efficacy, (iv) characterization of genomic state and stability, and (v) banking of a transplantation-ready cell product. Approaches and solutions to these challenges are reviewed here. © 2017 Elsevier B.V. All rights reserved.

Cord Blood Banking for Potential Future Transplantation.

PubMed

Shearer, William T; Lubin, Bertram H; Cairo, Mitchell S; Notarangelo, Luigi D

2017-11-01

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that operate or have a relationship with cord blood banking programs. The information on all aspects of cord blood banking gathered in this policy statement will facilitate parental choice for public or private cord blood banking. Copyright © 2017 by the American Academy of Pediatrics.

Social science in a stem cell laboratory: what happened when social and life sciences met.

PubMed

Stacey, Glyn; Stephens, Neil

2012-01-01

We describe the experience of conducting intensive social science research at the UK Stem Cell Bank from the viewpoint of both the person conducting the social science research and the Director of the Bank. We detail the initial misunderstandings and concerns held by both and the problems these caused. Then we describe how the relationship developed as the project progressed and shared benefits became apparent. Finally, while acknowledging potential areas of tension between the life and social sciences, we suggest further interaction between the disciplines would prove beneficial for both and speculate as to how this may be achieved. In the discussion we identify a set of learning points from our experience and definitions of social science terminology that may help to inform future engagements between life and social scientists.

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks

PubMed Central

Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T.; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

2017-01-01

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23–230) and 8.6×108 (range 0.7–75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. PMID:28302713

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.

PubMed

Rafii, Hanadi; Bernaudin, Françoise; Rouard, Helene; Vanneaux, Valérie; Ruggeri, Annalisa; Cavazzana, Marina; Gauthereau, Valerie; Stanislas, Aurélie; Benkerrou, Malika; De Montalembert, Mariane; Ferry, Christele; Girot, Robert; Arnaud, Cecile; Kamdem, Annie; Gour, Joelle; Touboul, Claudine; Cras, Audrey; Kuentz, Mathieu; Rieux, Claire; Volt, Fernanda; Cappelli, Barbara; Maio, Karina T; Paviglianiti, Annalisa; Kenzey, Chantal; Larghero, Jerome; Gluckman, Eliane

2017-06-01

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23-230) and 8.6×10 8 (range 0.7-75×10 8 ), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units. Copyright© Ferrata Storti Foundation.

A new method for cryopreserving adipose-derived stem cells: an attractive and suitable large-scale and long-term cell banking technology.

PubMed

De Rosa, Alfredo; De Francesco, Francesco; Tirino, Virginia; Ferraro, Giuseppe A; Desiderio, Vincenzo; Paino, Francesca; Pirozzi, Giuseppe; D'Andrea, Francesco; Papaccio, Gianpaolo

2009-12-01

Recent studies have shown potential ways for improving stem cell cryopreservation. The major need for autologous stem cell use is a long-term storage: this arises from the humans' hope of future use of their own cells. Therefore, it is important to evaluate the cell potential of vitality and differentiation before and after cryopreservation. Although several studies have shown a long-term preservation of adipose tissue, a few of them focused their attention to stem cells. The aim of this study was to evaluate the fate of cryopreserved stem cells collected from adipose tissue and stored at low a temperature in liquid nitrogen through an optimal cryopreservation solution (using slowly cooling in 6% threalose, 4% dimethyl sulfoxide, and 10% fetal bovine serum) and to develop a novel approach to efficiently preserve adipose-derived stem cells (ASCs) for future clinical applications. Results showed that stem cells, after being thawed, are still capable of differentiation and express all surface antigens detected before storage, confirming the integrity of their biology. In particular, ASCs differentiated into adipocytes, showed diffuse positivity for PPARgamma and adiponectin, and were also able to differentiate into endothelial cells without addition of angiogenic factors. Therefore, ASCs can be long-term cryopreserved, and this, due to their great numbers, is an attractive tool for clinical applications as well as of impact for the derived market.

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

PubMed Central

2014-01-01

Introduction Regenerative medicine challenges researchers to find noncontroversial, safe and abundant stem cell sources. In this context, harvesting from asystolic donors could represent an innovative and unlimited reservoir of different stem cells. In this study, cadaveric vascular tissues were established as an alternative source of human cadaver mesenchymal stromal/stem cells (hC-MSCs). We reported the successful cell isolation from postmortem arterial segments stored in a tissue-banking facility for at least 5 years. Methods After thawing, hC-MSCs were isolated with a high efficiency (12 × 106) and characterized with flow cytometry, immunofluorescence, molecular and ultrastructural approaches. Results In early passages, hC-MSCs were clonogenic, highly proliferative and expressed mesenchymal (CD44, CD73, CD90, CD105, HLA-G), stemness (Stro-1, Oct-4, Notch-1), pericyte (CD146, PDGFR-β, NG2) and neuronal (Nestin) markers; hematopoietic and vascular markers were negative. These cells had colony and spheroid-forming abilities, multipotency for their potential to differentiate in multiple mesengenic lineages and immunosuppressive activity to counteract proliferation of phytohemagglutinin-stimulated blood mononuclear cells. Conclusions The efficient procurement of stem cells from cadaveric sources, as postmortem vascular tissues, demonstrates that such cells can survive to prolonged ischemic insult, anoxia, freezing and dehydration injuries, thus paving the way for a scientific revolution where cadaver stromal/stem cells could effectively treat patients demanding cell therapies. PMID:24429026

Public Awareness on Cord Blood Banking in Saudi Arabia

PubMed Central

AlTwijri, Sulaiman; AlSemari, Hadeel; Saade, Mayssa; Alaskar, Ahmed

2018-01-01

Background In the last decade, cord blood (CB) has proven to be a valuable source of hematopoietic stem cells for transplantation to treat many hematological disorders. Since then, many CB banks have been established worldwide. Our aim was to estimate the level of public awareness of CB banking in Saudi Arabia. Study Design and Methods A self-administered questionnaire of 22 multiple choices was conveniently distributed, consisting of demographics, awareness measure, attitude toward banking preference, and donation for research data. Results A total of 1146 participants have completed the questionnaire. The majority were young female 19–25 years old (26%), who are college graduates (57%) with middle class socioeconomic status (82%). The subjective assessment of the overall knowledge was inadequate (66%). For the objective assessment, 12 questions were asked about CB source, collection, storage, and usage. Only half of the subjects (52%) knew that CB is a source of stem cells. More than half did not know the main use of CB. About half did not know about the method of collection nor the condition of storing. Conclusion This study shows a high lack of knowledge about CB banking. More than half of the subjects were unaware of CB banking and its uses. However, most subjects are accepting CB storage, which anticipates great impact and efficacy on educational programs. Moreover, the data demonstrated that health professionals were not the source of knowledge. We recommend having comprehensive educational campaigns with clear information about CB banking to facilitate positive perspectives towards donation and scientific research. PMID:29765424

The implementation of tissue banking experiences for setting up a cGMP cell manufacturing facility.

PubMed

Arjmand, Babak; Emami-Razavi, Seyed Hassan; Larijani, Bagher; Norouzi-Javidan, Abbas; Aghayan, Hamid Reza

2012-12-01

Cell manufacturing for clinical applications is a unique form of biologics manufacturing that relies on maintenance of stringent work practices designed to ensure product consistency and prevent contamination by microorganisms or by another patient's cells. More extensive, prolonged laboratory processes involve greater risk of complications and possibly adverse events for the recipient, and so the need for control is correspondingly greater. To minimize the associate risks of cell manufacturing adhering to international quality standards is critical. Current good tissue practice (cGTP) and current good manufacturing practice (cGMP) are examples of general standards that draw a baseline for cell manufacturing facilities. In recent years, stem cell researches have found great public interest in Iran and different cell therapy projects have been started in country. In this review we described the role of our tissue banking experiences in establishing a new cGMP cell manufacturing facility. The authors concluded that, tissue banks and tissue banking experts can broaden their roles from preparing tissue grafts to manufacturing cell and tissue engineered products for translational researches and phase I clinical trials. Also they can collaborate with cell processing laboratories to develop SOPs, implement quality management system, and design cGMP facilities.

Umbilical Cord Blood: Counselling, Collection, and Banking.

PubMed

Armson, B Anthony; Allan, David S; Casper, Robert F

2015-09-01

To review current evidence regarding umbilical cord blood counselling, collection, and banking and to provide guidelines for Canadian health care professionals regarding patient education, informed consent, procedural aspects, and options for cord blood banking in Canada. Selective or routine collection and banking of umbilical cord blood for future stem cell transplantation for autologous (self) or allogeneic (related or unrelated) treatment of malignant and non-malignant disorders in children and adults. Cord blood can be collected using in utero or ex utero techniques. Umbilical cord blood counselling, collection, and banking, education of health care professionals, indications for cord blood collection, short- and long-term risk and benefits, maternal and perinatal morbidity, parental satisfaction, and health care costs. Published literature was retrieved through searches of Medline and PubMed beginning in September 2013 using appropriate controlled MeSH vocabulary (fetal blood, pregnancy, transplantation, ethics) and key words (umbilical cord blood, banking, collection, pregnancy, transplantation, ethics, public, private). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to September 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Umbilical cord blood is a readily available source of hematopoetic stem cells used with increasing frequency as an alternative to bone marrow or peripheral stem cell transplantation to treat malignant and non-malignant conditions in children and adults. There is minimal harm to the mother or newborn provided that priority is given to maternal/newborn safety during childbirth management. Recipients of umbilical cord stem cells may experience graft-versus-host disease, transfer of infection or genetic abnormalities, or therapeutic failure. The financial burden on the health system for public cord blood banking and on families for private cord blood banking is considerable. Recommendations 1. Health care professionals should be well-informed about cord blood collection and storage and about factors that influence the volume, quality, and ability to collect a cord blood unit. (III-A) 2. Health care professionals caring for women and families who choose private umbilical cord blood banking must disclose any financial interests or potential conflicts of interest. (III-A) 3. Pregnant women should be provided with unbiased information about umbilical cord blood banking options, including the benefits and limitations of public and private banks. (III-A) 4. Health care professionals should obtain consent from mothers for the collection of umbilical cord blood prior to the onset of active labour, ideally during the third trimester, with ample time to address any questions. (III-A) 5. Health care professionals must be trained in standardized procedures (ex utero and in utero techniques) for cord blood collection to ensure the sterility and quality of the collected unit. (II-2A) 6. Umbilical cord blood should be collected with the goal of maximizing the content of hematopoietic progenitors through the volume collected. The decision to bank the unit will depend upon specific measures of graft potency. (II-2A) 7. Umbilical cord blood collection must not adversely affect the health of the mother or newborn. Cord blood collection should not interfere with delayed cord clamping. (III-E) 8. Health care professionals should inform pregnant women and their partners of the benefits of delayed cord clamping and of its impact on cord blood collection and banking. (II-2A) 9. Cord blood units collected for public or private banking can be used for biomedical research, provided consent is obtained, when units cannot be banked or when consent for banking is withdrawn. (II-3B) 10. Mothers may be approached to donate cells for biomedical research. Informed consent for research using cord blood should ideally be obtained prior to the onset of active labour or elective Caesarean section following established research ethics guidelines. (II-2A).

Pilot social feasibility study for the establishment of a public human umbilical cord blood stem cell bank in South Africa.

PubMed

Meissner-Roloff, Madelein; Young, Wendy; Rangaka, Isabella; Lombaard, Hennie; Dhai, Ames; Tsotsi, Norma; Pepper, Michael S

2012-12-01

There is a large unmet need in South Africa for bone marrow transplantation. Umbilical cord blood (UCB) is an important source of stem cells for the treatment of haematological and non-haematological diseases. Access to the two existing private umbilical cord blood stem cell banks (UCB SCBs) in South Africa is limited to individuals that can afford it, which further aggravates the ever increasing divide between families from different socio-economic classes. The problem is compounded by a severe global shortage of genetically compatible samples, representative of the South African demographics. Establishing a public human UCB SCB in South Africa would provide more South Africans with access to previously unavailable treatment in the form of affordable, genetically compatible stem cells for bone marrow transplantation. A public UCB SCB has many facets to consider, one of which is public preparedness and support for the bank. This was assessed in a social feasibility pilot study which is reported here. In addition to the findings of this social feasibility study, other important considerations for establishing a public human UCB SCB in SA include; (a) testing the samples for HIV and other infectious diseases (required for compliance with international regulatory standards); (b) flow cytometric analysis for enumeration of CD34+ UCB stem cells; (c) mapping of HLA genotypes/alleles; and (d) a study of the economic feasibility of this endeavour.The social feasibility study was conducted to gauge public preparedness and support for a public SCB through patient interviews and questionnaires. The process was dynamic due to its novel nature for interviewers and interviewees alike. Many obstacles were met and dealt with which lead to the compilation of results discussed here in the form of a pilot social feasibility study.In the South African context, we are faced with unique and rich challenges relating to cultural and religious differences that are further augmented by linguistic constraints, educational insufficiencies and logistical and administrative limitations. Complicating factors encountered during the informed consent process included cultural differences, religious practices, traditions and superstitions together with language constraints and an educational disparity.Despite many initial obstacles, preliminary results from the informed consent questionnaire were favourable with regard to the establishment of a public UCB SCB. These initial results prompted the revision of the questionnaire and interview process and the compilation of a more succinct and coherent definitive social feasibility study which will form a separate study and which we hope will ultimately assist in the decision of whether or not to establish a public UCB SCB in South Africa. Nevertheless, results from this pilot study appear to be favourable and highlight particular areas which could influence community support for a public SCB. Educating the general public with regard to the workings and benefits of public stem cell banking is the first step in determining the viability of such an undertaking-a unique and rich challenge in the South African context.

Human embryonic stem cell therapies for neurodegenerative diseases.

PubMed

Tomaskovic-Crook, Eva; Crook, Jeremy M

2011-06-01

There is a renewed enthusiasm for the clinical translation of human embryonic stem (hES) cells. This is abetted by putative clinically-compliant strategies for hES cell maintenance and directed differentiation, greater understanding of and accessibility to cells through formal cell registries and centralized cell banking for distribution, the revised US government policy on funding hES cell research, and paradoxically the discovery of induced pluripotent stem (iPS) cells. Additionally, as we consider the constraints (practical and fiscal) of delivering cell therapies for global healthcare, the more efficient and economical application of allogeneic vs autologous treatments will bolster the clinical entry of hES cell derivatives. Neurodegenerative disorders such as Parkinson's disease are primary candidates for hES cell therapy, although there are significant hurdles to be overcome. The present review considers key advances and challenges to translating hES cells into novel therapies for neurodegenerative diseases, with special consideration given to Parkinson's disease and Alzheimer's disease. Importantly, despite the focus on degenerative brain disorders and hES cells, many of the issues canvassed by this review are relevant to systemic application of hES cells and other pluripotent stem cells such as iPS cells.

Imperative role of dental pulp stem cells in regenerative therapies: a systematic review.

PubMed

Kabir, Ramchandra; Gupta, Manish; Aggarwal, Avanti; Sharma, Deepak; Sarin, Anurag; Kola, Mohammed Zaheer

2014-01-01

Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like "dental pulp stem cells", "regeneration", "medical applications", "tissue engineering". DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective.

Biobanking in a Constantly Developing Medical World

PubMed Central

Ciurea, Marius Eugen; Purcaru, Stefana Oana; Tache, Daniela Elise; Tataranu, Ligia Gabriela; Lupu, Mihaela; Dricu, Anica

2013-01-01

Biobank is a very sophisticated system that consists of a programmed storage of biological material and corresponding data. Biobanks are created to be used in medical research, in clinical and translational medicine, and in healthcare. In the past 20 years, a large number of biobanks have been set up around the world, to support the modern research directions in medicine such as omix and personalized medicine. More recently, embryonic and adult stem cell banks have been developed. Stem cell banking was reported to be required for medical research as well as clinical transplant applications. The quality of the samples stored in a biobank is very important. The standardization is also important; the biological material stored in a biobank must be processed in a manner that allows compatibility with other biobanks that preserve samples in the same field. In this paper, we review some issues related to biobanks purposes, quality, harmonization, and their financial and ethical aspects. PMID:24174912

Imperative Role of Dental Pulp Stem Cells in Regenerative Therapies: A Systematic Review

PubMed Central

Kabir, Ramchandra; Gupta, Manish; Aggarwal, Avanti; Sharma, Deepak; Sarin, Anurag; Kola, Mohammed Zaheer

2014-01-01

Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like “dental pulp stem cells”, “regeneration”, “medical applications”, “tissue engineering”. DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective. PMID:24665194

Establishment of a Brazilian line of human embryonic stem cells in defined medium: implications for cell therapy in an ethnically diverse population.

PubMed

Fraga, Ana M; Sukoyan, Marina; Rajan, Prithi; Braga, Daniela Paes de Almeida Ferreira; Iaconelli, Assumpto; Franco, José Gonçalves; Borges, Edson; Pereira, Lygia V

2011-01-01

Pluripotent human embryonic stem (hES) cells are an important experimental tool for basic and applied research, and a potential source of different tissues for transplantation. However, one important challenge for the clinical use of these cells is the issue of immunocompatibility, which may be dealt with by the establishment of hES cell banks to attend different populations. Here we describe the derivation and characterization of a line of hES cells from the Brazilian population, named BR-1, in commercial defined medium. In contrast to the other hES cell lines established in defined medium, BR-1 maintained a stable normal karyotype as determined by genomic array analysis after 6 months in continuous culture (passage 29). To our knowledge, this is the first reported line of hES cells derived in South America. We have determined its genomic ancestry and compared the HLA-profile of BR-1 and another 22 hES cell lines established elsewhere with those of the Brazilian population, finding they would match only 0.011% of those individuals. Our results highlight the challenges involved in hES cell banking for populations with a high degree of ethnic admixture.

Evaluation of a xeno-free protocol for long-term cryopreservation of cord blood cells.

PubMed

Mairhofer, M; Schulz, J C; Parth, M; Beer, U; Zimmermann, H; Kolbus, A

2013-01-01

Cord blood is regarded as a powerful source for adult stem cells. Cord blood transplants have been used successfully to treat children and adults in autologous and allogeneic settings. Nevertheless, in many cases, the clinically relevant cell number (CD34+ cells and total leukocytes) is a limiting factor. To enable standardized cell banking and future in vitro expansion of adult stem/progenitor cells, elimination of serum, which inevitably differs from lot to lot and donor to donor, is highly desirable. Here, we demonstrate the feasibility of a xeno-free, chemically defined cryopreservation procedure for cord blood-derived cells over a period of 1 year. Cell recoveries with respect to retrieval of clinically relevant CD34+ cells, colony-forming units, and in vitro cultures of erythroid progenitor cells under standardized conditions were analyzed after 1 week or 1 year of cryopreservation and found to be very high and similar to the samples before freezing. The established xeno-free procedure is an important step toward using the full potential of adult stem cells from cord blood, enabling the elimination of serum-derived factors negatively influencing proliferation, differentiation, and survival of hematopoietic stem cells.

Stem Cells for Osteochondral Regeneration.

PubMed

Canadas, Raphaël F; Pirraco, Rogério P; Oliveira, J Miguel; Reis, Rui L; Marques, Alexandra P

2018-01-01

Stem cell research plays a central role in the future of medicine, which is mainly dependent on the advances on regenerative medicine (RM), specifically in the disciplines of tissue engineering (TE) and cellular therapeutics. All RM strategies depend upon the harnessing, stimulation, or guidance of endogenous developmental or repair processes in which cells have an important role. Among the most clinically challenging disorders, cartilage degeneration, which also affects subchondral bone becoming an osteochondral (OC) defect, is one of the most demanding. Although primary cells have been clinically applied, stem cells are currently seen as the promising tool of RM-related research because of its availability, in vitro proliferation ability, pluri- or multipotency, and immunosuppressive features. Being the OC unit, a transition from the bone to cartilage, mesenchymal stem cells (MSCs) are the main focus for OC regeneration. Promising alternatives, which can also be obtained from the patient or at banks and have great differentiation potential toward a wide range of specific cell types, have been reported. Still, ethical concerns and tumorigenic risk are currently under discussion and assessment. In this book chapter, we revise the existing stem cell-based approaches for engineering bone and cartilage, focusing on cell therapy and TE. Furthermore, 3D OC composites based on cell co-cultures are described. Finally, future directions and challenges still to be faced are critically discussed.

Regenerative medicine using dental pulp stem cells for liver diseases.

PubMed

Ohkoshi, Shogo; Hara, Hajime; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko

2017-02-06

Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.

Developing Induced Pluripotent Stem Cell-Based Therapy for the Masses.

PubMed

Rao, Mahendra S; Atala, Anthony

2016-02-01

The discovery of induced pluripotent stem cells and the ability to manufacture them using clinically compliant protocols has the potential to revolutionize the field of regenerative medicine. However, realizing this potential requires the development of processes that are reliable, reproducible, and cost-effective and that at the same time do not compromise the safety of the individuals receiving this therapy. In the present report, we discuss how cost reductions can be obtained using our experience with obtaining approval of biologic agents, autologous therapy, and the recent approval of cord blood banks. Significance: For therapy to be widely available, the cost of manufacturing stem cells must be reduced. The steps proposed in the present report, when implemented, have the potential to reduce these costs significantly. ©AlphaMed Press.

Human mesenchymal stem cells - current trends and future prospective

PubMed Central

Ullah, Imran; Subbarao, Raghavendra Baregundi; Rho, Gyu Jin

2015-01-01

Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials. PMID:25797907

Cord blood units collected at a remote site: a collaborative endeavor to collect umbilical cord blood through the Hawaii Cord Blood Bank and store the units at the Puget Sound Blood Center.

PubMed

Wada, Randal K; Bradford, Andrea; Moogk, Margery; Yim, Robyn; Strong, D Michael; Drachman, Jonathan; Reems, Jo Anna

2004-01-01

Umbilical cord blood is a useful source of hematopoietic stem cells, especially because compared to equivalent HLA-matched stem cells from unrelated adult donors. A network of community collection sites targeted at particular ethnic groups and serviced by a central processing and storage facility can maximize the genetic diversity of banked cord blood units (CBUs) in a cost-effective fashion. The present study compared CBUs collected near the Puget Sound Blood Center in Seattle, WA, with those collected in Honolulu, HI, and processed in Seattle. Evaluated variables include collection volume, total nucleated cell count, cellular viability, CD34+ cell count, clonogenic activity, and donor race for a total of 1646 CBUs received from July 1998 through November 2002. CBUs from the two sites did not differ with regard to volume or total nucleated cells. Those from Hawaii had significantly longer transit times (p < 0.001) and lower whole cord blood cell viability. However, the numbers of CFU and viable CD34+ cells were not affected by remote collection. CBUs screened from Seattle were largely from Caucasian donors, whereas over 85 percent of those from Honolulu were from donors of Asian-Pacific Islander or mixed ethnicity. These studies demonstrate the feasibility of long-distance umbilical cord blood banking. Arrangements such as those described here could be used to help target cost-effective collection from minority populations and increase the HLA and ethnic diversity for CBUs.

A Simple and Efficient Method of Slow Freezing for Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.

PubMed

Imaizumi, Keitaro; Iha, Momoe; Nishishita, Naoki; Kawamata, Shin; Nishikawa, Shinichi; Akuta, Teruo

2016-01-01

Protocols available for the cryopreservation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells are very inefficient and laborious compared to those for the cryopreservation of murine ES/iPS cells or other general cell lines. While the vitrification method may be adequate when working with small numbers of human ES/iPS cells, it requires special skills and is unsuitable when working with large cell numbers. Here, we describe a simple and efficient method for the cryopreservation of hES/hiPS cells that is based on a conventional slow freezing method that uses a combination of Pronase/EDTA for Stem™ and CP-5E™ [final concentrations: 6 % hydroxyethyl starch, 5 % DMSO, and 5 % ethylene glycol in saline]. CP-5E™ is highly effective for the cryopreservation of small cell clumps produced by hES/hiPS colony detachment in the presence of Pronase and EDTA (Pronase/EDTA for Stem™, a formulation containing multiple digestive enzymes from Streptomyces griseus). This novel method would be quite useful for large-scale hES/iPS cell banking for use in clinical applications.

Ensuring the Quality of Stem Cell-Derived In Vitro Models for Toxicity Testing.

PubMed

Stacey, Glyn N; Coecke, Sandra; Price, Anna-Bal; Healy, Lyn; Jennings, Paul; Wilmes, Anja; Pinset, Christian; Ingelman-Sundberg, Magnus; Louisse, Jochem; Haupt, Simone; Kidd, Darren; Robitski, Andrea; Jahnke, Heinz-Georg; Lemaitre, Gilles; Myatt, Glenn

Quality control of cell cultures used in new in vitro toxicology assays is crucial to the provision of reliable, reproducible and accurate toxicity data on new drugs or constituents of new consumer products. This chapter explores the key scientific and ethical criteria that must be addressed at the earliest stages of developing toxicology assays based on human pluripotent stem cell (hPSC) lines. It also identifies key considerations for such assays to be acceptable for regulatory, laboratory safety and commercial purposes. Also addressed is the development of hPSC-based assays for the tissue and cell types of greatest interest in drug toxicology. The chapter draws on a range of expert opinion within the European Commission/Cosmetics Europe-funded alternative testing cluster SEURAT-1 and consensus from international groups delivering this guidance such as the International Stem Cell Banking Initiative. Accordingly, the chapter summarizes the most up-date best practices in the use and quality control of human Pluripotent Stem Cell lines in the development of in vitro toxicity assays from leading experts in the field.

Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified?

PubMed Central

Fisk, Nicholas M; Roberts, Irene A. G; Markwald, Roger; Mironov, Vladimir

2005-01-01

Background to the debate: Umbilical cord blood—the blood that remains in the placenta after birth—can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation.) PMID:15737000

Can routine commercial cord blood banking be scientifically and ethically justified?

PubMed

Fisk, Nicholas M; Roberts, Irene A G; Markwald, Roger; Mironov, Vladimir

2005-02-01

Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation).

Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa

PubMed Central

Sebastiano, Vittorio; Zhen, Hanson Hui; Haddad, Bahareh; Bashkirova, Elizaveta; Melo, Sandra P.; Wang, Pei; Leung, Thomas L.; Siprashvili, Zurab; Tichy, Andrea; Li, Jiang; Ameen, Mohammed; Hawkins, John; Lee, Susie; Li, Lingjie; Schwertschkow, Aaron; Bauer, Gerhard; Lisowski, Leszek; Kay, Mark A.; Kim, Seung K.; Lane, Alfred T.; Wernig, Marius; Oro, Anthony E.

2015-01-01

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB. PMID:25429056

Ethnicity, equity and public benefit: a critical evaluation of public umbilical cord blood banking in Australia.

PubMed

Samuel, G N; Kerridge, I H; Vowels, M; Trickett, A; Chapman, J; Dobbins, T

2007-10-01

Over the past decade umbilical cord blood (UCB) has been increasingly used as a source of haematopoietic stem cells (HSCs) for patients who require a HSC transplant but do not have an HLA-matched donor. It was anticipated that using UCB as an alternative source of HSCs would increase the chance of finding a donor, particularly for the otherwise underrepresented ethnic minority groups. To evaluate the effectiveness of the Australian public UCB banks to increase the ethnic diversity of available HSC donations, this paper analyses the ethnic diversity of the Sydney Cord Blood Bank (SCBB), comparing this diversity to that of the Australian Bone Marrow Donor Registry (ABMDR). It also examines the ethnic diversity of those patients who, after requesting a haematopoietic stem cell transplantation in the 2-year period between 2003 and 2005, managed to find a suitably matched bone marrow or UCB donor. We show that the ethnic mix of donors to the SCBB has remained generally broad in source, is comparative to the Australian population, and is more diverse than the ABMDR. This, however, may still not be sufficient to substantially increase the likelihood of finding a donor for some ethnic minority groups.

A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells

PubMed Central

Schulz, Thomas C.; Young, Holly Y.; Agulnick, Alan D.; Babin, M. Josephine; Baetge, Emmanuel E.; Bang, Anne G.; Bhoumik, Anindita; Cepa, Igor; Cesario, Rosemary M.; Haakmeester, Carl; Kadoya, Kuniko; Kelly, Jonathan R.; Kerr, Justin; Martinson, Laura A.; McLean, Amanda B.; Moorman, Mark A.; Payne, Janice K.; Richardson, Mike; Ross, Kelly G.; Sherrer, Eric S.; Song, Xuehong; Wilson, Alistair Z.; Brandon, Eugene P.; Green, Chad E.; Kroon, Evert J.; Kelly, Olivia G.; D’Amour, Kevin A.; Robins, Allan J.

2012-01-01

Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50–100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry. PMID:22623968

Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines.

PubMed

Yamamizu, Kohei; Sharov, Alexei A; Piao, Yulan; Amano, Misa; Yu, Hong; Nishiyama, Akira; Dudekula, Dawood B; Schlessinger, David; Ko, Minoru S H

2016-05-06

Mouse embryonic stem cells (ESCs) can differentiate into a wide range - and possibly all cell types in vitro, and thus provide an ideal platform to study systematically the action of transcription factors (TFs) in cell differentiation. Previously, we have generated and analyzed 137 TF-inducible mouse ESC lines. As an extension of this "NIA Mouse ESC Bank," we generated and characterized 48 additional mouse ESC lines, in which single TFs in each line could be induced in a doxycycline-controllable manner. Together, with the previous ESC lines, the bank now comprises 185 TF-manipulable ESC lines (>10% of all mouse TFs). Global gene expression (transcriptome) profiling revealed that the induction of individual TFs in mouse ESCs for 48 hours shifts their transcriptomes toward specific differentiation fates (e.g., neural lineages by Myt1 Isl1, and St18; mesodermal lineages by Pitx1, Pitx2, Barhl2, and Lmx1a; white blood cells by Myb, Etv2, and Tbx6, and ovary by Pitx1, Pitx2, and Dmrtc2). These data also provide and lists of inferred target genes of each TF and possible functions of these TFs. The results demonstrate the utility of mouse ESC lines and their transcriptome data for understanding the mechanism of cell differentiation and the function of TFs.

Constructing an ethical framework for embryo donation to research: is it time for a restricted consent policy?

PubMed

Ehrich, Kathryn; Farsides, Bobbie; Williams, Clare; Scott, Rosamund

2011-06-01

An Ethics & Policy Workshop was held with 20 invited UK stakeholders to consider whether embryo donors should be able to restrict the future use of human embryonic stem cells (hESCs) created from their embryos. Participants cited tensions between pure altruism and a more reciprocal basis for donation; and between basic research (in which genetic material would never form part of another living being) and treatment applications. Two restriction models were suggested to acknowledge specific ethical issues raised by hESCs' use in research and treatments: (1) a two tier system: hESCs with unrestricted consent could go to the UK Stem Cell Bank; those with restricted consent could be used in individual labs which could guarantee to honour the restrictions, and Bank deposit would not be required. (2) a three category system: restrictions could include (i) basic hESC research; (ii) hESC research and treatment; no gamete derivation (iii) 'unrestricted' hESC research and treatment.

Concise Review: One Stone for Multiple Birds: Generating Universally Compatible Human Embryonic Stem Cells.

PubMed

Zheng, Dejin; Wang, Xiaofang; Xu, Ren-He

2016-09-01

With ongoing clinical trials, human embryonic stem cells (hESCs) have shown substantial potential for regenerative medicine. However, due to the mismatch of human leukocyte antigens (HLAs) between hESC-derived allografts and recipients, immunosuppressant regimens must be used to prevent immune rejection of the grafts. Considerable efforts have been devoted to overcoming this hurdle via the derivation and banking of human nuclear transfer ESCs, parthenogenetic ESCs, and induced pluripotent stem cells. However, ethical and safety concerns remain, hindering the application of these types of pluripotent cells. Other approaches have recently been explored to generate universally compatible hESCs through the silencing or deletion of HLAs or genes essential for HLA expression, including β-2-microglobulin and class-II MHC transactivator, as well as the induction of immunosuppression via the ectopic expression of non-classical HLAs (e.g., HLA-E and -G), cytotoxic T lymphocyte antigen 4 fused with immunoglobulin, and programmed death ligand-1. In this review, we introduce developments in this line of research and discuss strategies to reduce the tumorigenic concerns regarding hESCs, especially after they acquire the capability to escape immune surveillance. Stem Cells 2016;34:2269-2275. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Concise Review: The Periosteum: Tapping into a Reservoir of Clinically Useful Progenitor Cells

PubMed Central

Chang, Hana

2012-01-01

Elucidation of the periosteum and its regenerative potential has become a hot topic in orthopedics. Yet few review articles address the unique features of periosteum-derived cells, particularly in light of translational therapies and engineering solutions inspired by the periosteum's remarkable regenerative capacity. This review strives to define periosteum-derived cells in light of cumulative research in the field; in addition, it addresses clinical translation of current insights, hurdles to advancement, and open questions in the field. First, we examine the periosteal niche and its inhabitant cells and the key characteristics of these cells in the context of mesenchymal stem cells and their relevance for clinical translation. We compare periosteum-derived cells with those derived from the marrow niche in in vivo studies, addressing commonalities as well as features unique to periosteum cells that make them potentially ideal candidates for clinical application. Thereafter, we review the differentiation and tissue-building properties of periosteum cells in vitro, evaluating their efficacy in comparison with marrow-derived cells. Finally, we address a new concept of banking periosteum and periosteum-derived cells as a novel alternative to currently available autogenic umbilical blood and perinatal tissue sources of stem cells for today's population of aging adults who were “born too early” to bank their own perinatal tissues. Elucidating similarities and differences inherent to multipotent cells from distinct tissue niches and their differentiation and tissue regeneration capacities will facilitate the use of such cells and their translation to regenerative medicine. PMID:23197852

FogBank: a single cell segmentation across multiple cell lines and image modalities.

PubMed

Chalfoun, Joe; Majurski, Michael; Dima, Alden; Stuelten, Christina; Peskin, Adele; Brady, Mary

2014-12-30

Many cell lines currently used in medical research, such as cancer cells or stem cells, grow in confluent sheets or colonies. The biology of individual cells provide valuable information, thus the separation of touching cells in these microscopy images is critical for counting, identification and measurement of individual cells. Over-segmentation of single cells continues to be a major problem for methods based on morphological watershed due to the high level of noise in microscopy cell images. There is a need for a new segmentation method that is robust over a wide variety of biological images and can accurately separate individual cells even in challenging datasets such as confluent sheets or colonies. We present a new automated segmentation method called FogBank that accurately separates cells when confluent and touching each other. This technique is successfully applied to phase contrast, bright field, fluorescence microscopy and binary images. The method is based on morphological watershed principles with two new features to improve accuracy and minimize over-segmentation. First, FogBank uses histogram binning to quantize pixel intensities which minimizes the image noise that causes over-segmentation. Second, FogBank uses a geodesic distance mask derived from raw images to detect the shapes of individual cells, in contrast to the more linear cell edges that other watershed-like algorithms produce. We evaluated the segmentation accuracy against manually segmented datasets using two metrics. FogBank achieved segmentation accuracy on the order of 0.75 (1 being a perfect match). We compared our method with other available segmentation techniques in term of achieved performance over the reference data sets. FogBank outperformed all related algorithms. The accuracy has also been visually verified on data sets with 14 cell lines across 3 imaging modalities leading to 876 segmentation evaluation images. FogBank produces single cell segmentation from confluent cell sheets with high accuracy. It can be applied to microscopy images of multiple cell lines and a variety of imaging modalities. The code for the segmentation method is available as open-source and includes a Graphical User Interface for user friendly execution.

Germline stem cells: Towards the regeneration of spermatogenesis

PubMed Central

Valli, Hanna; Phillips, Bart T.; Shetty, Gunapala; Byrne, James A.; Clark, Amander T.; Meistrich, Marvin L.; Orwig, Kyle E.

2013-01-01

Improved therapies for cancer and other conditions have resulted in a growing population of long-term survivors. Infertility is an unfortunate side effect of some cancer therapies that impacts the quality of life of survivors who are in their reproductive or pre-reproductive years. Some of these patients have the opportunity to preserve their fertility using standard technologies that include sperm, egg or embryo banking, followed by in vitro fertilization and/or embryo transfer. However, these options are not available to all patients, especially the prepubertal patients who are not yet producing mature gametes. For these patients, there are several stem cell technologies in the research pipeline that may give rise to new fertility options and allow infertile patients to have their own biological children. We will review the role of stem cells in normal spermatogenesis as well as experimental stem cell based techniques that may have potential to generate or regenerate spermatogenesis and sperm. We will present these technologies in the context of the fertility preservation paradigm, but we anticipate that they will have broad implications for the assisted reproduction field. PMID:24314923

Cryopreservation: Vitrification and Controlled Rate Cooling.

PubMed

Hunt, Charles J

2017-01-01

Cryopreservation is the application of low temperatures to preserve the structural and functional integrity of cells and tissues. Conventional cooling protocols allow ice to form and solute concentrations to rise during the cryopreservation process. The damage caused by the rise in solute concentration can be mitigated by the use of compounds known as cryoprotectants. Such compounds protect cells from the consequences of slow cooling injury, allowing them to be cooled at cooling rates which avoid the lethal effects of intracellular ice. An alternative to conventional cooling is vitrification. Vitrification methods incorporate cryoprotectants at sufficiently high concentrations to prevent ice crystallization so that the system forms an amorphous glass thus avoiding the damaging effects caused by conventional slow cooling. However, vitrification too can impose damaging consequences on cells as the cryoprotectant concentrations required to vitrify cells at lower cooling rates are potentially, and often, harmful. While these concentrations can be lowered to nontoxic levels, if the cells are ultra-rapidly cooled, the resulting metastable system can lead to damage through devitrification and growth of ice during subsequent storage and rewarming if not appropriately handled.The commercial and clinical application of stem cells requires robust and reproducible cryopreservation protocols and appropriate long-term, low-temperature storage conditions to provide reliable master and working cell banks. Though current Good Manufacturing Practice (cGMP) compliant methods for the derivation and banking of clinical grade pluripotent stem cells exist and stem cell lines suitable for clinical applications are available, current cryopreservation protocols, whether for vitrification or conventional slow freezing, remain suboptimal. Apart from the resultant loss of valuable product that suboptimal cryopreservation engenders, there is a danger that such processes will impose a selective pressure on the cells selecting out a nonrepresentative, freeze-resistant subpopulation. Optimizing this process requires knowledge of the fundamental processes that occur during the freezing of cellular systems, the mechanisms of damage and methods for avoiding them. This chapter draws together the knowledge of cryopreservation gained in other systems with the current state-of-the-art for embryonic and induced pluripotent stem cell preservation in an attempt to provide the background for future attempts to optimize cryopreservation protocols.

Knowledge and attitudes of pregnant women with regard to collection, testing and banking of cord blood stem cells.

PubMed

Fernandez, Conrad V; Gordon, Kevin; Van den Hof, Michiel; Taweel, Shaureen; Baylis, Françoise

2003-03-18

Umbilical cord blood is used as a source of hematopoietic stem cells for bone marrow transplantation in the treatment of malignant and nonmalignant disease. We sought to examine pregnant women's knowledge and attitudes regarding cord blood banking, as their support is crucial to the success of cord blood transplant programs. A questionnaire examining sociodemographic factors and women's attitudes to cord blood banking was developed on the basis of findings from 2 focus groups and a pilot study. The questionnaire was distributed to 650 women attending antenatal clinics at a regional women's hospital between April and July 2001. A total of 443 women (68%) responded. More than half of the women (307/438 or 70% [95% confidence interval, CI, 66% to 74%]) reported poor or very poor knowledge about cord blood banking. Many of the respondents (299/441 or 68% [95% CI 63% to 72%]) thought that physicians should talk to pregnant women about the collection of cord blood, and they wanted to receive information about this topic from health care professionals (290/441 or 66% [95% CI 61% to 70%]) or prenatal classes (308/441 or 70% [95% CI 65% to 74%]). Most of the women (379/442 or 86% [95% CI 82% to 89%]) would elect to store cord blood in a public bank, many citing altruism as the reason for this choice. A much smaller proportion (63/442 or 14% [95% CI 11% to 18%]) would elect private banking, indicating that this would be a good investment or that they would feel guilty if the blood had not been stored. Additional acceptable uses for cord blood included research (mentioned by 294/436 women or 67% [95% CI 63% to 72%]) and gene therapy (mentioned by 169/437 women or 39% [95% CI 34% to 43%]). Most of the women in this study supported the donation of cord blood to public cord blood banks for potential transplantation and research.

Evaluation of the impact of banking umbilical cord blood units with high cell dose for ethnically diverse patients.

PubMed

Stritesky, Gretta; Wadsworth, Kimberly; Duffy, Merry; Buck, Kelly; Dehn, Jason

2018-02-01

Umbilical cord blood units provide an important stem cell source for transplantation, particularly for patients of ethnic diversity who may not have suitably matched available, adult-unrelated donors. However, with the cost of cord blood unit acquisition from public banks significantly higher than that for adult-unrelated donors, attention is focused on decreasing cost yet still providing cord blood units to patients in need. Historical practices of banking units with low total nucleated cell counts, including units with approximately 90 × 10 7 total nucleated cells, indicates that most banked cord blood units have much lower total nucleated cell counts than are required for transplant. The objective of this study was to determine the impact on the ability to identify suitable cord blood units for transplantation if the minimum total nucleated cell count for banking were increased from 90 × 10 7 to 124 or 149 × 10 7 . We analyzed ethnically diverse patients (median age, 3 years) who underwent transplantation of a single cord blood unit in 2005 to 2016. A cord blood unit search was evaluated to identify units with equal or greater human leukocyte antigen matching and a greater total nucleated cell count than that of the transplanted cord blood unit (the replacement cord blood unit). If the minimum total nucleated cell count for banking increased to 124 or 149 × 10 7 , then from 75 to 80% of patients would still have at least 1 replacement cord blood unit in the current (2016) cord blood unit inventory. The best replacement cord blood units were often found among cords with the same ethnic background as the patient. The current data suggest that, if the minimum total nucleated cell count were increased for banking, then it would likely lead to an inventory of more desirable cord blood units while having minimal impact on the identification of suitable cord blood units for transplantation. © 2017 AABB.

Haemopoietic cell renewal in radiation fields

NASA Astrophysics Data System (ADS)

Fliedner, T. M.; Nothdurft, W.; Tibken, B.; Hofer, E.; Weiss, M.; Kindler, H.

1994-10-01

Space flight activities are inevitably associated with a chronic exposure of astronauts to a complex mixture of ionising radiation. Although no acute radiation consequences are to be expected as a rule, the possibility of Solar Particle Events (SPE) associated with relatively high doses of radiation (1 or more Gray) cannot be excluded. It is the responsibility of physicians in charge of the health of astronauts to evaluate before, during and after space flight activities the functional status of haemopoietic cell renewal. Chronic low level exposure of dogs indicate that daily gamma-exposure doses below about 2 cGy are tolerated for several years as far as blood cell concentrations are concerned. However, the stem cell pool may be severely affected. The maintenance of sufficient blood cell counts is possible only through increased cell production to compensate for the radiation inflicted excess cell loss. This behaviour of haemopoietic cell renewal during chronic low level exposure can be simulated by bioengineering models of granulocytopoiesis. It is possible to define a ``turbulence region'' for cell loss rates, below which an prolonged adaptation to increased radiation fields can be expected to be tolerated. On the basis of these experimental results, it is recommended to develop new biological indicators to monitor haemopoietic cell renewal at the level of the stem cell pool using blood stem cells in addition to the determination of cytokine concentrations in the serum (and other novel approaches). To prepare for unexpected haemopoietic effects during prolonged space missions, research should be increased to modify the radiation sensitivity of haemopoietic stem cells (for instance by the application of certain regulatory molecules). In addition, a ``blood stem cell bank'' might be established for the autologous storage of stem cells and for use in space activities keeping them in a radiation protected container.

Unravelling the mystery of stem/progenitor cells in human breast milk.

PubMed

Fan, Yiping; Chong, Yap Seng; Choolani, Mahesh A; Cregan, Mark D; Chan, Jerry K Y

2010-12-28

Mammary stem cells have been extensively studied as a system to delineate the pathogenesis and treatment of breast cancer. However, research on mammary stem cells requires tissue biopsies which limit the quantity of samples available. We have previously identified putative mammary stem cells in human breast milk, and here, we further characterised the cellular component of human breast milk. We identified markers associated with haemopoietic, mesenchymal and neuro-epithelial lineages in the cellular component of human breast milk. We found 2.6 ± 0.8% (mean ± SEM) and 0.7 ± 0.2% of the whole cell population (WCP) were found to be CD133+ and CD34+ respectively, 27.8 ± 9.1% of the WCP to be positive for Stro-1 through flow-cytometry. Expressions of neuro-ectodermal stem cell markers such as nestin and cytokeratin 5 were found through reverse-transcription polymerase chain reaction (RT-PCR), and in 4.17 ± 0.2% and 0.9 ± 0.2% of the WCP on flow-cytometry. We also established the presence of a side-population (SP) (1.8 ± 0.4% of WCP) as well as CD133+ cells (1.7 ± 0.5% of the WCP). Characterisation of the sorted SP and non-SP, CD133+ and CD133- cells carried out showed enrichment of CD326 (EPCAM) in the SP cells (50.6 ± 8.6 vs 18.1 ± 6.0, P-value  = 0.02). However, culture in a wide range of in vitro conditions revealed the atypical behaviour of stem/progenitor cells in human breast milk; in that if they are present, they do not respond to established culture protocols of stem/progenitor cells. The identification of primitive cell types within human breast milk may provide a non-invasive source of relevant mammary cells for a wide-range of applications; even the possibility of banking one's own stem cell for every breastfeeding woman.

Unravelling the Mystery of Stem/Progenitor Cells in Human Breast Milk

PubMed Central

Fan, Yiping; Chong, Yap Seng; Choolani, Mahesh A.; Cregan, Mark D.; Chan, Jerry K. Y.

2010-01-01

Background Mammary stem cells have been extensively studied as a system to delineate the pathogenesis and treatment of breast cancer. However, research on mammary stem cells requires tissue biopsies which limit the quantity of samples available. We have previously identified putative mammary stem cells in human breast milk, and here, we further characterised the cellular component of human breast milk. Methodology/Principal Findings We identified markers associated with haemopoietic, mesenchymal and neuro-epithelial lineages in the cellular component of human breast milk. We found 2.6±0.8% (mean±SEM) and 0.7±0.2% of the whole cell population (WCP) were found to be CD133+ and CD34+ respectively, 27.8±9.1% of the WCP to be positive for Stro-1 through flow-cytometry. Expressions of neuro-ectodermal stem cell markers such as nestin and cytokeratin 5 were found through reverse-transcription polymerase chain reaction (RT-PCR), and in 4.17±0.2% and 0.9±0.2% of the WCP on flow-cytometry. We also established the presence of a side-population (SP) (1.8±0.4% of WCP) as well as CD133+ cells (1.7±0.5% of the WCP). Characterisation of the sorted SP and non-SP, CD133+ and CD133- cells carried out showed enrichment of CD326 (EPCAM) in the SP cells (50.6±8.6 vs 18.1±6.0, P-value  = 0.02). However, culture in a wide range of in vitro conditions revealed the atypical behaviour of stem/progenitor cells in human breast milk; in that if they are present, they do not respond to established culture protocols of stem/progenitor cells. Conclusions/Significance The identification of primitive cell types within human breast milk may provide a non-invasive source of relevant mammary cells for a wide-range of applications; even the possibility of banking one's own stem cell for every breastfeeding woman. PMID:21203434

Materials for stem cell factories of the future

NASA Astrophysics Data System (ADS)

Celiz, Adam D.; Smith, James G. W.; Langer, Robert; Anderson, Daniel G.; Winkler, David A.; Barrett, David A.; Davies, Martyn C.; Young, Lorraine E.; Denning, Chris; Alexander, Morgan R.

2014-06-01

Polymeric substrates are being identified that could permit translation of human pluripotent stem cells from laboratory-based research to industrial-scale biomedicine. Well-defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large-scale drug-screening programs and clinical use. Yet more than 1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells is challenging, and a rethink of the current predominant cell-derived substrates is needed to provide technology that can be scaled to meet the needs of millions of patients a year. In this Review, we consider the role of materials discovery, an emerging area of materials chemistry that is in large part driven by the challenges posed by biologists to materials scientists.

Bioencapsulation technologies in tissue engineering

PubMed Central

Majewski, Rebecca L.; Zhang, Wujie; Ma, Xiaojun; Cui, Zhanfeng; Ren, Weiping; Markel, David C.

2017-01-01

Bioencapsulation technologies have played an important role in the developing successes of tissue engineering. Besides offering immunoisolation, they also show promise for cell/tissue banking and the directed differentiation of stem cells, by providing a unique microenvironment. This review describes bioencapsulation technologies and summarizes their recent progress in research into tissue engineering. The review concludes with a brief outlook regarding future research directions in this field. PMID:27716872

A novel method to generate and culture human mast cells: Peripheral CD34+ stem cell-derived mast cells (PSCMCs).

PubMed

Schmetzer, Oliver; Valentin, Patricia; Smorodchenko, Anna; Domenis, Rossana; Gri, Giorgia; Siebenhaar, Frank; Metz, Martin; Maurer, Marcus

2014-11-01

The identification and characterization of human mast cell (MC) functions are hindered by the shortage of MC populations suitable for investigation. Here, we present a novel technique for generating large numbers of well differentiated and functional human MCs from peripheral stem cells (=peripheral stem cell-derived MCs, PSCMCs). Innovative and key features of this technique include 1) the use of stem cell concentrates, which are routinely discarded by blood banks, as the source of CD34+ stem cells, 2) cell culture in serum-free medium and 3) the addition of LDL as well as selected cytokines. In contrast to established and published protocols that use CD34+ or CD133+ progenitor cells from full blood, we used a pre-enriched cell population obtained from stem cell concentrates, which yielded up to 10(8) differentiated human MCs per batch after only three weeks of culture starting with 10(6) total CD34+ cells. The total purity on MCs (CD117+, FcεR1+) generated by this method varied between 55 and 90%, of which 4-20% were mature MCs that contain tryptase and chymase and show expression of FcεRI and CD117 in immunohistochemistry. PSCMCs showed robust histamine release in response to stimulation with anti-FcεR1 or IgE/anti-IgE, and increased proliferation and differentiation in response to IL-1β or IFN-γ. Taken together, this new protocol of the generation of large numbers of human MCs provides for an innovative and suitable option to investigate the biology of human MCs. Copyright © 2014 Elsevier B.V. All rights reserved.

ACOG committee opinion number 399, February 2008: umbilical cord blood banking.

PubMed

2008-02-01

Two types of banks have emerged for the collection and storage of umbilical cord blood--public banks and private banks. Public banks promote allogenic (related or unrelated) donation, analogous to the current collection of whole blood units in the United States. Private banks were initially developed to store stem cells from umbilical cord blood for autologous use (taken from an individual for subsequent use by the same individual) by a child if the child develops disease later in life. If a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public versus private banking should be provided. The remote chance of an autologous unit of umbilical cord blood being used for a child or a family member (approximately 1 in 2,700 individuals) should be disclosed. The collection should not alter routine practice for the timing of umbilical cord clamping. Physicians or other professionals who recruit pregnant women and their families for for-profit umbilical cord blood banking should disclose any financial interests or other potential conflicts of interest.

Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood

PubMed Central

Kurtzberg, Joanne; Lyerly, Anne Drapkin; Sugarman, Jeremy

2005-01-01

Since the first successful transplantation of umbilical cord blood in 1988, cord blood has become an important source of hematopoietic stem and progenitor cells for the treatment of blood and genetic disorders. Significant progress has been accompanied by challenges for scientists, ethicists, and health policy makers. With the recent recognition of the need for a national system for the collection, banking, distribution, and use of cord blood and the increasing focus on cord blood as an alternative to embryos as a source of tissue for regenerative medicine, cord blood has garnered significant attention. We review the development of cord blood banking and transplantation and then discuss the scientific and ethical issues influencing both established and investigational practices surrounding cord blood collection, banking, and use. PMID:16200191

A new strategy for umbilical cord blood collection developed at the first Colombian public cord blood bank increases total nucleated cell content.

PubMed

Vanegas, Diana; Triviño, Lady; Galindo, Cristian; Franco, Leidy; Salguero, Gustavo; Camacho, Bernardo; Perdomo-Arciniegas, Ana-María

2017-09-01

The total nucleated cell dosage of umbilical cord blood (UCB) is an important factor in determining successful allogeneic hematopoietic stem cell transplantation after a minimum human leukocyte antigen donor-recipient match. The northern South American population is in need of a new-generation cord blood bank that cryopreserves only units with high total nucleated cell content, thereby increasing the likelihood of use. Colombia set up a public cord blood bank in 2014; and, as a result of its research for improving high total nucleated cell content, a new strategy for UCB collection was developed. Data from 2933 collected and 759 cryopreserved cord blood units between 2014 and 2015 were analyzed. The correlation of donor and collection variables with cellularity was evaluated. Moreover, blood volume, cell content, CD34+ count, clonogenic capacity, and microbial contamination were assessed comparing the new method, which combines in utero and ex utero techniques, with the conventional strategies. Multivariate analysis confirmed a correlation between neonatal birth weight and cell content. The new collection method increased total nucleated cell content in approximately 26% and did not alter pre-cryopreservation and post-thaw cell recovery, viability, or clonogenic ability. Furthermore, it showed a remarkably low microbial contamination rate (1.2%). The strategy for UCB collection developed at the first Colombian public cord blood bank increases total nucleated cell content and does not affect unit quality. The existence of this bank is a remarkable breakthrough for Latin-American patients in need of this kind of transplantation. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Expansion and Differentiation of Germline-Derived Pluripotent Stem Cells on Biomaterials

PubMed Central

Šarić, Tomo; Denecke, Bernd; Peinkofer, Gabriel; Bovi, Manfred; Groll, Jürgen; Ko, Kinarm; Salber, Jochen; Halbach, Marcel; Schöler, Hans R.; Zenke, Martin; Neuss, Sabine

2013-01-01

Stem cells with broad differentiation potential, such as the recently described germline-derived pluripotent stem cells (gPS cells), are an appealing source for tissue engineering strategies. Biomaterials can inhibit, support, or induce proliferation and differentiation of stem cells. Here we identified (1) polymers that maintain self-renewal and differentiation potential of gPS cells for feeder-free expansion and (2) polymers supporting the cardiomyogenic fate of gPS cells by analyzing a panel of polymers of an established biomaterial bank previously used to assess growth of diverse stem cell types. Identification of cytocompatible gPS cell/biomaterial combinations required analysis of several parameters, including morphology, viability, cytotoxicity, apoptosis, proliferation, and differentiation potential. Pluripotency of gPS cells was visualized by the endogenous Oct4-promoter-driven GFP and by Sox2 and Nanog immunofluorescence. Viability assay, proliferation assay, and flow cytometry showed that gPS cells efficiently adhere and are viable on synthetic polymers, such as Resomer® LR704 (poly(L-lactic-D,L-lactic acid), poly(tetrafluor ethylene) (PTFE), poly(vinylidene fluoride) (PVDF), and on gelatine-coated tissue culture polystyrene. Expansion experiments showed that Resomer LR704 is an alternative substrate for feeder-free gPS cell maintenance. Resomer LR704, PTFE, and PVDF were found to be suitable for gPS cell differentiation. Spontaneous beating in embryoid bodies cultured on Resomer LR704 occurred already on day 8 of differentiation, much earlier compared to the other surfaces. This indicates that Resomer LR704 supports spontaneous cardiomyogenic differentiation of gPS cells, which was also confirmed on molecular, protein and functional level. PMID:23234562

Expansion and differentiation of germline-derived pluripotent stem cells on biomaterials.

PubMed

Hoss, Mareike; Šarić, Tomo; Denecke, Bernd; Peinkofer, Gabriel; Bovi, Manfred; Groll, Jürgen; Ko, Kinarm; Salber, Jochen; Halbach, Marcel; Schöler, Hans R; Zenke, Martin; Neuss, Sabine

2013-05-01

Stem cells with broad differentiation potential, such as the recently described germline-derived pluripotent stem cells (gPS cells), are an appealing source for tissue engineering strategies. Biomaterials can inhibit, support, or induce proliferation and differentiation of stem cells. Here we identified (1) polymers that maintain self-renewal and differentiation potential of gPS cells for feeder-free expansion and (2) polymers supporting the cardiomyogenic fate of gPS cells by analyzing a panel of polymers of an established biomaterial bank previously used to assess growth of diverse stem cell types. Identification of cytocompatible gPS cell/biomaterial combinations required analysis of several parameters, including morphology, viability, cytotoxicity, apoptosis, proliferation, and differentiation potential. Pluripotency of gPS cells was visualized by the endogenous Oct4-promoter-driven GFP and by Sox2 and Nanog immunofluorescence. Viability assay, proliferation assay, and flow cytometry showed that gPS cells efficiently adhere and are viable on synthetic polymers, such as Resomer(®) LR704 (poly(L-lactic-D,L-lactic acid), poly(tetrafluor ethylene) (PTFE), poly(vinylidene fluoride) (PVDF), and on gelatine-coated tissue culture polystyrene. Expansion experiments showed that Resomer LR704 is an alternative substrate for feeder-free gPS cell maintenance. Resomer LR704, PTFE, and PVDF were found to be suitable for gPS cell differentiation. Spontaneous beating in embryoid bodies cultured on Resomer LR704 occurred already on day 8 of differentiation, much earlier compared to the other surfaces. This indicates that Resomer LR704 supports spontaneous cardiomyogenic differentiation of gPS cells, which was also confirmed on molecular, protein and functional level.

ROCK inhibitor Y-27632 increases thaw-survival rates and preserves stemness and differentiation potential of human Wharton's jelly stem cells after cryopreservation.

PubMed

Gauthaman, Kalamegam; Fong, Chui-Yee; Subramanian, Arjunan; Biswas, Arijit; Bongso, Ariff

2010-12-01

The ROCK inhibitor Y-27632 inhibits apoptosis and increases proliferation of frozen-thawed cells. We examined the role of Y-27632 on human umbilical cord Wharton's jelly stem cells (hWJSCs) for (1) thaw-survival (2) proliferation and (3) preservation of stemness and differentiation potential after cryopreservation. hWJSCs were allotted to 4 groups [Gp I: Untreated hWJSC controls; Gp II: Pretreatment with Y-27632 (10 μM) for 24 h before freezing; Gp III: Y-27632 (10 μM) in freezing medium and Gp IV: Pretreatment with Y-27632 (10 μM) for 24 h and inclusion in freezing medium]. All groups were frozen using a rapid freezing method and stored at -196°C in liquid nitrogen for 90 days before evaluation for apoptosis, cell proliferation, stemness and differentiation. After thawing, Groups II, III and IV showed improved cell attachment, increased thaw-survival (live/dead cell counts) and increased cell proliferation (Trypan blue and MTT assay) compared to controls. CD marker stemness profiles, morphology and normal karyotypes were maintained in the treatment groups after thawing and there was no obvious evidence of apoptosis (Annexin V-FITC and TUNEL assays). After thawing, qRT-PCR demonstrated up-regulation of the anti-apoptotic BCL2 gene and down-regulation of the pro-apoptotic BAX gene and cell cycle regulators (P53 and P21) in the treatment groups. Treated frozen-thawed hWJSCs from all groups differentiated into a neuronal phenotype (neuronal morphology and expression of GFAP, β-3 tubulin and SOX2). Increased thaw-survival and retention of stemness and differentiation potential in hWJSCs following cryopreservation is useful for their storage in cord blood banks for future regenerative medicine purposes.

Genome Resource Banking of Biomedically Important Laboratory Animals

PubMed Central

Agca, Yuksel

2014-01-01

Genome resource banking (GRB) is the systematic collection, storage, and re-distribution of biomaterials in an organized, logistical, and secure manner. Genome cyrobanks usually contain biomaterials and associated genomic information essential for progression of biomedicine, human health, and research. In that regard, appropriate genome cryobanks could provide essential biomaterials for both current and future research projects in the form of various cell types and tissues, including sperm, oocytes, embryos, embryonic or adult stem cells, induced pluripotent stem cells, and gonadal tissues. In addition to cryobanked germplasm, cryobanking of DNA, serum, blood products, and tissues from scientifically, economically and ecologically important species has become a common practice. For revitalization of the whole organism, cryopreserved germplasm in conjunction with assisted reproductive technologies (ART), offer a powerful approach for research model management, as well as assisting in animal production for agriculture, conservation, and human reproductive medicine. Recently, many developed and developing countries have allocated substantial resources to establish genome resources banks which are responsible for safeguarding scientifically, economically and ecologically important wild type, mutant and transgenic plants, fish, and local livestock breeds, as well as wildlife species. This review is dedicated to the memory of Dr. John K. Critser, who had made profound contributions to the science of cryobiology and establishment of genome research and resources centers for mice, rats and swine. Emphasis will be given to application of GRBs to species with substantial contributions to the advancement of biomedicine and human health. PMID:22981880

Umbilical cord blood banking and the next generation of human tissue regulation: an agenda for research.

PubMed

Stewart, Cameron; Kerridge, Ian

2012-03-01

The transformation of umbilical cord blood from being a waste product to being a valuable source of stem cells has led to the emergence of significant legal, ethical and social issues. This editorial proposes an agenda for research into the regulation of umbilical cord blood banking which focuses on issues of characterisation, consent, the interplay of public and private services, and the importance of applying property concepts. It concludes by stressing the need for reform to be based on well-informed public debate.

Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes

PubMed Central

Dekimpe, Emily; Van Woensel, Matthias; Roobrouck, Valerie D.; Bullens, Dominique M.; Pinxteren, Jef; Verfaillie, Catherine M.; Van Gool, Stefaan W.

2016-01-01

MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8+ cytotoxic T lymphocytes (CTLs) was addressed for the first time. In an in vitro setting, the immunogenicity of MultiStem, the susceptibility of MultiStem toward CTL-mediated lysis, and its effects on CTL function were investigated. MultiStem was nonimmunogenic for alloreactive CTL induction and was—even after major histocompatibility complex class I upregulation—insensitive to alloantigen-specific CTL-mediated lysis. Furthermore, MultiStem reduced CTL proliferation and significantly decreased perforin expression during the T-cell activation phase. As a consequence, MultiStem dose-dependently impaired the induction of CTL function. These effects of MultiStem were mediated predominantly through contact-dependent mechanisms. Moreover, MultiStem cells considerably influenced the expression of T-cell activation markers CD25, CD69, and human leukocyte antigen-DR. The MultiStem-induced CD8−CD69+ T-cell population displayed a suppressive effect on the induction of CTL function during a subsequent mixed-lymphocyte culture. Finally, the killer activity of activated antigen-specific CTLs during their cytolytic effector phase was also diminished in the presence of MultiStem. This study confirms that these clinical-grade MAPCs are an immune-modulating population that inhibits CTL activation and effector responses and are, consequently, a highly valuable cell population for adoptive immunosuppressive therapy in diseases where damage is induced by CTLs. Significance Because multipotent adult progenitor cells (MAPCs) are among the noteworthy adult mesenchymal stem cell populations for immune therapy and have the advantage over mesenchymal stem cells (MSCs) of large-scale manufacturing and banking potential and thus prompt availability, it is important to understand how MAPCs interact with immune cells to validate their widespread therapeutic applicability. Cytotoxic immune effector cells play a crucial role in immune homeostasis and in the pathogenesis of some autoimmune diseases. This study assessed for the first time the in vitro influence of a clinical-grade human MAPC product (MultiStem) on the cytotoxic function of CD8+ T cells (CTLs) by evaluating the immunogenicity of MAPCs and the susceptibility of MAPCs toward CTL-mediated lysis and by analyzing the mechanism of MAPC-mediated modulation of CTL functionality. These results may represent a highly relevant contribution to the current knowledge and, in combination with the results of future phase II/III trials using MultiStem, could lead to an intriguing continuation of stem cell-based research for immunotherapy. PMID:27465071

Clinical-Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes.

PubMed

Plessers, Jeroen; Dekimpe, Emily; Van Woensel, Matthias; Roobrouck, Valerie D; Bullens, Dominique M; Pinxteren, Jef; Verfaillie, Catherine M; Van Gool, Stefaan W

2016-12-01

: MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8 + cytotoxic T lymphocytes (CTLs) was addressed for the first time. In an in vitro setting, the immunogenicity of MultiStem, the susceptibility of MultiStem toward CTL-mediated lysis, and its effects on CTL function were investigated. MultiStem was nonimmunogenic for alloreactive CTL induction and was-even after major histocompatibility complex class I upregulation-insensitive to alloantigen-specific CTL-mediated lysis. Furthermore, MultiStem reduced CTL proliferation and significantly decreased perforin expression during the T-cell activation phase. As a consequence, MultiStem dose-dependently impaired the induction of CTL function. These effects of MultiStem were mediated predominantly through contact-dependent mechanisms. Moreover, MultiStem cells considerably influenced the expression of T-cell activation markers CD25, CD69, and human leukocyte antigen-DR. The MultiStem-induced CD8 - CD69 + T-cell population displayed a suppressive effect on the induction of CTL function during a subsequent mixed-lymphocyte culture. Finally, the killer activity of activated antigen-specific CTLs during their cytolytic effector phase was also diminished in the presence of MultiStem. This study confirms that these clinical-grade MAPCs are an immune-modulating population that inhibits CTL activation and effector responses and are, consequently, a highly valuable cell population for adoptive immunosuppressive therapy in diseases where damage is induced by CTLs. Because multipotent adult progenitor cells (MAPCs) are among the noteworthy adult mesenchymal stem cell populations for immune therapy and have the advantage over mesenchymal stem cells (MSCs) of large-scale manufacturing and banking potential and thus prompt availability, it is important to understand how MAPCs interact with immune cells to validate their widespread therapeutic applicability. Cytotoxic immune effector cells play a crucial role in immune homeostasis and in the pathogenesis of some autoimmune diseases. This study assessed for the first time the in vitro influence of a clinical-grade human MAPC product (MultiStem) on the cytotoxic function of CD8 + T cells (CTLs) by evaluating the immunogenicity of MAPCs and the susceptibility of MAPCs toward CTL-mediated lysis and by analyzing the mechanism of MAPC-mediated modulation of CTL functionality. These results may represent a highly relevant contribution to the current knowledge and, in combination with the results of future phase II/III trials using MultiStem, could lead to an intriguing continuation of stem cell-based research for immunotherapy. ©AlphaMed Press.

Can Human Embryonic Stem Cell-Derived Stromal Cells Serve a Starting Material for Myoblasts?

PubMed Central

Ando, Yu; Saito, Marie; Machida, Masakazu; Yoshida-Noro, Chikako; Akutsu, Hidenori; Takahashi, Masataka

2017-01-01

A large number of myocytes are necessary to treat intractable muscular disorders such as Duchenne muscular dystrophy with cell-based therapies. However, starting materials for cellular therapy products such as myoblasts, marrow stromal cells, menstrual blood-derived cells, and placenta-derived cells have a limited lifespan and cease to proliferate in vitro. From the viewpoints of manufacturing and quality control, cells with a long lifespan are more suitable as a starting material. In this study, we generated stromal cells for future myoblast therapy from a working cell bank of human embryonic stem cells (ESCs). The ESC-derived CD105+ cells with extensive in vitro proliferation capability exhibited myogenesis and genetic stability in vitro. These results imply that ESC-derived CD105+ cells are another cell source for myoblasts in cell-based therapy for patients with genetic muscular disorders. Since ESCs are immortal, mesenchymal stromal cells generated from ESCs can be manufactured at a large scale in one lot for pharmaceutical purposes. PMID:28706537

Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

PubMed

Rafii, Shahin; Ginsberg, Michael; Scandura, Joseph; Butler, Jason M; Ding, Bi-Sen

2016-08-01

Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This approach provides a path to therapeutic EC transplantation that can be infused concomitantly or sequentially with hematopoietic stem cell transplantation more than 24 h after irradiation to support multi-organ regeneration, thereby improving immediate and long-term survival, while limiting long-term morbidity resulting from nonregenerative damage repair pathways.

Functional melanocytes derived from human pluripotent stem cells engraft into pluristratified epidermis.

PubMed

Nissan, Xavier; Larribere, Lionel; Saidani, Manoubia; Hurbain, Ilse; Delevoye, Cédric; Feteira, Jessica; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

2011-09-06

Melanocytes are essential for skin homeostasis and protection, and their defects in humans lead to a wide array of diseases that are potentially extremely severe. To date, the analysis of molecular mechanisms and the function of human melanocytes have been limited because of the difficulties in accessing large numbers of cells with the specific phenotypes. This issue can now be addressed via a differentiation protocol that allows melanocytes to be obtained from pluripotent stem cell lines, either induced or of embryonic origin, based on the use of moderate concentrations of a single cytokine, bone morphogenic protein 4. Human melanocytes derived from pluripotent stem cells exhibit all the characteristic features of their adult counterparts. This includes the enzymatic machinery required for the production and functional delivery of melanin to keratinocytes. Melanocytes also integrate appropriately into organotypic epidermis reconstructed in vitro. The availability of human cells committed to the melanocytic lineage in vitro will enable the investigation of those mechanisms that guide the developmental processes and will facilitate analysis of the molecular mechanisms responsible for genetic diseases. Access to an unlimited resource may also prove a vital tool for the treatment of hypopigmentation disorders when donors with matching haplotypes become available in clinically relevant banks of pluripotent stem cell lines.

Umbilical Cord Blood: Information for Childbirth Educators

PubMed Central

Waller-Wise, Renece

2011-01-01

Umbilical cord blood was once thought of as a waste product. Now, years after the first successful umbilical cord blood transplant, more families seek information about whether or not to save their newborn’s cord blood. Childbirth educators may be one of the main sources that an expectant family depends on to gain more knowledge about cord blood banking in order to make an informed decision. Preserving umbilical cord blood in public banks is advisable for any family; however, it is recommended that expectant families only consider private cord blood banking when they have a relative with a known disorder that is treatable by stem cell transplants. The childbirth educator is encouraged to be well versed on the topic of cord blood banking, so that as questions from class participants arise, the topic can be explored and addressed appropriately. PMID:22211060

Methods for the identification, characterization and banking of human DPSCs: current strategies and perspectives.

PubMed

Tirino, Virginia; Paino, Francesca; d'Aquino, Riccardo; Desiderio, Vincenzo; De Rosa, Alfredo; Papaccio, Gianpaolo

2011-09-01

Dental pulp stem cells (DPSCs), originating from neural crests, can be found within dental pulp. Up to now, it has been demonstrated that these cells are capable of producing bone tissue, both in vitro and in vivo and differentiate into adipocytes, endotheliocytes, melanocytes, neurons, glial cells, and can be easily cryopreserved and stored. Moreover, recent attention has been focused on tissue engineering and on the properties of these cells. In addition, adult bone tissue with good vascularisation has been obtained in grafts. The latest use in clinical trials for bone repair enforces the notion that DPSCs can be used successfully in patients. Therefore, their isolation, selection, differentiation and banking is of great importance. The isolation and detection techniques used in most laboratories are based on the use of antibodies revealed by flow-cytometers with cell sorter termed FACS (fluorescent activated cell sorter). In this report, we focus our attention on the main procedures used in the selection of DPSCs by flow cytometry, cell culture, freezing/thawing, cell cycle evaluation, histochemistry/immunofluorescence and differentiation of DPSCs. In addition, new methods/protocols to select and isolate stem cells without staining by fluorescent markers for implementation in biomedical/clinical laboratories are discuss. We emphasize that the new methods must address simplicity and short times of preparation and use of samples, complete sterility of cells, the potential disposable, low cost and complete maintenance of the viability and integrity of the cells with real-time response for subsequent applications in the biomedical/clinical/surgical fields.

Effect of Antioxidants and Apoptosis Inhibitors on Cryopreservation of Murine Germ Cells Enriched for Spermatogonial Stem Cells.

PubMed

Ha, Seung-Jung; Kim, Byung-Gak; Lee, Yong-An; Kim, Yong-Hee; Kim, Bang-Jin; Jung, Sang-Eun; Pang, Myeong-Geol; Ryu, Buom-Yong

2016-01-01

Spermatogonial stem cells (SSCs) are germline stem cells that serve as the foundation of spermatogenesis to maintain fertility throughout a male's lifetime. To treat male infertility using stem cell banking systems and transplantation, it is important to be able to preserve SSCs for long periods of time. Therefore, this study was conducted to develop an optimal cryopreservation protocol for SSCs using antioxidants and apoptosis inhibitors in freezing medium. No differences were observed compared to controls when SSCs were cryopreserved in the presence of apoptosis inhibitors by themselves. However, mouse germ cells cryopreserved in basal medium containing the antioxidant hypotaurine (14 mM) resulted in significantly greater proliferation potential and mitochondrial activity. Furthermore, treatment groups with combinations containing 200 mM trehalose and 14 mM hypotaurine showed higher proliferation rates compared to controls. In addition, several serum free conditions were evaluated for SSC cryopreservation. Treatment media containing 10% or 20% knockout serum replacement resulted in similar cryopreservation results compared to media containing FBS. SSC transplantation was also performed to confirm the functionality of SSCs frozen in 14 mM hypotaurine. Donor SSCs formed normal spermatogenic colonies and sperm in the recipient testis. These data indicate that inclusion of 14 mM hypotaurine in cryopreservation media is an effective way to efficiently cryopreserve germ cells enriched for SSCs and that knockout serum replacement can replace FBS in germ cell cryopreservation media.

Molecular Cloning and Characterization of DXS and DXR Genes in the Terpenoid Biosynthetic Pathway of Tripterygium wilfordii

PubMed Central

Tong, Yuru; Su, Ping; Zhao, Yujun; Zhang, Meng; Wang, Xiujuan; Liu, Yujia; Zhang, Xianan; Gao, Wei; Huang, Luqi

2015-01-01

1-Deoxy-d-xylulose-5-phosphate synthase (DXS) and 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) genes are the key enzyme genes of terpenoid biosynthesis but still unknown in Tripterygium wilfordii Hook. f. Here, three full-length cDNA encoding DXS1, DXS2 and DXR were cloned from suspension cells of T. wilfordii with ORF sizes of 2154 bp (TwDXS1, GenBank accession no.KM879187), 2148 bp (TwDXS2, GenBank accession no.KM879186), 1410 bp (TwDXR, GenBank accession no.KM879185). And, the TwDXS1, TwDXS2 and TwDXR were characterized by color complementation in lycopene accumulating strains of Escherichia coli, which indicated that they encoded functional proteins and promoted lycopene pathway flux. TwDXS1 and TwDXS2 are constitutively expressed in the roots, stems and leaves and the expression level showed an order of roots > stems > leaves. After the suspension cells were induced by methyl jasmonate, the mRNA expression level of TwDXS1, TwDXS2, and TwDXR increased, and triptophenolide was rapidly accumulated to 149.52 µg·g−1, a 5.88-fold increase compared with the control. So the TwDXS1, TwDXS2, and TwDXR could be important genes involved in terpenoid biosynthesis in Tripterygium wilfordii Hook. f. PMID:26512659

Optimising methods of red cell sedimentation from cord blood to maximise nucleated cell recovery prior to cryopreservation.

PubMed

Madkaikar, M; Gupta, M; Ghosh, K; Swaminathan, S; Sonawane, L; Mohanty, D

2007-01-01

Human cord blood is now an established source of stem cells for haematopoietic reconstitution. Red blood cell (RBC) depletion is required to reduce the cord blood unit volume for commercial banking. Red cell sedimentation using hydroxy ethyl starch (HES) is a standard procedure in most cord blood banks. However, while standardising the procedure for cord blood banking, a significant loss of nucleated cells (NC) may be encountered during standard HES sedimentation protocols. This study compares four procedures for cord blood processing to obtain optimal yield of nucleated cells. Gelatin, dextran, 6% HES and 6% HES with an equal volume of phosphate-buffered saline (PBS) were compared for RBC depletion and NC recovery. Dilution of the cord blood unit with an equal volume of PBS prior to sedimentation with HES resulted in maximum NC recovery (99% [99.5 +/- 1.3%]). Although standard procedures using 6% HES are well established in Western countries, they may not be applicable in India, as a variety of factors that can affect RBC sedimentation (e.g., iron deficiency, hypoalbuminaemia, thalassaemia trait, etc.) may reduce RBC sedimentation and thus reduce NC recovery. While diluting cord blood with an equal volume of PBS is a simple method to improve the NC recovery, it does involve an additional processing step.

Knowledge and attitudes of pregnant women with regard to collection, testing and banking of cord blood stem cells

PubMed Central

Fernandez, Conrad V.; Gordon, Kevin; Hof, Michiel Van den; Taweel, Shaureen; Baylis, Françoise

2003-01-01

Background Umbilical cord blood is used as a source of hematopoietic stem cells for bone marrow transplantation in the treatment of malignant and nonmalignant disease. We sought to examine pregnant women's knowledge and attitudes regarding cord blood banking, as their support is crucial to the success of cord blood transplant programs. Methods A questionnaire examining sociodemographic factors and women's attitudes to cord blood banking was developed on the basis of findings from 2 focus groups and a pilot study. The questionnaire was distributed to 650 women attending antenatal clinics at a regional women's hospital between April and July 2001. Results A total of 443 women (68%) responded. More than half of the women (307/438 or 70% [95% confidence interval, CI, 66% to 74%]) reported poor or very poor knowledge about cord blood banking. Many of the respondents (299/441 or 68% [95% CI 63% to 72%]) thought that physicians should talk to pregnant women about the collection of cord blood, and they wanted to receive information about this topic from health care professionals (290/441 or 66% [95% CI 61% to 70%]) or prenatal classes (308/441 or 70% [95% CI 65% to 74%]). Most of the women (379/442 or 86% [95% CI 82% to 89%]) would elect to store cord blood in a public bank, many citing altruism as the reason for this choice. A much smaller proportion (63/442 or 14% [95% CI 11% to 18%]) would elect private banking, indicating that this would be a good investment or that they would feel guilty if the blood had not been stored. Additional acceptable uses for cord blood included research (mentioned by 294/436 women or 67% [95% CI 63% to 72%]) and gene therapy (mentioned by 169/437 women or 39% [95% CI 34% to 43%]). Interpretation Most of the women in this study supported the donation of cord blood to public cord blood banks for potential transplantation and research. PMID:12642424

Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro.

PubMed

Ozaki, Masahiro; Iwanami, Akio; Nagoshi, Narihito; Kohyama, Jun; Itakura, Go; Iwai, Hiroki; Nishimura, Soraya; Nishiyama, Yuichiro; Kawabata, Soya; Sugai, Keiko; Iida, Tsuyoshi; Matsubayashi, Kohei; Isoda, Miho; Kashiwagi, Rei; Toyama, Yoshiaki; Matsumoto, Morio; Okano, Hideyuki; Nakamura, Masaya

2017-03-01

To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries. In this study, we evaluated the significance of HLA matching in hiPSC-NS/PC transplantation by performing modified mixed lymphocyte reaction (MLR) assays with hiPSC-NS/PCs. Compared to fetus-derived NS/PCs, the expression levels of human leukocyte antigen-antigen D related (HLA-DR) and co-stimulatory molecules on hiPSC-NS/PCs were significantly low, even with the addition of tumor necrosis factor-α (TNFα) and/or interferon-γ (IFNγ) to mimic the inflammatory environment surrounding transplanted hiPSC-NS/PCs in injured tissues. Interestingly, both the allogeneic HLA-matched and the HLA-mismatched responses were similarly low in the modified MLR assay. Furthermore, the autologous response was also similar to the allogeneic response. hiPSC-NS/PCs suppressed the proliferative responses of allogeneic HLA-mismatched peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Thus, the low antigen-presenting function and immunosuppressive effects of hiPSC-NS/PCs result in a depressed immune response, even in an allogeneic HLA-mismatched setting. It is crucial to verify whether these in vitro results are reproducible in a clinical setting. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Isolation and characterization of the environmental bacterial and fungi contamination in a pharmaceutical unit of mesenchymal stem cell for clinical use.

PubMed

Martín, Patricia Gálvez; González, María Bermejo; Martínez, Adolfina Ruiz; Lara, Visitación Gallardo; Naveros, Beatriz Clares

2012-09-01

Design and implementation of an environmental monitoring program is vital to assure the maintenance of acceptable quality conditions in a pharmaceutical manufacturing unit of human mesenchymal stem cells. Since sterility testing methods require 14 days and these cells are only viable for several hours, they are currently administered without the result of this test. Consequently environmental monitoring is a key element in stem cell banks for assuring low levels of potential introduction of contaminants into the cell products. The aim of this study was to qualitatively and quantitatively analyze the environmental microbiological quality in a pharmaceutical manufacturing unit of human mesenchymal stem cells production for use in advanced therapies. Two hundred and sixty one points were tested monthly during one year, 156 from air and 105 from surfaces. Among the 6264 samples tested, 231 showed contamination, 76.6% for bacteria and 23.4% for fungi. Microbial genuses isolated were Staphylococcus (89.7%), Microccocus (4.5%), Kocuria (3.2%) and Bacillus (2.6%). In the identification of fungi, three genuses were detected: Aspergillus (56%), Penicillium (26%) and Cladosporium (18%). The origin of the contamination was found to be due to personnel manipulation and air microbiota. For all sampling methods, alert limits were set and corrective measures suggested. Copyright © 2012 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Effect of Antioxidants and Apoptosis Inhibitors on Cryopreservation of Murine Germ Cells Enriched for Spermatogonial Stem Cells

PubMed Central

Lee, Yong-An; Kim, Yong-Hee; Kim, Bang-Jin; Jung, Sang-Eun; Pang, Myeong-Geol; Ryu, Buom-Yong

2016-01-01

Spermatogonial stem cells (SSCs) are germline stem cells that serve as the foundation of spermatogenesis to maintain fertility throughout a male’s lifetime. To treat male infertility using stem cell banking systems and transplantation, it is important to be able to preserve SSCs for long periods of time. Therefore, this study was conducted to develop an optimal cryopreservation protocol for SSCs using antioxidants and apoptosis inhibitors in freezing medium. No differences were observed compared to controls when SSCs were cryopreserved in the presence of apoptosis inhibitors by themselves. However, mouse germ cells cryopreserved in basal medium containing the antioxidant hypotaurine (14 mM) resulted in significantly greater proliferation potential and mitochondrial activity. Furthermore, treatment groups with combinations containing 200 mM trehalose and 14 mM hypotaurine showed higher proliferation rates compared to controls. In addition, several serum free conditions were evaluated for SSC cryopreservation. Treatment media containing 10% or 20% knockout serum replacement resulted in similar cryopreservation results compared to media containing FBS. SSC transplantation was also performed to confirm the functionality of SSCs frozen in 14 mM hypotaurine. Donor SSCs formed normal spermatogenic colonies and sperm in the recipient testis. These data indicate that inclusion of 14 mM hypotaurine in cryopreservation media is an effective way to efficiently cryopreserve germ cells enriched for SSCs and that knockout serum replacement can replace FBS in germ cell cryopreservation media. PMID:27548381

Induced Pluripotent Stem Cell-Derived Red Blood Cells and Platelet Concentrates: From Bench to Bedside.

PubMed

Focosi, Daniele; Amabile, Giovanni

2017-12-27

Red blood cells and platelets are anucleate blood components indispensable for oxygen delivery and hemostasis, respectively. Derivation of these blood elements from induced pluripotent stem (iPS) cells has the potential to develop blood donor-independent and genetic manipulation-prone products to complement or replace current transfusion banking, also minimizing the risk of alloimmunization. While the production of erythrocytes from iPS cells has challenges to overcome, such as differentiation into adult-type phenotype that functions properly after transfusion, platelet products are qualitatively and quantitatively approaching a clinically-applicable level owing to advances in expandable megakaryocyte (MK) lines, platelet-producing bioreactors, and novel reagents. Guidelines that assure the quality of iPS cells-derived blood products for clinical application represent a novel challenge for regulatory agencies. Considering the minimal risk of tumorigenicity and the expected significant demand of such products, ex vivo production of iPS-derived blood components can pave the way for iPS translation into the clinic.

Family-directed umbilical cord blood banking

PubMed Central

Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M.

2011-01-01

Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available. PMID:21750089

Family-directed umbilical cord blood banking.

PubMed

Gluckman, Eliane; Ruggeri, Annalisa; Rocha, Vanderson; Baudoux, Etienne; Boo, Michael; Kurtzberg, Joanne; Welte, Kathy; Navarrete, Cristina; van Walraven, Suzanna M

2011-11-01

Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available.

Concomitant differentiation of a population of mouse embryonic stem cells into neuron-like cells and Schwann cell-like cells in a slow-flow microfluidic device

PubMed Central

Ramamurthy, Poornapriya; White, Joshua B.; Park, Joong Yull; Hume, Richard I.; Ebisu, Fumi; Mendez, Flor; Takayama, Shuichi; Barald, Kate F

2016-01-01

Background To send meaningful information to the brain, an inner ear cochlear implant (CI) must become closely coupled to as large and healthy a population of remaining Spiral Ganglion Neurons (SGN) as possible. Inner ear gangliogenesis depends on macrophage migration inhibitory factor (MIF), a directionally attractant neurotrophic cytokine made by both Schwann and supporting cells (Bank et al., 2012). MIF-induced mouse embryonic stem cell (mESC)-derived “neurons” could potentially substitute for lost or damaged SGN. mESC-derived “Schwann cells” produce MIF as do all Schwann cells (Huang et al., 2002; Roth et al., 2007, 2008) and could attract SGN to “ cell coated” implant. Results Neuron- and Schwann cell-like cells were produced from a common population of mESC in an ultra-slow flow microfluidic device. As the populations interacted; “neurons” grew over the “Schwann cell” lawn and early events in myelination were documented. Blocking MIF on the Schwann cell side greatly reduced directional neurite outgrowth. MIF-expressing “Schwann cells” were used to “coat” a CI: mouse SGN and MIF-induced “neurons” grew directionally to the CI and to a wild type but not MIF-knock out Organ of Corti explant. Conclusions Two novel stem cell-based approaches for treating the problem of sensorineural hearing loss are described. PMID:27761977

Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective.

PubMed

Beak, Carla Pereira; Chargé, Sophie B; Isasi, Rosario; Knoppers, Bartha M

2015-05-01

In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS-in collaboration with researchers from the Stem Cell Network-have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.

Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications.

PubMed

Baghbaderani, Behnam Ahmadian; Syama, Adhikarla; Sivapatham, Renuka; Pei, Ying; Mukherjee, Odity; Fellner, Thomas; Zeng, Xianmin; Rao, Mahendra S

2016-08-01

We have recently described manufacturing of human induced pluripotent stem cells (iPSC) master cell banks (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Reports, 5(4), 647-659, 2015). In this manuscript, we describe the detailed characterization of the two iPSC clones generated using this process, including whole genome sequencing (WGS), microarray, and comparative genomic hybridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibration material and with a reporter subclone and lines made by a similar process from different donors. We believe that iPSCs are likely to be used to make multiple clinical products. We further believe that the lines used as input material will be used at different sites and, given their immortal status, will be used for many years or even decades. Therefore, it will be important to develop assays to monitor the state of the cells and their drift in culture. We suggest that a detailed characterization of the initial status of the cells, a comparison with some calibration material and the development of reporter sublcones will help determine which set of tests will be most useful in monitoring the cells and establishing criteria for discarding a line.

A Newly Defined and Xeno-Free Culture Medium Supports Every-Other-Day Medium Replacement in the Generation and Long-Term Cultivation of Human Pluripotent Stem Cells.

PubMed

Ahmadian Baghbaderani, Behnam; Tian, Xinghui; Scotty Cadet, Jean; Shah, Kevan; Walde, Amy; Tran, Huan; Kovarcik, Don Paul; Clarke, Diana; Fellner, Thomas

2016-01-01

Human pluripotent stem cells (hPSCs) present an unprecedented opportunity to advance human health by offering an alternative and renewable cell resource for cellular therapeutics and regenerative medicine. The present demand for high quality hPSCs for use in both research and clinical studies underscores the need to develop technologies that will simplify the cultivation process and control variability. Here we describe the development of a robust, defined and xeno-free hPSC medium that supports reliable propagation of hPSCs and generation of human induced pluripotent stem cells (hiPSCs) from multiple somatic cell types; long-term serial subculturing of hPSCs with every-other-day (EOD) medium replacement; and banking fully characterized hPSCs. The hPSCs cultured in this medium for over 40 passages are genetically stable, retain high expression levels of the pluripotency markers TRA-1-60, TRA-1-81, Oct-3/4 and SSEA-4, and readily differentiate into ectoderm, mesoderm and endoderm. Importantly, the medium plays an integral role in establishing a cGMP-compliant process for the manufacturing of hiPSCs that can be used for generation of clinically relevant cell types for cell replacement therapy applications.

Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells

PubMed Central

2012-01-01

Background The bone morphogenetic proteins (BMPs) belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs) and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST) cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs) and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP) stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. Results We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p53. Conclusion We propose that rhBMP-2 has great therapeutic potential in bone marrow cells by serving as a tumor suppressor to increase p53 and the pro-apoptotic proteins Bad and Bax, as well as by increasing the activity of phosphorylated caspase 3. Study design Canine bone marrow mesenchymal stem cells associated with rhBMP2 in canine osteosarcoma treatment: "in vitro" study PMID:22356869

Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells.

PubMed

Rici, Rose Eli Grassi; Alcântara, Dayane; Fratini, Paula; Wenceslau, Cristiane Valverde; Ambrósio, Carlos Eduardo; Miglino, Maria Angelica; Maria, Durvanei Augusto

2012-02-22

The bone morphogenetic proteins (BMPs) belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs) and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST) cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs) and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP) stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p53. We propose that rhBMP-2 has great therapeutic potential in bone marrow cells by serving as a tumor suppressor to increase p53 and the pro-apoptotic proteins Bad and Bax, as well as by increasing the activity of phosphorylated caspase 3. Canine bone marrow mesenchymal stem cells associated with rhBMP2 in canine osteosarcoma treatment: "in vitro" study.

The Royan Public Umbilical Cord Blood Bank: Does It Cover All Ethnic Groups in Iran Based on HLA Diversity?

PubMed

Ebrahimkhani, Saeideh; Farjadian, Shirin; Ebrahimi, Marzieh

2014-04-01

Umbilical cord blood (UCB) stem cells allow the transplantation of partially human leukocyte antigen (HLA)-matched grafts and are a valuable resource for the treatment of hematologic malignancies and heritable hematologic, immunologic and metabolic diseases, especially when a compatible bone marrow donor is unavailable. The aim of this study was to determine how many ethnic groups in Iran are covered by the available UCB units based on HLA diversity. From 2009 until mid-2013, 4,981 (30.3%) of the 16,437 UCB samples collected met the storage criteria and were cryopreserved at a public cord blood bank (CBB) in Tehran, Iran. HLA-A, -B and -DRB1 were typed in 1,793 samples. The mean volume of the cryopreserved samples was 81.25 ± 20.3 ml. The range of total nucleated cells per unit was 51 × 10(7)-107 × 10(7). The most common HLA alleles were HLA-A*2 (17%) and HLA-A*24 (15.6%), HLA-B*35 (16.8%) and HLA-B*51 (13.9%), and HLA-DRB1*11 (20%) and HLA-DRB1*15 (14%). The predominant haplotypes were HLA-A*24-B*35-DRB1*11 (2%), HLA-A*02-B*50-DR*07 (1.8%), and HLA-A*02-B*51-DRB1*11 (1.5%). Based on the HLA-DRB1 profiles, the UCB units available at the Royan public UCB bank are a potentially adequate resource for hematopoietic stem cell transplantation for Iranian recipients belonging to particular ethnic groups. Regular educational programs to improve the public knowledge of UCB for transplantation can enhance the public CBB stocks for all Iranian ethnic groups in the future.

Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics.

PubMed

Jimenez, Antonio; Fung, Henry C; Christopherson, Kent W

2011-11-01

The field of hematopoietic stem cell transplantation (HSCT) has overcome many obstacles that have led to our current clinical ability to utilize cells collected from marrow, mobilized peripheral blood, or umbilical cord blood for the treatment of malignant and nonmalignant hematologic diseases. It is in this context that it becomes evident that future progress will lie in our development of an understanding of the biology by which the process of HSCT is regulated. By understanding the cellular components and the mechanisms by which HSCT is either enhanced or suppressed it will then be possible to design therapeutic strategies to improve rates of engraftment that will have a positive impact on immune reconstitution post-HSCT. In this review we focus primarily on allogeneic hematopoietic stem cell transplantation (allo-HSCT), the current challenges associated with allo-HSCT, and some developing strategies to improve engraftment in this setting. © 2011 American Association of Blood Banks.

Optimizing the method for generation of integration-free induced pluripotent stem cells from human peripheral blood.

PubMed

Gu, Haihui; Huang, Xia; Xu, Jing; Song, Lili; Liu, Shuping; Zhang, Xiao-Bing; Yuan, Weiping; Li, Yanxin

2018-06-15

Generation of induced pluripotent stem cells (iPSCs) from human peripheral blood provides a convenient and low-invasive way to obtain patient-specific iPSCs. The episomal vector is one of the best approaches for reprogramming somatic cells to pluripotent status because of its simplicity and affordability. However, the efficiency of episomal vector reprogramming of adult peripheral blood cells is relatively low compared with cord blood and bone marrow cells. In the present study, integration-free human iPSCs derived from peripheral blood were established via episomal technology. We optimized mononuclear cell isolation and cultivation, episomal vector promoters, and a combination of transcriptional factors to improve reprogramming efficiency. Here, we improved the generation efficiency of integration-free iPSCs from human peripheral blood mononuclear cells by optimizing the method of isolating mononuclear cells from peripheral blood, by modifying the integration of culture medium, and by adjusting the duration of culture time and the combination of different episomal vectors. With this optimized protocol, a valuable asset for banking patient-specific iPSCs has been established.

Determining Sediment Sources in the Anacostia River Watershed

NASA Astrophysics Data System (ADS)

Devereux, O. H.; Needelman, B. A.; Prestegaard, K. L.; Gellis, A. C.; Ritchie, J. C.

2005-12-01

Suspended sediment is a water-quality problem in the Chesapeake Bay. This project is designed to identify sediment sources in an urban watershed, the Northeast Branch of the Anacostia River (in Washington, D.C. and Maryland - drainage area = 188.5 km2), which delivers sediment directly to the Bay. This watershed spans two physiographic regions - the Piedmont and Coastal Plain. Bank sediment and suspended-sediment deposits were characterized using the following techniques: radionuclide (Cs-137) analysis by gamma ray spectrometry, trace-element analysis by ICP-MS, clay mineralogy by XRD, and particle-size analysis by use of a laser particle-size analyzer. Sampling of bank and suspended sediment was designed to: a) characterize tributary inputs from both Piedmont and Coastal Plain sources, and b) differentiate tributary inputs from bank erosion along the main stem of the Northeast Branch. Thirteen sample sites were chosen that represent tributary source areas of each physiographic region and the main stem where mixing occurs. Surface samples of the banks were compared to overbank deposits from a ten year storm (a proxy for the suspended sediments). Fingerprint components are selected from these data. Cesium-137 concentrations were analyzed for bank and overbank deposits for each physiographic region. No clear differences were seen between the two physiographic regions. Significant differences were observed between upland tributaries and the main stem of the Anacostia River. The average activity of Cs-137 for the tributaries was 5.4 bq/kg and the average for the main stem was 1.1 bq/kg. This suggests that there is significant erosion and storage of sediment in the tributaries. The low activity from Cs-137 in the main stem suggests a lack of storage of sediment along the main stem of the river. For the trace-element data, we focused on elements that showed significant variation among the sites. For the bank sediment, these elements include: Sr, V, Y, Ce, and Nd. For the overbank deposits, Zr, V, Ba, Ce, and Cu showed significant variability. In both physiographic regions, Pb is primarily found in bank deposits, while Cu is found in higher concentrations in overbank deposits. The Cs-137 data clearly showed the erosion and storage of sediment patterns in the watershed. The trace-element data indicate that stream banks may be differentiated from overbank deposits.

Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

PubMed Central

Pascale, Natascha; La Russa, Raffaele; Liso, Arcangelo; Salerno, Monica

2017-01-01

Allogenic hematopoietic progenitor cell transplantation (allo-HSCT) is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA-) identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient's risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved. PMID:28680446

Umbilical cord blood: Current status & promise for the future

PubMed Central

McKenna, David; Sheth, Jayesh

2011-01-01

Umbilical cord blood (UCB) has been shown to be a suitable source of haematopoietic stem cells (HSCs) for haematopoietic reconstitution. An increase in the number of UCB transplants indicates an expansion of utility in a broad spectrum of disease conditions. Along with the advantages, UCB also has limitations, and hence several investigators are working to further optimize UCB for this use. Beyond haematopoietic transplantation, additional potential applications of UCB include immunotherapy, tissue engineering and regenerative medicine. UCB banking has improved with time largely due to involvement of professional organizations and their published standards. However, accreditation of these organizations remains voluntary, and in India three of ten banks are public with the remaining being private. Only one public and one private bank are American Association of Blood Banks (AABB) accredited in India. Government agencies need to provide regulatory and safety oversight, which is lacking in serveral countries. Public policy regarding UCB is in its infancy throughout most of the world. Ethical issues, including access to UCB banking and use as therapy for diseases other than haematological and metabolic disorders are in the early phase of trials and remain speculative. PMID:21985808

Cord blood banking - bio-objects on the borderlands between community and immunity.

PubMed

Brown, Nik; Williams, Rosalind

2015-01-01

Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.

Cord blood collection and banking from a population with highly diverse geographic origins increase HLA diversity in the registry and do not lower the proportion of validated cord blood units: experience of the Marseille Cord Blood Bank.

PubMed

Bordoni, C; Magalon, J; Gilbertas, C; Gamerre, M; Le Coz, P; Berthomieu, M; Chabannon, C; Di Cristofaro, J; Picard, C

2015-04-01

Several Cord Blood (CB) Bank studies suggested that ethnicity impaired CB unit (CBU) qualification. The Bone Marrow Donors Worldwide registries present an over-representation of unrelated donors (UD) from Northwestern European descent. This raises the question of equality of access to hematopoietic stem cells transplant, especially in the Mediterranean zone, which has taken in many waves of immigration. The aim of our study is to address whether, in the Marseille CB Bank, CBU qualification rate is impaired by geographic origin. The study compared biological characteristics of 106 CBU disqualified for total nucleated cell (TNC) count (dCBU) and 136 qualified CBU in relation to registry enrichment and haplotype origin. A high proportion (>80%) of both dCBU and CBU had at least one non-European haplotype and enrich CB and UD registries to a higher extent than those with two European haplotypes (P<0.001). No difference was observed between TNC count and volume according to geographic origin. Our study shows that diverse Mediterranean origins do not have an impact on the CBU qualification rate. Partnership with Mediterranean birth clinics with highly trained staff is a reasonable option to increase the HLA diversity of CB Bank inventories and to improve the representation of minorities.

Storage and qualification of viable intact human amniotic graft and technology transfer to a tissue bank.

PubMed

Laurent, Romain; Nallet, Aurélie; Obert, Laurent; Nicod, Laurence; Gindraux, Florelle

2014-06-01

Human amniotic membrane (hAM) is known to have good potential to help the regeneration of tissue. It has been used for over 100 years in many medical disciplines because of its properties, namely a scaffold containing stem cells and growth factors, with low immunogenicity and anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. In order to use this "boosted membrane" as an advanced therapeutic medicinal product for bone repair, we aimed to observe the influence of tissue culture and/or cryopreservation on cell viability and tissue structure, and secondly, to adapt to a tissue bank, identify easy processes to store hAM containing viable cells and to verify the quality of the graft before its release for use. To this end, we tested different published culture or cryopreservation storage conditions and cell viability assays. Tissue structure was evaluated by Giemsa staining and was compared to histological analysis. Preliminary results show no dramatic decrease in cell viability in cultured hAM as compared to cryopreserved hAM, but tissue structure alterations were observed with both storage conditions. Histological and immunohistochemical data highlight that tissue damage was associated with significantly modified protein expression, which could lead to a possible loss of differentiation potential. Finally, we report that trypan blue and Giemsa staining could constitute controls that are "materially and easily transferable" to a tissue bank.

The tissue banking in cancer and stem cell research.

PubMed

Graziano, Antonio; Biunno, Ida; De Blasio, Pasquale; Giordano, Antonio

2007-08-01

The Sapio Award was established in 1999 by the Sapio Group along with several Italian universities and research centers to recognize Italian scientists who have made a major contribution to the discovery or development of novel technologies in the fields of biotechnology, social and health services, nonotechnology and biosecurity in agricultural production and scientific distribution. The 2006 edition of the award meeting centered around the issues of tissue banks and biorepositories and translational medicine. The organizing committee divided this edition into a pre-meeting held in Milan on October 18, 2006 and a master meeting on October 19, 2006, held at the ISS in Rome. A summary of these meetings is given.

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

PubMed

Lund, Raymond D; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lu, Bin; Girman, Sergej; Bischoff, N; Sauvé, Yves; Lanza, Robert

2006-01-01

Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.

Ethical, moral, and theological insights into advances in male pediatric and adolescent fertility preservation.

PubMed

Ramstein, J J; Halpern, J; Gadzinski, A J; Brannigan, R E; Smith, J F

2017-07-01

The successful treatment of boys with cancer has led to increasing attention to preserving their quality of life after completing cancer therapy. One of the top priorities for living a full life is keeping open the opportunity to have children. While sperm banking for males facing sterilizing cancer treatment can be effective, this approach requires subsequent use of reproductive procedures such as in vitro fertilization (IVF) or intrauterine insemination (IUI) to achieve a pregnancy. Advances in fertility preservation techniques may allow pre-pubertal boys to conceive using advanced stem cell technologies and stem cell transplantation in the future. This review summarizes the ethical positions of leading medical societies and explores the religious and moral stances of major religious institutions regarding these options. © 2017 American Society of Andrology and European Academy of Andrology.

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks.

PubMed

Magalon, Jeremy; Maiers, Martin; Kurtzberg, Joanne; Navarrete, Cristina; Rubinstein, Pablo; Brown, Colin; Schramm, Catherine; Larghero, Jérome; Katsahian, Sandrine; Chabannon, Christian; Picard, Christophe; Platz, Alexander; Schmidt, Alexander; Katz, Gregory

2015-01-01

Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies. Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit. When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long term. We also found that using a pre-freezing level of 18 x 10(8) TNC would be the most cost-effective strategy for a public bank. Our study shows that a swift transition from strategy A to C can play a vital role in preventing public cord blood banks worldwide from collapsing.

Geotechnical Implications for the use of Alfalfa in Experimental Studies of Alluvial-Channel Morphology and Planform

NASA Astrophysics Data System (ADS)

Pollen, N.; Simon, A.

2006-12-01

Research on the interactions between vegetation and channel flow dynamics has shown that vegetation is an important control on river morphology and planform. Increased vegetation density is commonly linked to a decrease in bank erosion and lateral migration rates. Roots add to bank strength through the production of a reinforced soil-root matrix, and vegetation can also act to increase bank stability through its hydrological effects, including canopy interception, and removal of soil water through evapotranspiration. Flow dynamics are also affected by vegetation, with a number of studies showing a linkage between vegetation density and width- depth-velocity relations and bank roughness. To evaluate the effects of vegetation on channel morphology and planform, several experimental studies in flumes have used alfalfa sprouts (Medicago sativa) to seed the bed and banks of experimental channels. In such studies, the effects of vegetation are accounted for by qualitatively increasing the resistance of the bank material to lateral erosion. However, the material properties of alfalfa roots and stems, and the actual increase in resistance provided to the banks under different densities of alfalfa have thus far been ignored. To quantify this added erosion resistance, alfalfa sprouts were grown for 7 to 21 days, in sand with a d50 of 0.23 mm. At regular intervals, roots and stems were tested to measure tensile strength and forces required for pullout. Results of the tensile-strength measurements display the typical non-linear decrease of tensile strength (in MPa) with increasing root diameter but the curve is shifted to the left (weaker for a given diameter) of other riparian species. However, to calculate the increase in bank cohesion due to alfalfa roots, it is necessary to also account for the number of roots, and the distribution of different root diameters. The number of roots was calculated for a range of stem densities (0 to 10 stems/cm2), assuming a single, un-branching root per stem. Values for the additional cohesion provided by the alfalfa roots were calculated using the root- reinforcement model, RipRoot, producing values of 0 to 11.8 kPa. These results provide a means of quantifying the additional bank resistance provided to experimental channels under different stem/root densities. Cohesion values obtained in this way were successfully related to studies of braiding intensity published by others. The geometric properties of alfalfa scale up from experiments in flumes to approximate young trees on a floodplain. However, soil properties such as cohesion cannot be scaled. As such, the cohesion values due to roots calculated here represent the actual magnitude of reinforcement provided, rather than a scaled value.

Characterisation of insulin-producing cells differentiated from tonsil derived mesenchymal stem cells.

PubMed

Kim, So-Yeon; Kim, Ye-Ryung; Park, Woo-Jae; Kim, Han Su; Jung, Sung-Chul; Woo, So-Youn; Jo, Inho; Ryu, Kyung-Ha; Park, Joo-Won

2015-01-01

Tonsil-derived (T-) mesenchymal stem cells (MSCs) display mutilineage differentiation potential and self-renewal capacity and have potential as a banking source. Diabetes mellitus is a prevalent disease in modern society, and the transplantation of pancreatic progenitor cells or various stem cell-derived insulin-secreting cells has been suggested as a novel therapy for diabetes. The potential of T-MSCs to trans-differentiate into pancreatic progenitor cells or insulin-secreting cells has not yet been investigated. We examined the potential of human T-MSCs to trans-differentiate into pancreatic islet cells using two different methods based on β-mercaptoethanol and insulin-transferin-selenium, respectively. First, we compared the efficacy of the two methods for inducing differentiation into insulin-producing cells. We demonstrated that the insulin-transferin-selenium method is more efficient for inducing differentiation into insulin-secreting cells regardless of the source of the MSCs. Second, we compared the differentiation potential of two different MSC types: T-MSCs and adipose-derived MSCs (A-MSCs). T-MSCs had a differentiation capacity similar to that of A-MSCs and were capable of secreting insulin in response to glucose concentration. Islet-like clusters differentiated from T-MSCs had lower synaptotagmin-3, -5, -7, and -8 levels, and consequently lower secreted insulin levels than cells differentiated from A-MSCs. These results imply that T-MSCs can differentiate into functional pancreatic islet-like cells and could provide a novel, alternative cell therapy for diabetes mellitus. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Advanced Good Cell Culture Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems.

PubMed

Pamies, David; Bal-Price, Anna; Chesné, Christophe; Coecke, Sandra; Dinnyes, Andras; Eskes, Chantra; Grillari, Regina; Gstraunthaler, Gerhard; Hartung, Thomas; Jennings, Paul; Leist, Marcel; Martin, Ulrich; Passier, Robert; Schwamborn, Jens C; Stacey, Glyn N; Ellinger-Ziegelbauer, Heidrun; Daneshian, Mardas

2018-04-13

A major reason for the current reproducibility crisis in the life sciences is the poor implementation of quality control measures and reporting standards. Improvement is needed, especially regarding increasingly complex in vitro methods. Good Cell Culture Practice (GCCP) was an effort from 1996 to 2005 to develop such minimum quality standards also applicable in academia. This paper summarizes recent key developments in in vitro cell culture and addresses the issues resulting for GCCP, e.g. the development of induced pluripotent stem cells (iPSCs) and gene-edited cells. It further deals with human stem-cell-derived models and bioengineering of organo-typic cell cultures, including organoids, organ-on-chip and human-on-chip approaches. Commercial vendors and cell banks have made human primary cells more widely available over the last decade, increasing their use, but also requiring specific guidance as to GCCP. The characterization of cell culture systems including high-content imaging and high-throughput measurement technologies increasingly combined with more complex cell and tissue cultures represent a further challenge for GCCP. The increasing use of gene editing techniques to generate and modify in vitro culture models also requires discussion of its impact on GCCP. International (often varying) legislations and market forces originating from the commercialization of cell and tissue products and technologies are further impacting on the need for the use of GCCP. This report summarizes the recommendations of the second of two workshops, held in Germany in December 2015, aiming map the challenge and organize the process or developing a revised GCCP 2.0.

Transplantation of stem cells from human exfoliated deciduous teeth for bone regeneration in the dog mandibular defect

PubMed Central

Behnia, Ali; Haghighat, Abbas; Talebi, Ardeshir; Nourbakhsh, Nosrat; Heidari, Fariba

2014-01-01

AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth (SHED) transplanted for bone regeneration in the dog mandibular defect. METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-and-through defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level. RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue (P = 0.248), woven bone (P = 0.248) and compact bone (P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period. CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs. PMID:25258673

Invasive Australian Acacia seed banks: Size and relationship with stem diameter in the presence of gall-forming biological control agents.

PubMed

Strydom, Matthys; Veldtman, Ruan; Ngwenya, Mzabalazo Z; Esler, Karen J

2017-01-01

Australian Acacia are invasive in many parts of the world. Despite significant mechanical and biological efforts to control their invasion and spread, soil-stored seed banks prevent their effective and sustained removal. In response South Africa has had a strong focus on employing seed reducing biological control agents to deal with Australian Acacia invasion, a programme that is considered as being successful. To provide a predictive understanding for their management, seed banks of four invasive Australian acacia species (Acacia longifolia, A. mearnsii, A. pycnantha and A. saligna) were studied in the Western Cape of South Africa. Across six to seven sites for each species, seed bank sizes were estimated from dense, monospecific stands by collecting 30 litter and soil samples. Average estimated seed bank size was large (1017 to 17261 seed m-2) as was annual input into the seed bank, suggesting that these seed banks are not residual but are replenished in size annually. A clear relationship between seed bank size and stem diameter was established indicating that mechanical clearing should be conducted shortly after fire-stimulated recruitment events or within old populations when seed banks are small. In dense, monospecific stands seed-feeding biological control agents are not effective in reducing seed bank size.

A novel procedure to improve functional preservation of hematopoietic stem and progenitor cells in cord blood stored at +4°c before cryopreservation.

PubMed

Chevaleyre, Jean; Rodriguez, Laura; Duchez, Pascale; Plainfossé, Marie; Dazey, Bernard; Lapostolle, Véronique; Vlaski, Marija; Brunet de la Grange, Philippe; Delorme, Bruno; Ivanovic, Zoran

2014-08-01

During storage and transportation of collected cord blood units (CBUs) to the bank prior to their processing and cryopreservation, it is imperative to preserve the functional capacities of a relatively small amount of cells of interest (stem and progenitor cells) which are critical for graft potency. To improve CBU storage efficiency, we conceived an approach based on the following two principles: (1) to provide a better nutritive and biochemical environment to stem and progenitor cells in CB and (2) to prevent the hyperoxygenation of these cells transferred from a low- (1.1%-4% O2 in the CB) to a high-oxygen (20%-21% O2 in atmosphere) concentration. Our hypothesis is confirmed by the functional assessment of stem cell (hematopoietic reconstitution capacity in immunodeficient mice-scid repopulating cell assay) and committed progenitor activities (capacity of in vitro colony formation and of ex vivo expansion) after the storage period with our medium (HP02) in gas-impermeable bags. This storage procedure maintains the full functional capacity of a CBU graft for 3 days with respect to day 0. Further, using this procedure, a graft stored 3 days at +4°C exhibits better functional capacities than one currently used in routine storage (CBUs stored at +4°C for 1 day in gas-permeable bags and without medium). We provided the proof of principle of our approach, developed a clinical-scale kit and performed a preclinical assay demonstrating the feasibility and efficiency of our CBU preservation protocol through all steps of preparation (volume reduction, freezing, and thawing).

Regenerative medicine in India: trends and challenges in innovation and regulation.

PubMed

Tiwari, Shashank S; Raman, Sujatha; Martin, Paul

2017-10-01

The government of India has heavily promoted research and development in regenerative medicine together with domestic innovation and business development initiatives. Together, these promise a revolution in healthcare and public empowerment in India. Several national and transnational linkages have emerged to develop innovative capacity, most prominently in stem cell and cord blood banking, as well as in gene therapy, tissue engineering, biomaterials and 3D printing. However, challenges remain of achieving regulatory oversight, viable outputs and equitable impacts. Governance of private cord blood banking, nanomaterials and 3D bioprinting requires more attention. A robust social contract is also needed in healthcare more generally, so that participation in research and innovation in regenerative medicine is backed up by treatments widely accessible to all.

Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair.

PubMed

Li, Yueying; Liu, Tie; Van Halm-Lutterodt, Nicholas; Chen, JiaYu; Su, Qingjun; Hai, Yong

2016-02-17

An attempt was made to reprogram peripheral blood cells into human induced pluripotent stem cell (hiPSCs) as a new cell source for cartilage repair. We generated chondrogenic lineage from human peripheral blood via hiPSCs using an integration-free method. Peripheral blood cells were either obtained from a human blood bank or freshly collected from volunteers. After transforming peripheral blood cells into iPSCs, the newly derived iPSCs were further characterized through karyotype analysis, pluripotency gene expression and cell differentiation ability. iPSCs were differentiated through multiple steps, including embryoid body formation, hiPSC-mesenchymal stem cell (MSC)-like cell expansion, and chondrogenic induction for 21 days. Chondrocyte phenotype was then assessed by morphological, histological and biochemical analysis, as well as the chondrogenic expression. hiPSCs derived from peripheral blood cells were successfully generated, and were characterized by fluorescent immunostaining of pluripotent markers and teratoma formation in vivo. Flow cytometric analysis showed that MSC markers CD73 and CD105 were present in monolayer cultured hiPSC-MSC-like cells. Both alcian blue and toluidine blue staining of hiPSC-MSC-chondrogenic pellets showed as positive. Immunohistochemistry of collagen II and X staining of the pellets were also positive. The sulfated glycosaminoglycan content was significantly increased, and the expression levels of the chondrogenic markers COL2, COL10, COL9 and AGGRECAN were significantly higher in chondrogenic pellets than in undifferentiated cells. These results indicated that peripheral blood cells could be a potential source for differentiation into chondrogenic lineage in vitro via generation of mesenchymal progenitor cells. This study supports the potential applications of utilizing peripheral blood cells in generating seed cells for cartilage regenerative medicine in a patient-specific and cost-effective approach.

Endogenous, very small embryonic-like stem cells: critical review, therapeutic potential and a look ahead.

PubMed

Bhartiya, Deepa; Shaikh, Ambreen; Anand, Sandhya; Patel, Hiren; Kapoor, Sona; Sriraman, Kalpana; Parte, Seema; Unni, Sreepoorna

2016-12-01

Both pluripotent very small embryonic-like stem cells (VSELs) and induced pluripotent stem (iPS) cells were reported in 2006. In 2012, a Nobel Prize was awarded for iPS technology whereas even today the very existence of VSELs is not well accepted. The underlying reason is that VSELs exist in low numbers, remain dormant under homeostatic conditions, are very small in size and do not pellet down at 250-280g. The VSELs maintain life-long tissue homeostasis, serve as a backup pool for adult stem cells and are mobilized under stress conditions. An imbalance in VSELs function (uncontrolled proliferation) may result in cancer. The electronic database 'Medline/Pubmed' was systematically searched with the subject heading term 'very small embryonic-like stem cells'. The most primitive stem cells that undergo asymmetric cell divisions to self-renew and give rise to progenitors still remain elusive in the hematopoietic system and testes, while the presence of stem cells in ovary is still being debated. We propose to review the available literature on VSELs, the methods of their isolation and characterization, their ontogeny, how they compare with embryonic stem (ES) cells, primordial germ cells (PGCs) and iPS cells, and their role in maintaining tissue homeostasis. The review includes a look ahead on how VSELs will result in paradigm shifts in basic reproductive biology. Adult tissue-specific stem cells including hematopoietic, spermatogonial, ovarian and mesenchymal stem cells have good proliferation potential and are indeed committed progenitors (with cytoplasmic OCT-4), which arise by asymmetric cell divisions of pluripotent VSELs (with nuclear OCT-4). VSELs are the most primitive stem cells and postulated to be an overlapping population with the PGCs. Rather than migrating only to the gonads, PGCs migrate and survive in various adult body organs throughout life as VSELs. VSELs express both pluripotent and PGC-specific markers and are epigenetically and developmentally more mature compared with ES cells obtained from the inner cell mass of a blastocyst-stage embryo. As a result, VSELs readily differentiate into three embryonic germ layers and spontaneously give rise to both sperm and oocytes in vitro. Like PGCs, VSELs do not divide readily in culture, nor produce teratoma or integrate in the developing embryo. But this property of being relatively quiescent allows endogenous VSELs to survive various kinds of toxic insults. VSELs that survive oncotherapy can be targeted to induce endogenous regeneration of non-functional gonads. Transplanting healthy niche (mesenchymal) cells have resulted in improved gonadal function and live births. Being quiescent, VSELs possibly do not accumulate genomic (nuclear or mitochondrial) mutations and thus may be ideal endogenous, pluripotent stem cell candidates for regenerative and reproductive medicine. The presence of VSELs in adult gonads and the fact that they survive oncotherapy may obviate the need to bank gonadal tissue for fertility preservation prior to oncotherapy. VSELs and their ability to undergo spermatogenesis/neo-oogenesis in the presence of a healthy niche will help identify newer strategies toward fertility restoration in cancer survivors, delaying menopause and also enabling aged mothers to have better quality eggs. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Derivation of the King's College London human embryonic stem cell lines.

PubMed

Stephenson, Emma L; Braude, Peter R

2010-04-01

Since the derivation of the first human embryonic stem cell (hESC) line in 1998, there has been substantial interest in the potential of these cells for regenerative medicine and cell therapy and in the use of hESCs carrying clinically relevant genetic mutations as models for disease research and therapeutic target identification. There is still a need to improve derivation efficiency and further the understanding of the basic biology of these cells and to develop clinical grade culture systems with the aim of producing cell lines suitable for subsequent manipulation for therapy. The derivation of initial hESC lines at King's College London is discussed here, with focus on derivation methodology. Each of the derivations was distinctive. Although the stage and morphology of each blastocyst were generally similar in each attempt, the behaviour of the colonies was unpredictable; colony morphology and development was different with each attempt. Days 5, 6 and 7 blastocysts were used successfully, and the number of days until appearance of stem-like cells varied from 4 to 14 d. Routine characterisation analyses were performed on three lines, all of which displayed appropriate marker expression and survived cryopreservation-thaw cycles. From the lines discussed, four are at various stages of the deposition process with the UKSCB, one is pending submission and two are unsuitable for banking. Continued open and transparent reporting of results and collaborations will maximise the efficiency of derivation and facilitate the development of standardised protocols for the derivation and early culture of hESC lines.

Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord: immunophenotypic characterization and differentiation potential

PubMed Central

2014-01-01

Introduction Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identical in vitro conditions, to compare these sources for research or an allogeneic therapy cell bank. Methods The BM-MSCs, AT-MSCs and UC-MSCs were cultured and evaluated in vitro for their osteogenic, adipogenic and chondrogenic differentiation potential. Additionally, MSCs were assessed for CD105, CD44, CD34, CD90 and MHC-II markers by flow cytometry, and MHC-II was also assessed by immunocytochemistry. To interpret the flow cytometry results, statistical analysis was performed using ANOVA. Results The harvesting and culturing procedures of BM-MSCs, AT-MSCs and UC-MSCs were feasible, with an average cell growth until the third passage of 25 days for BM-MSCs, 15 days for AT-MSCs and 26 days for UC-MSCs. MSCs from all sources were able to differentiate into osteogenic (after 10 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs), adipogenic (after 8 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs) and chondrogenic (after 21 days for BM-MSCs, AT-MSCs and UC-MSCs) lineages. MSCs showed high expression of CD105, CD44 and CD90 and low or negative expression of CD34 and MHC-II. The MHC-II was not detected by immunocytochemistry techniques in any of the MSCs studied. Conclusions The BM, AT and UC are feasible sources for harvesting equine MSCs, and their immunophenotypic and multipotency characteristics attained minimal criteria for defining MSCs. Due to the low expression of MHC-II by MSCs, all of the sources could be used in clinical trials involving allogeneic therapy in horses. However, the BM-MSCs and AT-MSCs showed fastest ‘‘in vitro’’ differentiation and AT-MSCs showed highest cell growth until third passage. These findings suggest that BM and AT may be preferable for cell banking purposes. PMID:24559797

Effectiveness and cost analysis of "just-in-time" salvage plerixafor administration in autologous transplant patients with poor stem cell mobilization kinetics.

PubMed

Li, Jie; Hamilton, Ellie; Vaughn, Louette; Graiser, Michael; Renfroe, Heather; Lechowicz, Mary Jo; Langston, Amelia; Prichard, Jefferson Mark; Anderson, Darlene; Gleason, Charise; Lonial, Sagar; Flowers, Christopher R; Kaufman, Jonathan L; Waller, Edmund K

2011-10-01

Plerixafor is a recently Food and Drug Administration (FDA)-approved CXCR4 antagonist, which is combined with granulocyte-colony-stimulating factor (G-CSF) to facilitate stem cell mobilization of lymphoma and myeloma patients. To evaluate the effectiveness and the related costs of a "just-in-time" strategy of plerixafor administration, we performed a retrospective cohort study comparing 148 consecutive lymphoma and myeloma patients in whom mobilization was attempted during 2008 before the Food and Drug Administration (FDA) approval of plerixafor with 188 consecutive patients mobilized during 2009 after FDA approval. Plerixafor was administered to 64 of 188 patients considered to be at risk for mobilization failure due to either their medical history ("high risk," n = 23) or the occurrence of peripheral blood CD34+ count of fewer than 15 × 10(6) cells/L with a white blood cell count of greater than 10 × 10(9) cells/L after at least 5 days of G-CSF administration (just-in-time, n = 41). The success rates of collecting a minimum transplant CD34+ cell dose (≥2 × 10(6) cells/kg) or target cell dose (≥5 × 10(6) lymphoma or ≥10 × 10(6) CD34+ cells/kg myeloma) in the just-in-time patients compared favorably with the 36 poor mobilizers collected with G-CSF alone: 93% versus 72% and 42% versus 22%, respectively. The use of plerixafor in selected high-risk patients and poor mobilizers did not increase the total charges associated with stem cell collection when compared with poor mobilizers treated with G-CSF alone. The targeted use of plerixafor increased the overall success rate of mobilizing a minimum number of CD34+ cells from 93% to 98% in patients with hematologic malignancies scheduled for autotransplant and increased the overall charges associated with stem cell collection in all patients by an average of 17%. © 2011 American Association of Blood Banks.

Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

NASA Astrophysics Data System (ADS)

Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia.

PubMed

Crompton, Kylie E; Elwood, Ngaire; Kirkland, Mark; Clark, Pamela; Novak, Iona; Reddihough, Dinah

2014-07-01

Umbilical cord blood may have therapeutic benefit in children with cerebral palsy (CP), but further studies are required. On first appearance it seems that Australia is well placed for such a trial because we have excellence in CP research backed by extensive CP registers, and both public and private cord blood banks. We aimed to examine the possibilities of conducting a trial of autologous umbilical cord blood cells (UCBCs) as a treatment for children with CP in Australia. Data linkages between CP registers and cord blood banks were used to estimate potential participant numbers for a trial of autologous UCBCs for children with CP. As of early 2013, one Victorian child with CP had cord blood stored in the public bank, and between 1 and 3 children had their cord blood stored at Cell Care Australia (private cord blood bank). In New South Wales, we counted two children on the CP register who had their stored cord blood available in early 2013. We estimate that there are between 10 and 24 children with CP of any type who have autologous cord blood available across Australia. In nations with small populations like Australia, combined with Australia's relatively low per capita cord blood storage to date, it is not currently feasible to conduct trials of autologous UCBCs for children with CP. Other options must be explored, such as allogeneic UCBCs or prospective trials for neonates at risk of CP. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Cryopreservation of hematopoietic stem and progenitor cells amplified ex vivo from cord blood CD34+ cells.

PubMed

Duchez, Pascale; Chevaleyre, Jean; Brunet de la Grange, Philippe; Vlaski, Marija; Boiron, Jean-Michel; Wouters, Guy; Ivanovic, Zoran

2013-09-01

Our ex vivo expansion procedure starting from cord blood (CB) CD34+ cells enabled expansion of committed progenitors (CPs) without a negative impact on hematopoietic stem cells (HSCs) exhibiting both short- and long-term repopulating capacity. Upgraded to clinical scale (Macopharma HP01 in the presence of stem cell factor, FLT3-L [100 ng/mL each], granulocyte-colony-stimulating factor [10 ng/mL], and thrombopoietin [20 ng/mL]), it is being used for an ongoing clinical trial (adult allogeneic context) yielding promising preliminary results. Transplantation of ex vivo expanded CB cells is becoming a reality, while the issue of expanded cells' cryopreservation emerges as an option that allows the conservation of the product for transportation and future use. Here, we investigated whether it is possible to maintain the functional HSC and CP properties after freezing and thawing of expanded cells. We compared cryopreservation efficiency of the ex vivo expanded CB cells using the standard protocol (freezing solution human serum albumin (HSA)-dimethyl sulfoxide [DMSO]) with the newly designed protocol based on an enriched freezing solution (HP01-DMSO) with respect to the viability index, number of CD34+ and total cells, and recovery of CPs (colony-forming units) and HSCs (NOG/Scid/gamma-null mice engraftment). Cryopreservation and thawing of expanded CB cells using the "standard" procedure (HSA-DMSO) reduced recovery of the CPs (40%) and HSCs (drastically decreasing engraftment capacity). HP01-based protocol resulted in improvement of preservation of both CPs (>60%) and HSCs (nonaltered engraftment capacities). Functional maintenance of the expanded graft by cryopreservation is feasible in conditions compatible with human cell therapy requirements. © 2012 American Association of Blood Banks.

Thrombopoietin to replace megakaryocyte-derived growth factor: impact on stem and progenitor cells during ex vivo expansion of CD34+ cells mobilized in peripheral blood.

PubMed

Duchez, Pascale; Chevaleyre, Jean; Vlaski, Marija; Dazey, Bernard; Bijou, Fontanet; Lafarge, Xavier; Milpied, Noël; Boiron, Jean-Michel; Ivanovic, Zoran

2011-02-01

The first protocol of ex vivo expansion that enabled almost total abrogation of postmyeloablative chemotherapy neutropenia was based on a three-cytokine cocktail (stem cell factor [SCF], granulocyte-colony-stimulating factor [G-CSF], pegylated-megakaryocyte growth and development factor [PEG-MGDF]) in a serum-free medium. Since the clinical-grade molecule MGDF is no longer available on the market, we evaluated its substitution by thrombopoietin (TPO). CD34+ cells of myeloma patients were expanded for 10 days in serum-free cultures with SCF, G-CSF, or MGDF (100 ng/mL) or with TPO (2.5, 10, 20, 50, and 100 ng/mL) instead of MGDF. Day 10 amplifications of total nucleated cells, CD34+ cells, committed progenitors (CFCs), the capacity of engraftment of NOD/SCID mice (SCID repopulating cells [SRCs]), and the immunophenotype of cells in expansion product (CD13, CD14, CD33, CD41, CD61) were analyzed. TPO in doses of 2.5 and 10 ng/mL exhibits an effect comparable to that of MGDF (100 ng/mL) on total, CD34+, and CFCs amplification. Compared to MGDF, TPO (starting at 10 ng/mL) enhances two- to threefold the percentage of megakaryocyte lineage cells (CD41+ and CD61+). Finally, TPO maintains or even enhances (depending on dose) SRC activity. The use of TPO instead of MGDF in our protocol is feasible without any negative effect on progenitor cell expansion. Furthermore, applied in dose of 10 or 100 ng/mL it could enhance both the stem cell activity and the percentage of megakaryocyte lineage cells in expansion product. © 2010 American Association of Blood Banks.

Ethical issues in umbilical cord blood banking. Working Group on Ethical Issues in Umbilical Cord Blood Banking.

PubMed

Sugarman, J; Kaalund, V; Kodish, E; Marshall, M F; Reisner, E G; Wilfond, B S; Wolpe, P R

1997-09-17

Banking umbilical cord blood (UCB) to be used as a source of stem cells for transplantation is associated with a set of ethical issues. An examination of these issues is needed to inform public policy and to raise the awareness of prospective parents, clinicians, and investigators. Individuals with expertise in anthropology, blood banking, bone marrow transplantation, ethics, law, obstetrics, pediatrics, and the social sciences were invited to join the Working Group on Ethical Issues in Umbilical Cord Blood Banking. Members were assigned topics to present to the Working Group. Following independent reviews, background materials were sent to the Working Group. Individual presentations of topics at a 2-day meeting were followed by extensive group discussions in which consensus emerged. A writing committee then drafted a document that was circulated to the entire Working Group. After 3 rounds of comments over several months, all but 1 member of the Working Group agreed with the presentation of our conclusions. (1) Umbilical cord blood technology is promising although it has several investigational aspects; (2) during this investigational phase, secure linkage should be maintained of stored UCB to the identity of the donor; (3) UCB banking for autologous use is associated with even greater uncertainty than banking for allogeneic use; (4) marketing practices for UCB banking in the private sector need close attention; (5) more data are needed to ensure that recruitment for banking and use of UCB are equitable; and (6) the process of obtaining informed consent for collection of UCB should begin before labor and delivery.

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks

PubMed Central

Magalon, Jeremy; Maiers, Martin; Kurtzberg, Joanne; Navarrete, Cristina; Rubinstein, Pablo; Brown, Colin; Schramm, Catherine; Larghero, Jérome; Katsahian, Sandrine; Chabannon, Christian; Picard, Christophe; Platz, Alexander; Schmidt, Alexander; Katz, Gregory

2015-01-01

Background Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies. Methods Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit. Results When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long term. We also found that using a pre-freezing level of 18 x 108 TNC would be the most cost-effective strategy for a public bank. Conclusion Our study shows that a swift transition from strategy A to C can play a vital role in preventing public cord blood banks worldwide from collapsing. PMID:26624279

What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us about Transplant Immunogenetics

PubMed Central

La Nasa, Giorgio; Vacca, Adriana; Littera, Roberto; Piras, Eugenia; Orru, Sandro; Greco, Marianna; Carcassi, Carlo; Caocci, Giovanni

2016-01-01

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS) and thalassemia-free survival (TFS) rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD) remains the most important complication in unrelated HSCT in thalassemia, leading to significant rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individualize appropriate strategies for its prevention and management. This review provides an overview of recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia. PMID:27872728

Breast Milk Enhances Growth of Enteroids: An Ex Vivo Model of Cell Proliferation.

PubMed

Lanik, Wyatt E; Xu, Lily; Luke, Cliff J; Hu, Elise Z; Agrawal, Pranjal; Liu, Victoria S; Kumar, Rajesh; Bolock, Alexa M; Ma, Congrong; Good, Misty

2018-02-15

Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to establish human enteroid ex vivo culture systems are important to model intestinal pathophysiology and to study the particular cellular responses involved. In recent years, enteroids from mice and humans are being cultured, passaged, and banked away for future use in several laboratories across the world. This enteroid platform can be used to test the effects of various treatments and drugs and what effects are exerted on different cell types in the intestine. Here, a protocol for establishing primary stem cell-derived small intestinal enteroids derived from neonatal mice and premature human intestine is provided. Moreover, this enteroid culture system was utilized to test the effects of species-specific breast milk. Mouse breast milk can be obtained efficiently using a modified human breast pump and expressed mouse milk can then be used for further research experiments. We now demonstrate the effects of expressed mouse, human, and donor breast milk on the growth and proliferation of enteroids derived from neonatal mice or premature human small intestine.

Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regulatory T cells and reduces graft versus host disease.

PubMed

Fan, Xiubo; Gay, Florence Pik Hoon; Ong, Shin-Yeu; Ang, Justina May Lynn; Chu, Pat Pak Yan; Bari, Sudipto; Lim, Tony Kiat Hon; Hwang, William Ying Khee

2013-05-01

Double cord blood transplantation (DCBT) may shorten neutrophil and platelet recovery times compared with standard umbilical cord blood transplantation. However, DCBT may be associated with a higher incidence of graft versus host disease (GVHD). In this study, we explored the effect of ex vivo expansion of a single cord blood unit (CBU) in a DCBT setting on GVHD and engraftment. Post-thaw cryopreserved CBUs from cord blood banks, hereinafter termed "banked" CBUs, were co-cultured with confluent bone marrow mesenchymal stromal cells (MSCs) supplemented with a cytokine cocktail comprising 100 ng/mL stem cell factor, 50 ng/mL flt3-ligand, 100 ng/mL thrombopoietin and 20 ng/mL insulin-like growth factor binding protein 2 for 12 days. When DCBT of one unexpanded and one expanded CBU was performed in non-obese diabetic/severe combined immunodeficient-IL2Rgamma(null) (NOD/SCID-IL2γ(-/-), NSG) mice, the expanded CBU significantly boosted in vivo hematopoiesis of the unexpanded CBU. The median survival of NSG mice was significantly improved from 63.4% (range, 60.0-66.7%) for mice receiving only unexpanded units to 86.5% (range, 80.0-92.9%) for mice receiving an expanded unit (P < 0.001). The difference in survival appeared to be due to a lower incidence of GVHD in the mice receiving expanded cells. This effect on GVHD was mediated by a significant increase in regulatory T cells seen in the presence of MSC co-culture. MSC-supported ex vivo expansion of "banked" CBU boosted unexpanded CBU hematopoiesis in vivo, increased regulatory T cell content and decreased the incidence of GVHD. Copyright © 2013. Published by Elsevier Inc.

Vascular Smooth Muscle Cells From Hypertensive Patient-Derived Induced Pluripotent Stem Cells to Advance Hypertension Pharmacogenomics.

PubMed

Biel, Nikolett M; Santostefano, Katherine E; DiVita, Bayli B; El Rouby, Nihal; Carrasquilla, Santiago D; Simmons, Chelsey; Nakanishi, Mahito; Cooper-DeHoff, Rhonda M; Johnson, Julie A; Terada, Naohiro

2015-12-01

Studies in hypertension (HTN) pharmacogenomics seek to identify genetic sources of variable antihypertensive drug response. Genetic association studies have detected single-nucleotide polymorphisms (SNPs) that link to drug responses; however, to understand mechanisms underlying how genetic traits alter drug responses, a biological interface is needed. Patient-derived induced pluripotent stem cells (iPSCs) provide a potential source for studying otherwise inaccessible tissues that may be important to antihypertensive drug response. The present study established multiple iPSC lines from an HTN pharmacogenomics cohort. We demonstrated that established HTN iPSCs can robustly and reproducibly differentiate into functional vascular smooth muscle cells (VSMCs), a cell type most relevant to vasculature tone control. Moreover, a sensitive traction force microscopy assay demonstrated that iPSC-derived VSMCs show a quantitative contractile response on physiological stimulus of endothelin-1. Furthermore, the inflammatory chemokine tumor necrosis factor α induced a typical VSMC response in iPSC-derived VSMCs. These studies pave the way for a large research initiative to decode biological significance of identified SNPs in hypertension pharmacogenomics. Treatment of hypertension remains suboptimal, and a pharmacogenomics approach seeks to identify genetic biomarkers that could be used to guide treatment decisions; however, it is important to understand the biological underpinnings of genetic associations. Mouse models do not accurately recapitulate individual patient responses based on their genetics, and hypertension-relevant cells are difficult to obtain from patients. Induced pluripotent stem cell (iPSC) technology provides a great interface to bring patient cells with their genomic data into the laboratory and to study hypertensive responses. As an initial step, the present study established an iPSC bank from patients with primary hypertension and demonstrated an effective and reproducible method of generating functional vascular smooth muscle cells. ©AlphaMed Press.

DMSO‐ and Serum‐Free Cryopreservation of Wharton's Jelly Tissue Isolated From Human Umbilical Cord

PubMed Central

Shivakumar, Sharath Belame; Bharti, Dinesh; Subbarao, Raghavendra Baregundi; Jang, Si‐Jung; Park, Ji‐Sung; Ullah, Imran; Park, Ji‐Kwon; Byun, June‐Ho

2016-01-01

ABSTRACT The facile nature of mesenchymal stem cell (MSC) acquisition in relatively large numbers has made Wharton's jelly (WJ) tissue an alternative source of MSCs for regenerative medicine. However, freezing of such tissue using dimethyl sulfoxide (DMSO) for future use impedes its clinical utility. In this study, we compared the effect of two different cryoprotectants (DMSO and cocktail solution) on post‐thaw cell behavior upon freezing of WJ tissue following two different freezing protocols (Conventional [−1°C/min] and programmed). The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO. Post‐thaw growth characteristics and stem cell behavior of Wharton's jelly mesenchymal stem cells (WJMSCs) from WJ tissue cryopreserved with a cocktail solution in conjunction with programmed method (Prog‐Cock) were comparable with WJMSCs from fresh WJ tissue. They preserved their expression of surface markers, pluripotent factors, and successfully differentiated in vitro into osteocytes, adipocytes, chondrocytes, and hepatocytes. They also produced lesser annexin‐V‐positive cells compared to cells from WJ tissue stored using cocktail solution in conjunction with the conventional method (Conv‐Cock). Real‐time PCR and Western blot analysis of post‐thaw WJMSCs from Conv‐Cock group showed significantly increased expression of pro‐apoptotic factors (BAX, p53, and p21) and reduced expression of anti‐apoptotic factor (BCL2) compared to WJMSCs from the fresh and Prog‐Cock group. Therefore, we conclude that freezing of fresh WJ tissue using cocktail solution in conjunction with programmed freezing method allows for an efficient WJ tissue banking for future MSC‐based regenerative therapies. J. Cell. Biochem. 117: 2397–2412, 2016. © 2016 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc. PMID:27038129

Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women

PubMed Central

Screnci, Maria; Murgi, Emilia; Pirrè, Guglielma; Valente, Elisabetta; Gesuiti, Paola; Corona, Francesca; Girelli, Gabriella

2012-01-01

Background. Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women. Materials and methods. This study was conducted at the “Sapienza” University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women. Results. Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use. Discussion. The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions. PMID:22507856

Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women.

PubMed

Screnci, Maria; Murgi, Emilia; Pirrè, Guglielma; Valente, Elisabetta; Gesuiti, Paola; Corona, Francesca; Girelli, Gabriella

2012-07-01

Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women. This study was conducted at the "Sapienza" University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women. Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use. The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions.

Awareness of cord blood collection and the impact on banking.

PubMed

Bhandari, Rusha; Lindley, Amy; Bhatla, Deepika; Babic, Aleksandar; Mueckl, Kathy; Rao, Rakesh; Brooks, Paula; Geiler, Vicki; Gross, Gilad; Al-Hosni, Mohamad; Shenoy, Shalini

2017-07-01

Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation especially in minority populations with limited chances of finding a histocompatible volunteer donor in the registry. UCB has the advantages of early availability, successful outcomes despite some histocompatibility mismatch, and low incidence of chronic graft-versus-host disease. Public cord blood banks that disseminate UCB products for transplant depend on voluntary donation at participating hospitals and obstetrical providers for collection. Using survey questionnaires, we evaluated attitudes toward UCB donation, the frequency of donation, and provider opinions on UCB collection in the greater St. Louis metropolitan area that caters to minority ethnicities in significant numbers. Our data suggest that nervousness and lack of information regarding the donation and utility of the product were ubiquitous reasons for not donating. Additionally, irrespective of age or level of education, women relied on healthcare providers for information regarding UCB donation. Providers reported primarily time constraints to discussing UCB donation at prenatal visits (54%). Of the interviewees, 62% donated UCB. Fallout due to refusal or preferring private banking was miniscule. These results suggest that dedicated personnel focused on disseminating information, obtaining consent, and collecting the UCB product at major hospitals can enrich cord blood banks especially with minority cords. Sustained and focused efforts could improve upon a relatively high wastage rate and ensure a robust supply of UCB products at local public banks. © 2017 Wiley Periodicals, Inc.

Cord blood banking activities at a university hospital in northeast Mexico: an 8-year experience.

PubMed

Jaime-Perez, Jose C; Monreal-Robles, Roberto; Colunga-Pedraza, Julia; Mancías-Guerra, Consuelo; Rodríguez-Romo, Laura; Gómez-Almaguer, David

2012-12-01

Umbilical cord blood (UCB) represents an alternative source of stem cells for transplantation for the treatment of hematologic malignancies and genetic disorders. There is scarce information detailing cord blood bank (CBB) collection and transplantation activities from developing countries. We documented our experience at a public university hospital in northeast Mexico. We carried out a retrospective and descriptive analysis of our CBB activity during an 8-year period from May 2002 to September 2010. Collection, processing, and cryopreservation of CB were carried out following standard operating procedures. The minimum volume and total nucleated cell (TNC) content for cryopreservation were 80 mL and 8.0 × 10(8) , respectively. A total of 1256 UCB units were collected; 428 (34%) were banked and 828 (66%) were discarded. The main reason for exclusion was biologic: low volume and/or low number of TNC accounted for 84% of the total discarded units. Cryopreserved cord blood units (CBUs) had a median volume of 113.8 mL (range, 80-213.2 mL) and 13.0 × 10(8) (range, 8 × 10(8) -36.6 × 10(8) ) TNCs. Cell viability was 99.3% (88-100%). The median CD34+ cell content was 4.0 × 10(6) (0.46 × 10(6) -19.38 × 10(6) ). Sixteen units have been released for transplantation, leading to a utilization rate of 3.7%. CBB demands considerable human and financial resources; it is then essential for centers at developing countries to share their experience, results, and databases to increase the probability of finding matching units for their patients. Efforts to create and maintain CBBs allow to offer this therapeutic option at an affordable cost. © 2012 American Association of Blood Banks.

Avian germplasm preservation: embryonic stem cells or primordial germ cells?

PubMed

Petitte, J N

2006-02-01

Presently, avian genetic resources are best maintained as living collections of birds. Unfortunately, these stocks have been under constant pressure to be destroyed because of the decline in the number of Poultry Science Departments and pressures to cut costs at land grant institutions. Cryopreservation of semen is often suggested as a means to bank avian germplasm. However, this is only applicable for single-gene traits and does not allow for full reconstitution of the genetics of the original line. Over the last 15 yr, advances in the manipulation of the early chick embryo, manipulation of primordial germ cells (PGC), and the culture of embryonic stem cells (ESC) suggests that cryopreservation of blastodermal cells, ESC, or PGC might offer a means to preserve the entire genome of highly selected, specialized stocks of poultry. Freezing each of these cell types is possible with varying degrees of efficiency. Similarly, the effectiveness of generating germ line chimeras using blastodermal cells, ESC, or PGC also varies greatly. Other factors that must be considered include the choice of the recipient lines to develop the germ line chimeras and the number of individuals needed to reconstitute the line. Finally, the low efficiency rate of reconstitution and the high cost associated with current technologies makes these approaches prohibitive. Significant challenges remain to be overcome before the entire genome of poultry stocks can be routinely cryoperserved and reconstituted.

Magnetic induction heating of superparamagnetic nanoparticles during rewarming augments the recovery of hUCM-MSCs cryopreserved by vitrification.

PubMed

Wang, Jianye; Zhao, Gang; Zhang, Zhengliang; Xu, Xiaoliang; He, Xiaoming

2016-03-01

Cryopreservation by vitrification has been recognized as a promising strategy for long-term banking of living cells. However, the difficulty to generate a fast enough heating rate to minimize devitrification and recrystallization-induced intracellular ice formation during rewarming is one of the major obstacles to successful vitrification. We propose to overcome this hurdle by utilizing magnetic induction heating (MIH) of magnetic nanoparticles to enhance rewarming. In this study, superparamagnetic (SPM) Fe3O4 nanoparticles were synthesized by a chemical coprecipitation method. We successfully applied the MIH of Fe3O4 nanoparticles for rewarming human umbilical cord matrix mesenchymal stem cells (hUCM-MSCs) cryopreserved by vitrification. Our results show that extracellular Fe3O4 nanoparticles with MIH may efficiently suppress devitrification and/or recrystallization during rewarming and significantly improve the survival of vitrified cells. We further optimized the concentration of Fe3O4 nanoparticles and the current of an alternating current (AC) magnetic field for generating the MIH to maximize cell viability. Our results indicate that MIH in an AC magnetic field with 0.05% (w/v) Fe3O4 nanoparticles significantly facilitates rewarming and improves the cryopreservation outcome of hUCM-MSCs by vitrification. The application of MIH of SPM nanoparticles to achieve rapid and spatially homogeneous heating is a promising strategy for enhanced cryopreservation of stem cells by vitrification. Here we report the successful synthesis and application of Fe3O4 nanoparticles for magnetic induction heating (MIH) to enhance rewarming of vitrification-cryopreserved human umbilical cord matrix mesenchymal stem cells (hUCM-MSCs). We found that MIH-enhanced rewarming greatly improves the survival of vitrification-cryopreserved hUCM-MSCs. Moreover, the hUCM-MSCs retain their intact stemness and multilineage potential of differentiation post cryopreservation by vitrification with the MIH-enhanced rewarming. Therefore, the novel MIH-enhanced cell vitrification is valuable to facilitate the long-term storage of hUCM-MSCs and possibly many other important cells to meet their ever-increasing demand by the burgeoning cell-based medicine. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

PubMed Central

Tompkins, Joshua D.; Jung, Marc; Chen, Chang-yi; Lin, Ziguang; Ye, Jingjing; Godatha, Swetha; Lizhar, Elizabeth; Wu, Xiwei; Hsu, David; Couture, Larry A.; Riggs, Arthur D.

2016-01-01

The directed differentiation of human cardiomyocytes (CMs) from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors. PMID:26981572

Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

PubMed

Abbasalizadeh, Saeed; Baharvand, Hossein

2013-12-01

Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

Ethical issues relating the the banking of umbilical cord blood in Mexico.

PubMed

Serrano-Delgado, V Moises; Novello-Garza, Barbara; Valdez-Martinez, Edith

2009-08-14

Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico. A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord. Conflicts between moral principles and economic interests (non-moral principles) cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks' performance.

Ethical issues relating to the banking of umbilical cord blood in Mexico

PubMed Central

2009-01-01

Background Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico. Discussion A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord. Summary Conflicts between moral principles and economic interests (non-moral principles) cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks' performance. PMID:19678958

Human leukocyte antigen-A, -B, and -DRB1 haplotypes of cord blood units in the Tzu Chi Taiwan Cord Blood Bank.

PubMed

Wen, Shu-Hui; Lai, Meng-Jiun; Yang, Kuo-Liang

2008-07-01

Cord blood (CB) is considered an alternative resource to bone marrow and peripheral blood stem cells (PBSC) for allogeneic stem cell transplantation. In this study, human leukocyte antigen (HLA)-A, -B, and -DRB1 high-resolution allele types were analyzed from a total of 710 CB units in the Tzu Chi Taiwan Cord Blood Bank. We observed 21 HLA-A alleles, 59 HLA-B alleles, and 28 HLA-DRB1 alleles, whereas 19 unique alleles were present in the CB units of 2,023 individuals selected for confirmatory testing in the Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). The allelic associations between the HLA-A and -B locus were stronger than that of either the HLA-B and -DRB1 loci or the HLA-A and -DRB1 loci. The most common haplotype of CB units in the general Taiwanese population was A*3303-B*5801-DRB1*0301 (6.59%), followed by A*0207-B*4601-DRB1*0901 (3.47%) and then A*1101-B*4001-DRB1*0901 (2.11%). Moreover, two haplotypes, A*2402-B*5201-DRB1*1502 and A*0201-B*1301-DRB1*1202, existed uniquely in the CB units but were not observed in the data of TCTMDR. Although the number of CB units studied for high-resolution of HLA typing in the current study is small, we believe our data should provide useful information to increase the chances of obtaining acceptable HLA-A-, -B-, and -DRB1-matched CB units for patients.

Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation.

PubMed

Tzannou, Ifigeneia; Papadopoulou, Anastasia; Naik, Swati; Leung, Kathryn; Martinez, Caridad A; Ramos, Carlos A; Carrum, George; Sasa, Ghadir; Lulla, Premal; Watanabe, Ayumi; Kuvalekar, Manik; Gee, Adrian P; Wu, Meng-Fen; Liu, Hao; Grilley, Bambi J; Krance, Robert A; Gottschalk, Stephen; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E; Leen, Ann M; Omer, Bilal

2017-11-01

Purpose Improvement of cure rates for patients treated with allogeneic hematopoietic stem-cell transplantation (HSCT) will require efforts to decrease treatment-related mortality from severe viral infections. Adoptively transferred virus-specific T cells (VSTs) generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available off-the-shelf product. Patient and Methods We generated a bank of VSTs that recognized five common viral pathogens: Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). The VSTs were administered to 38 patients with 45 infections in a phase II clinical trial. Results A single infusion produced a cumulative complete or partial response rate of 92% (95% CI, 78.1% to 98.3%) overall and the following rates by virus: 100% for BKV (n = 16), 94% for CMV (n = 17), 71% for AdV (n = 7), 100% for EBV (n = 2), and 67% for HHV-6 (n = 3). Clinical benefit was achieved in 31 patients treated for one infection and in seven patients treated for multiple coincident infections. Thirteen of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6. Infusions were safe, and only two occurrences of de novo graft-versus host disease (grade 1) were observed. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks. Conclusion The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product. Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.

Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

PubMed Central

Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

2016-01-01

Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

Zinc accumulation in plant species indigenous to a Portuguese polluted site: relation with soil contamination.

PubMed

Marques, Ana P G C; Rangel, António O S S; Castro, Paula M L

2007-01-01

The levels of zinc accumulated by roots, stems, and leaves of two plant species, Rubus ulmifolius and Phragmites australis, indigenous to the banks of a stream in a Portuguese contaminated site were investigated in field conditions. R. ulmifolius, a plant for which studies on phytoremediation potential are scarce, dominated on the right side of the stream, while P. australis proliferated on the other bank. Heterogeneous Zn concentrations were found along the banks of the stream. Zn accumulation in both species occurred mainly in the roots, with poor translocation to the aboveground sections. R. ulmifolius presented Zn levels in the roots ranging from 142 to 563 mg kg(-1), in the stems from 35 to 110 mg kg(-1), and in the leaves from 45 to 91 mg kg(-1), vs. average soil total Zn concentrations varying from 526 to 957 mg kg(-1). P. australis showed Zn concentrations in the roots from 39 to 130 mg kg(-1), in the stems from 31 to 63 mg kg(-1), and in the leaves from 37 to 83 mg kg(-1), for the lower average soil total Zn levels of 138 to 452 mg kg(-1) found on the banks where they proliferated. Positive correlations were found between the soil total, available and extractable Zn fractions, and metal accumulation in the roots and leaves of R. ulmifolius and in the roots and stems of P. australis. The use of R. ulmifolius and P. australis for phytoextraction purposes does not appear as an effective method of metal removing, but these native metal tolerant plant species may be used to reduce the effects of soil contamination, avoiding further Zn transfer to other environmental compartments.

Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study

PubMed Central

Gratwohl, Alois; Baldomero, Helen; Gratwohl, Michael; Aljurf, Mahmoud; Bouzas, Luis Fernando; Horowitz, Mary; Kodera, Yoshihisa; Lipton, Jeff; Iida, Minako; Pasquini, Marcelo C.; Passweg, Jakob; Szer, Jeff; Madrigal, Alejandro; Frauendorfer, Karl; Niederwieser, Dietger

2013-01-01

Fifty-five years after publication of the first hematopoietic stem cell transplantation this technique has become an accepted treatment option for defined hematologic and non-hematologic disorders. There is considerable interest in understanding differences in its use and trends on a global level and the macro-economic factors associated with these differences. Data on the numbers of hematopoietic stem cell transplants performed in the 3-year period 2006–2008 were obtained from Worldwide Network for Blood and Marrow Transplantation member registries and from transplant centers in countries without registries. Population and macro-economic data were collected from the World Bank and from the International Monetary Fund. Transplant rates were analyzed by indication, donor type, country, and World Health Organization regional offices areas and related to selected health care indicators using single and multiple linear regression analyses. Data from a total of 146,808 patients were reported by 1,411 teams from 72 countries over five continents. The annual number of transplants increased worldwide with the highest relative increase in the Asia Pacific region. Transplant rates increased preferentially in high income countries (P=0.02), not in low or medium income countries. Allogeneic transplants increased for myelodysplasia, chronic lymphocytic leukemia, acute leukemias, and non-malignant diseases but decreased for chronic myelogenous leukemia. Autologous transplants increased for autoimmune and lymphoproliferative diseases but decreased for leukemias and solid tumors. Transplant rates (P<0.01), donor type (P<0.01) aand disease indications (P<0.01) differed significantly between countries and regions. Transplant rates were associated with Gross National Income/capita (P<0.01) but showed a wide variation of explanatory content by donor type, disease indication and World Health Organization region. Hematopoietic stem cell transplantation activity is increasing worldwide. The preferential increase in high income countries, the widening gap between low and high income countries and the significant regional differences suggest that different strategies are required in individual countries to foster hematopoietic stem cell transplantation as an efficient and cost-effective treatment modality. PMID:23508009

Bank accretion and the development of vegetated depositional surfaces along modified alluvial channels

USGS Publications Warehouse

Hupp, C.R.; Simon, A.

1991-01-01

This paper describes the recovery of stable bank form and development of vegetated depositional surfaces along the banks of channelized West Tennessee streams. Most perennial streams in West Tennessee were straightened and dredged since the turn of the century. Patterns of fluvial ecological responses to channelization have previously been described by a six-stage model. Dendrogeomorphic (tree-ring) techniques allowed the determination of location, timing, amount, and rate of bank-sediment deposition. Channel cross sections and ecological analyses made at 101 locations along 12 streams, encompassing bends and straight reaches, show that channel and bank processes initially react vertically to channelization through downcutting. A depositional surface forms on banks once bed-degradation and heightened bank mass wasting processes have eased or slowed. The formation of this depositional surface marks the beginning of bank recovery from channelization. Dominating lateral processes, characteristic of stable or natural channels, return during the formation and expansion of the depositional surface, suggesting a relation with thalweg deflection, point-bar development, and meanderloop extension. Characteristic woody riparian vegetation begins to grow as this depositional surface develops and becomes part of the process and form of restabilizing banks. The depositional surface initially forms low on the bank and tends to maintain a slope of about 24??. Mean accretion rates ranges from 5.9 cm/yr on inside bends to 0 cm/yr on most outside bends; straight reaches have a mean-accretion rate of 4.2 cm/yr. The relatively stable, convex upward, depositional surface expands and ultimately attaches to the flood plain. The time required for the recovery process to reach equilibrium averaged about 50 years. Indicative pioneer speccies of woody riparian vegetation include black willow, river birch, silver maple, and boxelder. Stem densities generally decrease with time after and initial flush of about 160 stems per 100 m2. Together bank accretion and vegetative regrowth appear to be the most important environmental processes involved in channel bank recovery from channelization or rejuvenation. ?? 1991.

Legal and ethical issues in safe blood transfusion.

PubMed

Chandrashekar, Shivaram; Kantharaj, Ambuja

2014-09-01

Legal issues play a vital role in providing a framework for the Indian blood transfusion service (BTS), while ethical issues pave the way for quality. Despite licensing of all blood banks, failure to revamp the Drugs and Cosmetic Act (D and C Act) is impeding quality. Newer techniques like chemiluminescence or nucleic acid testing (NAT) find no mention in the D and C Act. Specialised products like pooled platelet concentrates or modified whole blood, therapeutic procedures like erythropheresis, plasma exchange, stem cell collection and processing technologies like leukoreduction and irradiation are not a part of the D and C Act. A highly fragmented BTS comprising of over 2500 blood banks, coupled with a slow and tedious process of dual licensing (state and centre) is a hindrance to smooth functioning of blood banks. Small size of blood banks compromises blood safety. New blood banks are opened in India by hospitals to meet requirements of insurance providers or by medical colleges as this a Medical Council of India (MCI) requirement. Hospital based blood banks opt for replacement donation as they are barred by law from holding camps. Demand for fresh blood, lack of components, and lack of guidelines for safe transfusion leads to continued abuse of blood. Differential pricing of blood components is difficult to explain scientifically or ethically. Accreditation of blood banks along with establishment of regional testing centres could pave the way to blood safety. National Aids Control Organisation (NACO) and National Blood Transfusion Council (NBTC) deserve a more proactive role in the licensing process. The Food and Drug Administration (FDA) needs to clarify that procedures or tests meant for enhancement of blood safety are not illegal.

Legal and ethical issues in safe blood transfusion

PubMed Central

Chandrashekar, Shivaram; Kantharaj, Ambuja

2014-01-01

Legal issues play a vital role in providing a framework for the Indian blood transfusion service (BTS), while ethical issues pave the way for quality. Despite licensing of all blood banks, failure to revamp the Drugs and Cosmetic Act (D and C Act) is impeding quality. Newer techniques like chemiluminescence or nucleic acid testing (NAT) find no mention in the D and C Act. Specialised products like pooled platelet concentrates or modified whole blood, therapeutic procedures like erythropheresis, plasma exchange, stem cell collection and processing technologies like leukoreduction and irradiation are not a part of the D and C Act. A highly fragmented BTS comprising of over 2500 blood banks, coupled with a slow and tedious process of dual licensing (state and centre) is a hindrance to smooth functioning of blood banks. Small size of blood banks compromises blood safety. New blood banks are opened in India by hospitals to meet requirements of insurance providers or by medical colleges as this a Medical Council of India (MCI) requirement. Hospital based blood banks opt for replacement donation as they are barred by law from holding camps. Demand for fresh blood, lack of components, and lack of guidelines for safe transfusion leads to continued abuse of blood. Differential pricing of blood components is difficult to explain scientifically or ethically. Accreditation of blood banks along with establishment of regional testing centres could pave the way to blood safety. National Aids Control Organisation (NACO) and National Blood Transfusion Council (NBTC) deserve a more proactive role in the licensing process. The Food and Drug Administration (FDA) needs to clarify that procedures or tests meant for enhancement of blood safety are not illegal. PMID:25535417

Using RNA-Seq for gene identification, polymorphism detection and transcript profiling in two alfalfa genotypes with divergent cell wall composition in stems

PubMed Central

2011-01-01

Background Alfalfa, [Medicago sativa (L.) sativa], a widely-grown perennial forage has potential for development as a cellulosic ethanol feedstock. However, the genomics of alfalfa, a non-model species, is still in its infancy. The recent advent of RNA-Seq, a massively parallel sequencing method for transcriptome analysis, provides an opportunity to expand the identification of alfalfa genes and polymorphisms, and conduct in-depth transcript profiling. Results Cell walls in stems of alfalfa genotype 708 have higher cellulose and lower lignin concentrations compared to cell walls in stems of genotype 773. Using the Illumina GA-II platform, a total of 198,861,304 expression sequence tags (ESTs, 76 bp in length) were generated from cDNA libraries derived from elongating stem (ES) and post-elongation stem (PES) internodes of 708 and 773. In addition, 341,984 ESTs were generated from ES and PES internodes of genotype 773 using the GS FLX Titanium platform. The first alfalfa (Medicago sativa) gene index (MSGI 1.0) was assembled using the Sanger ESTs available from GenBank, the GS FLX Titanium EST sequences, and the de novo assembled Illumina sequences. MSGI 1.0 contains 124,025 unique sequences including 22,729 tentative consensus sequences (TCs), 22,315 singletons and 78,981 pseudo-singletons. We identified a total of 1,294 simple sequence repeats (SSR) among the sequences in MSGI 1.0. In addition, a total of 10,826 single nucleotide polymorphisms (SNPs) were predicted between the two genotypes. Out of 55 SNPs randomly selected for experimental validation, 47 (85%) were polymorphic between the two genotypes. We also identified numerous allelic variations within each genotype. Digital gene expression analysis identified numerous candidate genes that may play a role in stem development as well as candidate genes that may contribute to the differences in cell wall composition in stems of the two genotypes. Conclusions Our results demonstrate that RNA-Seq can be successfully used for gene identification, polymorphism detection and transcript profiling in alfalfa, a non-model, allogamous, autotetraploid species. The alfalfa gene index assembled in this study, and the SNPs, SSRs and candidate genes identified can be used to improve alfalfa as a forage crop and cellulosic feedstock. PMID:21504589

Derivation of Xeno-Free and GMP-Grade Human Embryonic Stem Cells – Platforms for Future Clinical Applications

PubMed Central

Aizenman, Einat; Kirshberg, Sophie; Ilouz, Nili; Gil, Yaniv; Berman-Zaken, Yael; Perlman, Temima Schnitzer; Geva, Nitshia; Levy, Ora; Arbell, Daniel; Simon, Alex; Ben-Meir, Assaf; Shufaro, Yoel; Laufer, Neri; Reubinoff, Benjamin E.

2012-01-01

Clinically compliant human embryonic stem cells (hESCs) should be developed in adherence to ethical standards, without risk of contamination by adventitious agents. Here we developed for the first time animal-component free and good manufacturing practice (GMP)-compliant hESCs. After vendor and raw material qualification, we derived xeno-free, GMP-grade feeders from umbilical cord tissue, and utilized them within a novel, xeno-free hESC culture system. We derived and characterized three hESC lines in adherence to regulations for embryo procurement, and good tissue, manufacturing and laboratory practices. To minimize freezing and thawing, we continuously expanded the lines from initial outgrowths and samples were cryopreserved as early stocks and banks. Batch release criteria included DNA-fingerprinting and HLA-typing for identity, characterization of pluripotency-associated marker expression, proliferation, karyotyping and differentiation in-vitro and in-vivo. These hESCs may be valuable for regenerative therapy. The ethical, scientific and regulatory methodology presented here may serve for development of additional clinical-grade hESCs. PMID:22745653

Wisdom teeth: mankind's future third vice-teeth?

PubMed

Zou, DuoHong; Zhao, Jun; Ding, WangHui; Xia, LunGuo; Jang, XinQuan; Huang, YuanLiang

2010-01-01

The third molar teeth (wisdom teeth) represent the last eruption of the teeth in the human dentition. Throughout evolution, the mandible has had a tendency to decrease in size; the third molar teeth are often impacted, resulting in incomplete tooth eruption that often causes clinical pericoronitis, dental caries, and pericemental abscess. Therefore, the wisdom teeth are often extracted. Moreover, wisdom teeth are often removed for clinical orthodontic treatment. On the other hand, tooth loss due to periodontal disease, dental caries, trauma, or a variety of genetic disorders continues to affect people's lives. Autologous tissues for dental tissue regeneration that could replace lost teeth could provide a vital alternative to currently available clinical treatments. To pursue this goal, we hypothesize that human third molar tooth buds can be obtained during development. Human wisdom tooth germination tissue could then be placed into an embryonic stem cell bank for storage. When the donor's other teeth are missing, embryonic stem cell and tissue engineering technologies, will permit the restoration of the missing teeth. Therefore wisdom teeth will be mankind's future third vice-teeth.

CELLPEDIA: a repository for human cell information for cell studies and differentiation analyses.

PubMed

Hatano, Akiko; Chiba, Hirokazu; Moesa, Harry Amri; Taniguchi, Takeaki; Nagaie, Satoshi; Yamanegi, Koji; Takai-Igarashi, Takako; Tanaka, Hiroshi; Fujibuchi, Wataru

2011-01-01

CELLPEDIA is a repository database for current knowledge about human cells. It contains various types of information, such as cell morphologies, gene expression and literature references. The major role of CELLPEDIA is to provide a digital dictionary of human cells for the biomedical field, including support for the characterization of artificially generated cells in regenerative medicine. CELLPEDIA features (i) its own cell classification scheme, in which whole human cells are classified by their physical locations in addition to conventional taxonomy; and (ii) cell differentiation pathways compiled from biomedical textbooks and journal papers. Currently, human differentiated cells and stem cells are classified into 2260 and 66 cell taxonomy keys, respectively, from which 934 parent-child relationships reported in cell differentiation or transdifferentiation pathways are retrievable. As far as we know, this is the first attempt to develop a digital cell bank to function as a public resource for the accumulation of current knowledge about human cells. The CELLPEDIA homepage is freely accessible except for the data submission pages that require authentication (please send a password request to cell-info@cbrc.jp). Database URL: http://cellpedia.cbrc.jp/

Giving to receive? The right to donate in umbilical cord blood banking for stem cell therapies.

PubMed

Machin, Laura L; Brown, Nik; McLeod, Danae

2012-03-01

To explore the views of lay and professional stakeholders about the donation of cord blood to public banks in England and the policies surrounding it. Qualitative in-depth interviews were undertaken between April 2009 and August 2010 with 62 participants based in England who play a key role in cord blood banking and therapy. All interviews were recorded, transcribed in full, and coded and analysed thematically. Participants claimed pregnant women had a right to know of the value of cord blood. This highlighted the flaws of the existing donation infrastructure, which was portrayed as playing a significant role in determining public health. Participants called for a right to donate cord blood to readdress the inequity in healthcare services for pregnant women and transplant recipients. Donors maintained a sense of right over their donation when they discussed cord blood donation as potentially benefiting their family as well as society. In order to keep receiving donated body parts, tissue and blood, there is a need to take into account the way in which donation operates within a prevalent 'rights' discourse. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Attitudes of Swiss mothers toward unrelated umbilical cord blood banking 6 months after donation.

PubMed

Danzer, Enrico; Holzgreve, Wolfgang; Troeger, Carolyn; Kostka, Ulrike; Steimann, Sabine; Bitzer, Johanes; Gratwohl, Alois; Tichelli, André; Seelmann, Kurt; Surbek, Daniel V

2003-05-01

During the past decade, the use of umbilical cord blood (CB) as a source of transplantable hematopoietic stem cells has been increasing. Little is known about the psychosocial consequences that later affect parents after unrelated CB donation. The objective of this study was to evaluate the attitudes of mothers toward unrelated donation of umbilical CB for transplantation 6 months after giving birth. A prospective study was performed with a standardized, anonymous questionnaire distributed to 131 women 6 months after CB donation. The questionnaire included topics concerning views about the ethical accuracy of having donated CB, emotional responses after donation, concerns about genetic testing and research with CB samples, attitude toward anonymity between her child and possible unrelated CB recipient, and willingness to repeatedly donate umbilical CB in a next pregnancy. The vast majority (96.1%) stated that they would donate umbilical CB again, and all respondents were certain that their decision to have donated umbilical CB was ethical. With regard to the potential risks of genetic testing and "experimentation" of umbilical CB, a significant correlation (p = 0.01) was found between negative attitudes and the decision not to donate umbilical CB again. Additionally, it was observed that women who had a negative experience concerning the donation of CB would not donate again (p = 0.004). This study shows a high degree of satisfaction of unrelated umbilical CB donation for banking in women 6 months after delivery. Despite a well-performed and detailed informed consent procedure, one of the ongoing issues for the donators in CB banking involves the concern regarding of improper use of the cells, such as genetic testing or experimentation. Accurate and detailed counseling of pregnant women and their partners therefore maximizes the likelihood that they will donate CB for unrelated banking. These data provide a basis for the improvement of donor selection procedures and public education regarding the use of CB for banking and transplantation.

Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing.

PubMed

Russom, Diana; Ahmed, Amira; Gonzalez, Nancy; Alvarnas, Joseph; DiGiusto, David

2012-01-01

Regulatory requirements for the manufacturing of cell products for clinical investigation require a significant level of record-keeping, starting early in process development and continuing through to the execution and requisite follow-up of patients on clinical trials. Central to record-keeping is the management of documentation related to patients, raw materials, processes, assays and facilities. To support these requirements, we evaluated several laboratory information management systems (LIMS), including their cost, flexibility, regulatory compliance, ongoing programming requirements and ability to integrate with laboratory equipment. After selecting a system, we performed a pilot study to develop a user-configurable LIMS for our laboratory in support of our pre-clinical and clinical cell-production activities. We report here on the design and utilization of this system to manage accrual with a healthy blood-donor protocol, as well as manufacturing operations for the production of a master cell bank and several patient-specific stem cell products. The system was used successfully to manage blood donor eligibility, recruiting, appointments, billing and serology, and to provide annual accrual reports. Quality management reporting features of the system were used to capture, report and investigate process and equipment deviations that occurred during the production of a master cell bank and patient products. Overall the system has served to support the compliance requirements of process development and phase I/II clinical trial activities for our laboratory and can be easily modified to meet the needs of similar laboratories.

Evaluations of bioantioxidants in cryopreservation of umbilical cord blood using natural cryoprotectants and low concentrations of dimethylsulfoxide.

PubMed

Motta, J P R; Gomes, B E; Bouzas, L F; Paraguassú-Braga, F H; Porto, L C

2010-06-01

Transplantation using hematopoietic stem cells from umbilical cord blood (UCB) is a life-saving treatment option for patients with select oncologic diseases, immunologic diseases, bone marrow failure, and others. Often this transplant modality requires cryopreservation and storage of hematopoietic stem cells (HSC), which need to remain cryopreserved in UCB banks for possible future use. The most widely used cryoprotectant is dimethylsulfoxide (Me(2)SO), but at 37 degrees C, it is toxic to cells and for patients, infusion of cryopreserved HSC with Me(2)SO has been associated with side effects. Freezing of cells leads to chemical change of cellular components, which results in physical disruption. Reactive oxygen species (ROS) generation also has been implicated as cause of damage to cells during freezing. We assessed the ability of two bioantioxidants and two disaccharides, to enhance the cryopreservation of UCB. UCB was processed and subjected to cryopreservation in solutions containing different concentrations of Me(2)SO, bioantioxidants and disaccharides. Samples were thawed, and then analysed by: flow cytometry analysis, CFU assay and MTT viability assay. In this study, our analyses showed that antioxidants, principally catalase, performed greater preservation of: CD34+ cells, CD123+ cells, colony-forming units and cell viability, all post-thawed, compared with the standard solution of cryopreservation. Our present studies show that the addition of catalase improved the cryopreservation outcome. Catalase may act on reducing levels of ROS, further indicating that accumulation of free radicals indeed leads to death in cryopreserved hematopoietic cells. Copyright 2010 Elsevier Inc. All rights reserved.

Family directed umbilical cord blood banking for acute leukemia: usage rate in hematopoietic stem cell transplantation.

PubMed

Screnci, M; Murgi, E; Tamburini, A; Pecci, M R; Ballatore, G; Cusanno, A; Valle, V; Luciani, P; Corona, F; Girelli, G

2015-04-01

Family-directed umbilical cord blood (UCB) collection and banking is indicated in women delivering healthy babies who already have a member of their own family with a disease potentially treatable with an allogeneic hematopoietic stem cell (HSCs) transplantation (HSCT). The rapid availability of UCB is an important issue in HSCs procurement particularly for recipients with acute leukemia who urgently need HSCT. The aims of this study were to assess the usage rate of family UCB collections directed to patients with acute leukemia and to investigate the factors influencing the usage rate. A total of 113 families were enrolled, 118 UCB units were successfully collected and one collection failed due to emergency occurred during delivery. Among these, 7 collections were required for children who were in urgent need of a transplant: three HLA-matched units were successfully transplanted, respectively after 2, 5 and 6 months from collection; three collections resulted HLA-mismatched, while HLA-typing is pending for one unit. The remaining collections were mostly required for potential future use, among these units only one was transplanted in a HLA compatible sibling after 3 years and 4 months from collection. After a median time of storage of 8.5 years (range 0.1-20 years) a total of 4/118 (3.4 %) collection has been transplanted. During this time interval, considering only patients who have had the need of a transplant, the main factor influencing low utilization rate of UCB collections was due to HLA disparity, indeed among typed UCB unit mostly (77 %) resulted HLA mismatched with the intended recipient.

Business on hope: a case study on private cord blood stem cell banking.

PubMed

Kiatpongsan, Sorapop

2008-04-01

Traditionally, medical practice has been recognized as one of the professional practices with high honors. The interaction between physicians and patients is to provide health care services without the profit orientation. In modernized economy and in today's world of business, the relationship between doctors and patients has been dramatically changed. This transformation is very obvious in the private sector. Health care providers sell their services. Patients have been approached as customers. Decisions to make an investment on new medical technologies or new services would accompany with careful consideration on cost-benefit ratio, on marketing and also on short and long term return of the investment. However most of the medical services available in the past were focusing on the "real" and "tangible" products. This means that the patients or the customers would obtain diagnosis, treatment, palliation or prevention for the fees they paid. They can at least obtain and can feel some direct or indirect health benefits from the services. With the advancement of science and technology, there is recently a new model of business that sells only the hope for future use. Private cord blood stem cell banking is a good example for this business model. Actually, business on hope is not the brand new business model. Insurance is a well-known classical prototype of business on hope. However, when this kind of business model is applied for medical services, there should be some precautions and also intervention including an oversight system from the government sector to make sure that all the information delivered to the clients and family is accurate and unbiased. From the public policy perspective, this business of hope should be appropriately regulated to preserve consumer rights while promoting the advancement of science and technology through sustainable business development.

The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells.

PubMed

Wajid, Nadia; Naseem, Rashida; Anwar, Sanam Saiqa; Awan, Sana Javaid; Ali, Muhammad; Javed, Sara; Ali, Fatima

2015-09-01

Stomal cells derived from Wharton's jelly of human umbilical cord (WJMSCs) are considered as the potential therapeutic agents for regeneration and are getting famous for stem cell banking. Our study aims to evaluate the effects of gestational diabetes on proliferation capacity and viability of WJMSCs. Mesenchymal stromal cells were isolated from Wharton's jelly of human umbilical cords from normal and gestational diabetic (DWJMSCs) mothers. Growth patterns of both types of cells were analyzed through MTT assay and population doubling time. Cell survival, cell death and glucose utilization were estimated through trypan blue exclusion assay, LDH assay and glucose detection assay respectively. Angiogenic ability was evaluated by immunocytochemistry and ELISA for VEGF A. Anti-cancerous potential was analyzed on HeLa cells. DWJMSCs exhibited low proliferative rate, increased population doubling time, reduced cell viability and increased cell death. Interestingly, DWJMSCs were found to have a reduced glucose utilization and anti-cancerous ability while enhanced angiogenic ability. Gestational diabetes induces adverse effects on growth, angiogenic and anti-cancerous potential of WJMSCs.

Cost comparative study of autologous peripheral blood progenitor cells (PBPC) and bone marrow (ABM) transplantations for non-Hodgkin's lymphoma patients.

PubMed

Woronoff-Lemsi, M C; Arveux, P; Limat, S; Deconinck, E; Morel, P; Cahn, J Y

1997-12-01

Intensive high-dose chemotherapy with autologous stem-cell support has become a common treatment strategy for non-Hodgkin's lymphomas. A cost-identification analysis was conducted comparing 10 patients autografted with PBSC to 10 others autografted with BM. The analysis included harvest and graft until graft day +100 and was carried out from the point of view of the hospital setting. Resources used, logistic and direct medical costs per patient were identified, and sensitivity analyses performed. The cost distribution was different. Stem cell harvest was more expensive for PBPC ($9030) and BM ($4745); on the other hand, hospitalization from graft to discharge from hospital cost savings with PBSC were about $10666. After discharge from hospital, costs were similar and cheaper in both groups. For the overall study the PBPC procedure was less expensive than ABMT, $35381 and $41759 respectively, with cost savings of $6378. The number of days spent in hospital and blood bank costs were the major cost factors. This study was based on a single pathology, non-Hodgkin's lymphoma, and the actual hospital records for each patient situation as opposed to a clinical trial, and our results were consistent with different previous studies carried out in different health care systems.

Modular Extracellular Matrices: Solutions for the Puzzle

PubMed Central

Serban, Monica A.; Prestwich, Glenn D.

2008-01-01

The common technique of growing cells in two-dimensions (2-D) is gradually being replaced by culturing cells on matrices with more appropriate composition and stiffness, or by encapsulation of cells in three-dimensions (3-D). The universal acceptance of the new 3-D paradigm has been constrained by the absence of a commercially available, biocompatible material that offers ease of use, experimental flexibility, and a seamless transition from in vitro to in vivo applications. The challenge – the puzzle that needs a solution – is to replicate the complexity of the native extracellular matrix (ECM) environment with the minimum number of components necessary to allow cells to rebuild and replicate a given tissue. For use in drug discovery, toxicology, cell banking, and ultimately in reparative medicine, the ideal matrix would therefore need to be highly reproducible, manufacturable, approvable, and affordable. Herein we describe the development of a set of modular components that can be assembled into biomimetic materials that meet these requirements. These semi-synthetic ECMs, or sECMs, are based on hyaluronan derivatives that form covalently crosslinked, biodegradable hydrogels suitable for 3-D culture of primary and stem cells in vitro, and for tissue formation in vivo. The sECMs can be engineered to provide appropriate biological cues needed to recapitulate the complexity of a given ECM environment. Specific applications for different sECM compositions include stem cell expansion with control of differentiation, scar-free wound healing, growth factor delivery, cell delivery for osteochondral defect and liver repair, and development of vascularized tumor xenografts for personalized chemotherapy. PMID:18442709

Conditioned medium: a new alternative for cryopreservation of equine umbilical cord mesenchymal stem cells.

PubMed

Maia, Leandro; Dias, Marianne Camargos; de Moraes, Carolina Nogueira; de Paula Freitas-Dell'Aqua, Camila; da Mota, Ligia S L Silveira; Santiloni, Valquíria; da Cruz Landim-Alvarenga, Fernanda

2017-03-01

Cryopreservation is a feasible alternative to maintaining several cell lines, particularly for immediate therapeutic use, transportation of samples, and implementation of new in vitro studies. This work parts from the hypothesis that the medium of cryopreservation composed by 90% of conditioned medium (CM) supports cryopreservation of equine umbilical cord intervascular matrix mesenchymal stem cells (UCIM-MSCs), allowing the maintenance of the biological properties for the establishment of cell banks intended for therapeutic use and in vitro studies. Thus, we evaluated the viability, apoptosis/necrosis rates, immunophenotypic profile (IP), chromosomal stability, clonicity, and differentiation potential of UCIM-MSCs cryopreserved with four different mediums (with FBS: M1, M3, M4 and without FBS: M2). After 3 months of cryopreservation, samples were thawed and analyzed. The potential of differentiation in the mesodermal lineages, clonicity, and the chromosomal stability were maintained after cryopreservation of UCIM-MSCs with medium containing FBS. Changes (P < 0.05) at IP for some markers were observed at cells cryopreserved with medium M1-M3. Only the UCIM-MSCs cryopreserved with the CM (M4) had similar viability post-thaw (P = 0.23) when compared with fresh cells. We proved the hypothesis that the medium of cryopreservation containing CM supports the cryopreservation of UCIM-MSCs, at the experimental conditions, being the medium that better maintains the biological characteristics observed at fresh cells. Thus, future studies of UCIM-MSCs secretome should be conducted to better understand the beneficial and protective effects of the CM during the freezing process. © 2017 International Federation for Cell Biology.

Types of Stem Cells

MedlinePlus

... Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

miRNA-regulated cancer stem cells: understanding the property and the role of miRNA in carcinogenesis.

PubMed

Chakraborty, Chiranjib; Chin, Kok-Yong; Das, Srijit

2016-10-01

Over the last few years, microRNAs (miRNA)-controlled cancer stem cells have drawn enormous attention. Cancer stem cells are a small population of tumor cells that possess the stem cell property of self-renewal. Recent data shows that miRNA regulates this small population of stem cells. In the present review, we explained different characteristics of cancer stem cells as well as miRNA regulation of self-renewal and differentiation in cancer stem cells. We also described the migration and tumor formation. Finally, we described the different miRNAs that regulate various types of cancer stem cells, such as prostate cancer stem cells, head and neck cancer stem cells, breast cancer stem cells, colorectal cancer stem cells, lung cancer stem cells, gastric cancer stem cells, pancreatic cancer stem cells, etc. Extensive research is needed in order to employ miRNA-based therapeutics to control cancer stem cell population in various cancers in the future.

What is a stem cell?

PubMed

Slack, Jonathan M W

2018-05-15

The historical roots of the stem cell concept are traced with respect to its usage in embryology and in hematology. The modern consensus definition of stem cells, comprising both pluripotent stem cells in culture and tissue-specific stem cells in vivo, is explained and explored. Methods for identifying stem cells are discussed with respect to cell surface markers, telomerase, label retention and transplantability, and properties of the stem cell niche are explored. The CreER method for identifying stem cells in vivo is explained, as is evidence in favor of a stochastic rather than an obligate asymmetric form of cell division. In conclusion, it is found that stem cells do not possess any unique and specific molecular markers; and stem cell behavior depends on the environment of the cell as well as the stem cell's intrinsic qualities. Furthermore, the stochastic mode of division implies that stem cell behavior is a property of a cell population not of an individual cell. In this sense, stem cells do not exist in isolation but only as a part of multicellular system. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells. © 2018 Wiley Periodicals, Inc.

Tissue Engineering Using Transfected Growth-Factor Genes

NASA Technical Reports Server (NTRS)

Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

Differential marker expression by cultures rich in mesenchymal stem cells

PubMed Central

2013-01-01

Background Mesenchymal stem cells have properties that make them amenable to therapeutic use. However, the acceptance of mesenchymal stem cells in clinical practice requires standardized techniques for their specific isolation. To date, there are no conclusive marker (s) for the exclusive isolation of mesenchymal stem cells. Our aim was to identify markers differentially expressed between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. We compared and contrasted the phenotype of tissue cultures in which mesenchymal stem cells are rich and rare. By initially assessing mesenchymal stem cell differentiation, we established that bone marrow and breast adipose cultures are rich in mesenchymal stem cells while, in our hands, foreskin fibroblast and olfactory tissue cultures contain rare mesenchymal stem cells. In particular, olfactory tissue cells represent non-stem cell mesenchymal cells. Subsequently, the phenotype of the tissue cultures were thoroughly assessed using immuno-fluorescence, flow-cytometry, proteomics, antibody arrays and qPCR. Results Our analysis revealed that all tissue cultures, regardless of differentiation potential, demonstrated remarkably similar phenotypes. Importantly, it was also observed that common mesenchymal stem cell markers, and fibroblast-associated markers, do not discriminate between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. Examination and comparison of the phenotypes of mesenchymal stem cell and non-stem cell mesenchymal cell cultures revealed three differentially expressed markers – CD24, CD108 and CD40. Conclusion We indicate the importance of establishing differential marker expression between mesenchymal stem cells and non-stem cell mesenchymal cells in order to determine stem cell specific markers. PMID:24304471

Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK.

PubMed

Castillejo-López, Casimiro; Delgado-Vega, Angélica M; Wojcik, Jerome; Kozyrev, Sergey V; Thavathiru, Elangovan; Wu, Ying-Yu; Sánchez, Elena; Pöllmann, David; López-Egido, Juan R; Fineschi, Serena; Domínguez, Nicolás; Lu, Rufei; James, Judith A; Merrill, Joan T; Kelly, Jennifer A; Kaufman, Kenneth M; Moser, Kathy L; Gilkeson, Gary; Frostegård, Johan; Pons-Estel, Bernardo A; D'Alfonso, Sandra; Witte, Torsten; Callejas, José Luis; Harley, John B; Gaffney, Patrick M; Martin, Javier; Guthridge, Joel M; Alarcón-Riquelme, Marta E

2012-01-01

Altered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis. The GPAT16 method was used to analyse the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein-protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.

Genetic and Physical Interaction of the B-Cell SLE-Associated Genes BANK1 and BLK

PubMed Central

Castillejo-López, Casimiro; Delgado-Vega, Angélica M.; Wojcik, Jerome; Kozyrev, Sergey V.; Thavathiru, Elangovan; Wu, Ying-Yu; Sánchez, Elena; Pöllmann, David; López-Egido, Juan R.; Fineschi, Serena; Domínguez, Nicolás; Lu, Rufei; James, Judith A.; Merrill, Joan T.; Kelly, Jennifer A.; Kaufman, Kenneth M.; Moser, Kathy; Gilkeson, Gary; Frostegård, Johan; Pons-Estel, Bernardo A.; D’Alfonso, Sandra; Witte, Torsten; Callejas, José Luis; Harley, John B.; Gaffney, Patrick; Martin, Javier; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.

2012-01-01

Objectives Altered signaling in B-cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signaling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterize the role of BANK1 and BLK in SLE, we performed a genetic interaction analysis hypothesizing that genetic interactions could reveal functional pathways relevant to disease pathogenesis. Methods We Used the method GPAT16 to analyze the gene-gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localization, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK. Results Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from Northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, we tested the possibility that BANK1 and BLK could also show a protein-protein interaction. We demonstrated co-immunoprecipitation and co-localization of BLK and BANK1. In a Daudi cell line and primary naïve B-cells the endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies. Conclusions Here, we show a genetic interaction between BANK1 and BLK, and demonstrate that these molecules interact physically. Our results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signaling pathway. PMID:21978998

Learn About Stem Cells

MedlinePlus

... Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... Home > Learn About Stem Cells > Stem Cell Basics Cells in the human body The human body comprises ...

Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

PubMed

Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

2015-01-01

Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

[Progress in stem cells and regenerative medicine].

PubMed

Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

2015-06-01

Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

Application of Graphene Based Nanotechnology in Stem Cells Research.

PubMed

Hu, Shanshan; Zeng, Yongxiang; Yang, Shuying; Qin, Han; Cai, He; Wang, Jian

2015-09-01

The past several years have witnessed significant advances in stem cell therapy, tissue engineering and regenerative medicine. Graphene, with its unique properties such as high electrical conductivity, elasticity and good molecule absorption, have potential for creating the next generation of biomaterials. This review summarizes the interrelationship between graphene and stem cells. The analysis of graphene when applied on mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, embryonic stem cells, periodontal ligament stem cells, human adipose-derived stem cells and cancer stem cells, and how graphene influences cell behavior and differentiation are discussed in details.

A revisionist history of adult marrow stem cell biology or 'they forgot about the discard'.

PubMed

Quesenberry, P; Goldberg, L

2017-08-01

The adult marrow hematopoietic stem cell biology has largely been based on studies of highly purified stem cells. This is unfortunate because during the stem cell purification the great bulk of stem cells are discarded. These cells are actively proliferating. The final purified stem cell is dormant and not representative of the whole stem cell compartment. Thus, a large number of studies on the cellular characteristics, regulators and molecular details of stem cells have been carried on out of non-represented cells. Niche studies have largely pursued using these purified stem cells and these are largely un-interpretable. Other considerations include the distinction between baseline and transplant stem cells and the modulation of stem cell phenotype by extracellular vesicles, to cite a non-inclusive list. Work needs to proceed on characterizing the true stem cell population.

Current and historical perspectives on methodological flaws in processing umbilical cord blood.

PubMed

Mehrishi, J N

2013-11-01

Umbilical cord blood (UCB) hematopoietic stem cells (HSC-CD34+) are valuable for treating malignant or nonmalignant disease. Processing UCB by HESPAN-6% and anti-CD34-Miltenyi particles provides insufficient cells for treating adults. Physicochemical-electrokinetic studies on UCB-mononuclear cells (MNCs) under conditions of delayed processing, ice or very low temperatures, and some cell separation media identified artifacts introduced by procedures. Adsorption of biomaterials from cell damage by temperature, degradation products after using enzymes, harsh reagents, dithiothreitol, and HESPAN affect cell properties and distribution. Miltenyi particles internalized by cells could release iron that accumulating in liver or spleen would then risk toxicity. Summary topics included the effects of temperature, HESPAN (fast sedimenting agent), glycoproteases, DNase, and dithiothreitol risk affecting cell receptors in recognition, "homing," leading to possible unintended iatrogenic bioeffects should such cells be transfused into humans. The loss of undetectable and uncaptured low CD34 antigen-bearing cells by Miltenyi particles seems to occur when the current methods of isolation of CD34+ cells and other cells are critically assessed. The purpose here is to highlight and suggest avoiding the procedural flaws involved. Preventing ice temperatures avoids ice-damaged platelets releasing biomaterials that are adsorbed on cells altering UBC-MNCs/HSC properties and cell loss. Omitting the positive selection with antibody-linked Miltenyi particles obviates the use of harsh reagents to release the cells. Internalized Miltenyi particles are a toxicity hazard that needs investigations. Achieving approximately 5% yields of CD34+ cells (153 × 10(5) /110 mL cord-placenta blood) is a major advance holding great promise, for the first time increasing the prospect of stem cell therapy of 70-kg adults, using a single UCB donation (with dose of 1.5 × 10(5) cells/kg) and considerably cheaper cultured red blood cells manufacture (multiple packs/2 × 10(12) ). © 2013 American Association of Blood Banks.

Perspectives on stem cell therapy for cardiac regeneration. Advances and challenges.

PubMed

Choi, Sung Hyun; Jung, Seok Yun; Kwon, Sang-Mo; Baek, Sang Hong

2012-01-01

Ischemic heart disease (IHD) accelerates cardiomyocyte loss, but the developing stem cell research could be useful for regenerating a variety of tissue cells, including cardiomyocytes. Diverse sources of stem cells for IHD have been reported, including embryonic stem cells, induced pluripotent stem cells, skeletal myoblasts, bone marrow-derived stem cells, mesenchymal stem cells, and cardiac stem cells. However, stem cells have unique advantages and disadvantages for cardiac tissue regeneration, which are important considerations in determining the specific cells for improving cell survival and long-term engraftment after transplantation. Additionally, the dosage and administration method of stem cells need to be standardized to increase stability and efficacy for clinical applications. Accordingly, this review presents a summary of the stem cell therapies that have been studied for cardiac regeneration thus far, and discusses the direction of future cardiac regeneration research for stem cells.

Stem Cells

MedlinePlus

Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

The Role of Integrin α6 (CD49f) in Stem Cells: More than a Conserved Biomarker.

PubMed

Krebsbach, Paul H; Villa-Diaz, Luis G

2017-08-01

Stem cells have the capacity for self-renewal and differentiation into specialized cells that form and repopulated all tissues and organs, from conception to adult life. Depending on their capacity for differentiation, stem cells are classified as totipotent (ie, zygote), pluripotent (ie, embryonic stem cells), multipotent (ie, neuronal stem cells, hematopoietic stem cells, epithelial stem cells, etc.), and unipotent (ie, spermatogonial stem cells). Adult or tissue-specific stem cells reside in specific niches located in, or nearby, their organ or tissue of origin. There, they have microenvironmental support to remain quiescent, to proliferate as undifferentiated cells (self-renewal), and to differentiate into progenitors or terminally differentiated cells that migrate from the niche to perform specialized functions. The presence of proteins at the cell surface is often used to identify, classify, and isolate stem cells. Among the diverse groups of cell surface proteins used for these purposes, integrin α6, also known as CD49f, may be the only biomarker commonly found in more than 30 different populations of stem cells, including some cancer stem cells. This broad expression among stem cell populations indicates that integrin α6 may play an important and conserved role in stem cell biology, which is reaffirmed by recent demonstrations of its role maintaining self-renewal of pluripotent stem cells and breast and glioblastoma cancer stem cells. Therefore, this review intends to highlight and synthesize new findings on the importance of integrin α6 in stem cell biology.

Phylogenetic analysis of the complete genome of 11 BKV isolates obtained from allogenic stem cell transplant recipients in Ireland.

PubMed

Drew, Richard John; Walsh, Anne; Laoi, Bairbre Ni; Crowley, Brendan

2012-07-01

BK polyomavirus (family Polyomaviridae) may cause hemorrhagic cystitis (BKV-HC) in hematopoietic stem cell transplant recipients. Eleven complete BKV genomes (GenBank accession numbers: JN192431-JN192441) were sequenced from urine samples of allogenic hematopoietic stem cell transplant recipients and compared to complete BKV genomes in the published literature. Of the 11 isolates, seven (64%) were subgroup Ib-1, three (27%) isolates belonged to subgroup Ib-2 and a single isolate belonged to subtype III. The analysis of single-nucleotide polymorphisms in this study showed that isolates could be subclassified into subtypes I-IV and subgroups Ib-1 and Ib-2 on the basis of VP1 of the first part of the Large T-antigen (LTag). The non-coding control region (NCCR) of the 11 isolates was also sequenced. These sequences showed that there was consistent sequence homology within subgroups Ib-1 and Ib-2. Two new mutations were described in the isolates, G→C at O(84) in isolate SJH-LG-310, and a deletion at R(2-7) in isolate SJH-LG-309. No known transcription factor is thought to be present at the site of either of these mutations. There were no rearrangements seen in isolates and this may be because the patients were not followed up over time. There were five nucleotide positions at which subgroup Ib-1 isolated differed from subgroup Ib-2 isolates in the NCCR sequence, O(41) , P(18) , P(31) , R(4) , and S(18) . The mutation O(41) is present in the promoter granulocyte/macrophage stimulating factor) gene and the P(31) mutation is present in the NF-1 gene. Copyright © 2012 Wiley Periodicals, Inc.

Drosophila's contribution to stem cell research.

PubMed

Singh, Gyanesh

2015-01-01

The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. Recent developments in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila.

Drosophila's contribution to stem cell research

PubMed Central

Singh, Gyanesh

2016-01-01

The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. Recent developments in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila. PMID:26180635

Geomorphic responses of Duluth-area streams to the June 2012 flood, Minnesota

USGS Publications Warehouse

Fitzpatrick, Faith A.; Ellison, Christopher A.; Czuba, Christiana R.; Young, Benjamin M.; McCool, Molly M.; Groten, Joel T.

2016-09-01

In 2013, the U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a geomorphic assessment of 51 Duluth-area stream sites in 20 basins to describe and document the stream geomorphic changes associated with the June 2012 flood. Heavy rainfall caused flood peaks with annual exceedance probabilities of less than 0.002 (flood recurrence interval of greater than 500 years) on large and small streams in and surrounding the Duluth area. A geomorphic segment-scale classification previously developed in 2003–4 by the U.S. Geological Survey for Duluth-area streams was used as a framework to characterize the observed flood-related responses along a longitudinal continuum from headwaters to rivermouths at Lake Superior related to drainage network position, slope, geologic setting, and valley type. Field assessments in 2013 followed and expanded on techniques used in 2003–4 at intensive and rapid sites. A third level of assessment was added in 2013 to increase the amount of quantitative data at a subset of 2003–4 rapid sites. Characteristics of channel morphology, channel bed substrate, exposed bars and soft sediment deposition, large wood, pools, and bank erosion were measured; and repeat photographs were taken. Additional measurements in 2013 included identification of Rosgen Level II stream types. The comparative analyses of field data collected in 2003–4 and again in 2013 indicated notable geomorphic changes, some of them expected and others not. As expected, in headwaters with gently sloping wetland segments, geomorphic changes were negligible (little measured or observed change). Downstream, middle main stems generally had bank and bluff erosion and bar formation as expected. Steep bedrock sites along middle and lower main stems had localized bank and bluff erosion in short sections with intermittent bedrock. Lower main stem and alluvial sites had bank erosion, widening, gravel bar deposition, and aggradation. Bar formation and accumulation of gravel was more widespread than expected among all main stems, especially for sites upstream and downstream from channel constrictions from road crossings, or even steep sites with localized, more gently sloping sections. Decreases in large wood and pools also were observed throughout the longitudinal continuum of main-stem sites, with immediate implications for fish and benthic invertebrate aquatic habitat. Whether or not the geomorphic conditions will return to their preflood condition depends on the location along the longitudinal continuum. The amount of large wood and pools may return after more moderate floods, whereas bars with coarse material may remain in place, locally altering flow direction and causing continued bank erosion. Results from this study can be used by local managers in postflood reconstruction efforts and provide baseline information for continued monitoring of geomorphic responses to the June 2012 flood.

The longest telomeres: a general signature of adult stem cell compartments

PubMed Central

Flores, Ignacio; Canela, Andres; Vera, Elsa; Tejera, Agueda; Cotsarelis, George; Blasco, María A.

2008-01-01

Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine. However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age. PMID:18283121

Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells.

PubMed

Zeisberger, Steffen M; Schulz, Julia C; Mairhofer, Mario; Ponsaerts, Peter; Wouters, Guy; Doerr, Daniel; Katsen-Globa, Alisa; Ehrbar, Martin; Hescheler, Jurgen; Hoerstrup, Simon P; Zisch, Andreas H; Kolbus, Andrea; Zimmermann, Heiko

2011-01-01

While therapeutic cell transplantations using progenitor cells are increasingly evolving towards phase I and II clinical trials and chemically defined cell culture is established, standardization in biobanking is still in the stage of infancy. In this study, the EU FP6-funded CRYSTAL (CRYo-banking of Stem cells for human Therapeutic AppLication) consortium aimed to validate novel Standard Operating Procedures (SOPs) to perform and validate xeno-free and chemically defined cryopreservation of human progenitor cells and to reduce the amount of the potentially toxic cryoprotectant additive (CPA) dimethyl sulfoxide (DMSO). To achieve this goal, three human adult progenitor and stem cell populations-umbilical cord blood (UCB)-derived erythroid cells (UCB-ECs), UCB-derived endothelial colony forming cells (UCB-ECFCs), and adipose tissue (AT)-derived mesenchymal stromal cells (AT-MSCs)-were cryopreserved in chemically defined medium supplemented with 10% or 5% DMSO. Cell recovery, cell repopulation, and functionality were evaluated postthaw in comparison to cryopreservation in standard fetal bovine serum (FBS)-containing freezing medium. Even with a reduction of the DMSO CPA to 5%, postthaw cell count and viability assays indicated no overall significant difference versus standard cryomedium. Additionally, to compare cellular morphology/membrane integrity and ice crystal formation during cryopreservation, multiphoton laser-scanning cryomicroscopy (cryo-MPLSM) and scanning electron microscopy (SEM) were used. Neither cryo-MPLSM nor SEM indicated differences in membrane integrity for the tested cell populations under various conditions. Moreover, no influence was observed on functional properties of the cells following cryopreservation in chemically defined freezing medium, except for UCB-ECs, which showed a significantly reduced differentiation capacity after cryopreservation in chemically defined medium supplemented with 5% DMSO. In summary, these results demonstrate the feasibility and robustness of standardized xeno-free cryopreservation of different human progenitor cells and encourage their use even more in the field of tissue-engineering and regenerative medicine.

Context clues: the importance of stem cell-material interactions

PubMed Central

Murphy, William L.

2014-01-01

Understanding the processes by which stem cells give rise to de novo tissues is an active focus of stem cell biology and bioengineering disciplines. Instructive morphogenic cues surrounding the stem cell during morphogenesis create what is referred to as the stem cell microenvironment. An emerging paradigm in stem cell bioengineering involves “biologically driven assembly,” in which stem cells are encouraged to largely define their own morphogenesis processes. However, even in the case of biologically driven assembly, stem cells do not act alone. The properties of the surrounding microenvironment can be critical regulators of cell fate. Stem cell-material interactions are among the most well-characterized microenvironmental effectors of stem cell fate, and they establish a signaling “context” that can define the mode of influence for morphogenic cues. Here we describe illustrative examples of cell-material interactions that occur during in vitro stem cell studies, with an emphasis on how cell-material interactions create instructive contexts for stem cell differentiation and morphogenesis. PMID:24369691

Cancer stem cells and differentiation therapy.

PubMed

Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-10-01

Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

Clinical trials for stem cell transplantation: when are they needed?

PubMed

Van Pham, Phuc

2016-04-27

In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

Stem cells - biological update and cell therapy progress

PubMed Central

GIRLOVANU, MIHAI; SUSMAN, SERGIU; SORITAU, OLGA; RUS-CIUCA, DAN; MELINCOVICI, CARMEN; CONSTANTIN, ANNE-MARIE; MIHU, CARMEN MIHAELA

2015-01-01

In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research. The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases. Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues. This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine. PMID:26609255

Establishment of mouse expanded potential stem cells

PubMed Central

Gao, Xuefei; Antunes, Liliana; Yu, Yong; Zhu, Zhexin; Wang, Juexuan; Kolodziejczyk, Aleksandra A.; Campos, Lia S.; Wang, Cui; Yang, Fengtang; Zhong, Zhen; Fu, Beiyuan; Eckersley-Maslin, Melanie A.; Woods, Michael; Tanaka, Yosuke; Chen, Xi; Wilkinson, Adam C.; Bussell, James; White, Jacqui; Ramirez-Solis, Ramiro; Reik, Wolf; Göttgens, Berthold; Teichmann, Sarah A.; Tam, Patrick P. L.; Nakauchi, Hiromitsu; Zou, Xiangang; Lu, Liming; Liu, Pentao

2018-01-01

Mouse embryonic stem cells derived from the epiblast1 contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm2 upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species. PMID:29019987

Adult Stem Cell Therapy for Stroke: Challenges and Progress

PubMed Central

Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

2016-01-01

Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

Restoring the quantity and quality of elderly human mesenchymal stem cells for autologous cell-based therapies.

PubMed

Block, Travis J; Marinkovic, Milos; Tran, Olivia N; Gonzalez, Aaron O; Marshall, Amanda; Dean, David D; Chen, Xiao-Dong

2017-10-27

Degenerative diseases are a major public health concern for the aging population and mesenchymal stem cells (MSCs) have great potential for treating many of these diseases. However, the quantity and quality of MSCs declines with aging, limiting the potential efficacy of autologous MSCs for treating the elderly population. Human bone marrow (BM)-derived MSCs from young and elderly donors were obtained and characterized using standard cell surface marker criteria (CD73, CD90, CD105) as recommended by the International Society for Cellular Therapy (ISCT). The elderly MSC population was isolated into four subpopulations based on size and stage-specific embryonic antigen-4 (SSEA-4) expression using fluorescence-activated cell sorting (FACS), and subpopulations were compared to the unfractionated young and elderly MSCs using assays that evaluate MSC proliferation, quality, morphology, intracellular reactive oxygen species, β-galactosidase expression, and adenosine triphosphate (ATP) content. The ISCT-recommended cell surface markers failed to detect any differences between young and elderly MSCs. Here, we report that elderly MSCs were larger in size and displayed substantially higher concentrations of intracellular reactive oxygen species and β-galactosidase expression and lower amounts of ATP and SSEA-4 expression. Based on these findings, cell size and SSEA-4 expression were used to separate the elderly MSCs into four subpopulations by FACS. The original populations (young and elderly MSCs), as well as the four subpopulations, were then characterized before and after culture on tissue culture plastic and BM-derived extracellular matrix (BM-ECM). The small SSEA-4-positive subpopulation representing ~ 8% of the original elderly MSC population exhibited a "youthful" phenotype that was similar to that of young MSCs. The biological activity of this elderly subpopulation was inhibited by senescence-associated factors produced by the unfractionated parent population. After these "youthful" cells were isolated and expanded (three passages) on a "young microenvironment" (i.e., BM-ECM produced by BM cells from young donors), the number of cells increased ≈ 17,000-fold to 3 × 10 9 cells and retained their "youthful" phenotype. These results suggest that it is feasible to obtain large numbers of high-quality autologous MSCs from the elderly population and establish personal stem cell banks that will allow serial infusions of "rejuvenated" MSCs for treating age-related diseases.

Two sides of the same coin? Unraveling subtle differences between human embryonic and induced pluripotent stem cells by Raman spectroscopy.

PubMed

Parrotta, Elvira; De Angelis, Maria Teresa; Scalise, Stefania; Candeloro, Patrizio; Santamaria, Gianluca; Paonessa, Mariagrazia; Coluccio, Maria Laura; Perozziello, Gerardo; De Vitis, Stefania; Sgura, Antonella; Coluzzi, Elisa; Mollace, Vincenzo; Di Fabrizio, Enzo Mario; Cuda, Giovanni

2017-11-28

Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, hold enormous promise for many biomedical applications, such as regenerative medicine, drug testing, and disease modeling. Although induced pluripotent stem cells resemble embryonic stem cells both morphologically and functionally, the extent to which these cell lines are truly equivalent, from a molecular point of view, remains controversial. Principal component analysis and K-means cluster analysis of collected Raman spectroscopy data were used for a comparative study of the biochemical fingerprint of human induced pluripotent stem cells and human embryonic stem cells. The Raman spectra analysis results were further validated by conventional biological assays. Raman spectra analysis revealed that the major difference between human embryonic stem cells and induced pluripotent stem cells is due to the nucleic acid content, as shown by the strong positive peaks at 785, 1098, 1334, 1371, 1484, and 1575 cm -1 , which is enriched in human induced pluripotent stem cells. Here, we report a nonbiological approach to discriminate human induced pluripotent stem cells from their native embryonic stem cell counterparts.

A family business: stem cell progeny join the niche to regulate homeostasis.

PubMed

Hsu, Ya-Chieh; Fuchs, Elaine

2012-01-23

Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

A family business: stem cell progeny join the niche to regulate homeostasis

PubMed Central

Hsu, Ya-Chieh; Fuchs, Elaine

2012-01-01

Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems. PMID:22266760

Stem Cell Therapy for Erectile Dysfunction.

PubMed

Matz, Ethan L; Terlecki, Ryan; Zhang, Yuanyuan; Jackson, John; Atala, Anthony

2018-04-06

The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects. Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research. The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed. Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively. Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function. The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.

PubMed

Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

2012-12-01

According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.

Adult bone marrow-derived stem cells for organ regeneration and repair.

PubMed

Tögel, Florian; Westenfelder, Christof

2007-12-01

Stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies. There are in general two types of stem cells, embryonic and adult stem cells. While embryonic stem cell therapy has been riddled with problems of allogeneic rejection and ethical concerns, adult stem cells have long been used in the treatment of hematological malignancies. With the recognition of additional, potentially therapeutic characteristics, bone marrow-derived stem cells have become a tool in regenerative medicine. The bone marrow is an ideal source of stem cells because it is easily accessible and harbors two types of stem cells. Hematopoietic stem cells give rise to all blood cell types and have been shown to exhibit plasticity, while multipotent marrow stromal cells are the source of osteocytes, chondrocytes, and fat cells and have been shown to support and generate a large number of different cell types. This review describes the general characteristics of these stem cell populations and their current and potential future applications in regenerative medicine. 2007 Wiley-Liss, Inc

Stem cells.

PubMed

Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

2010-10-01

Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

Some Ethical Concerns About Human Induced Pluripotent Stem Cells.

PubMed

Zheng, Yue Liang

2016-10-01

Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy.

Laser biomodulation on stem cells

NASA Astrophysics Data System (ADS)

Liu, Timon C.; Duan, Rui; Li, Yan; Li, Xue-Feng; Tan, Li-Ling; Liu, Songhao

2001-08-01

Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

PubMed

Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

2012-08-01

As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

In vitro differentiation of primordial germ cells and oocyte-like cells from stem cells.

PubMed

Costa, José J N; Souza, Glaucinete B; Soares, Maria A A; Ribeiro, Regislane P; van den Hurk, Robert; Silva, José R V

2018-02-01

Infertility is the result of failure due to an organic disorder of the reproductive organs, especially their gametes. Recently, much progress has been made on generating germ cells, including oocytes, from various types of stem cells. This review focuses on advances in female germ cell differentiation from different kinds of stem cells, with emphasis on embryonic stem cells, adult stem cells, and induced pluripotent stem cells. The advantages and disadvantages of the derivation of female germ cells from several types of stem cells are also highlighted, as well as the ability of stem cells to generate mature and functional female gametes. This review shows that stem cell therapies have opened new frontiers in medicine, especially in the reproductive area, with the possibility of regenerating fertility.

Reduced hematopoietic stem cell frequency predicts outcome in acute myeloid leukemia.

PubMed

Wang, Wenwen; Stiehl, Thomas; Raffel, Simon; Hoang, Van T; Hoffmann, Isabel; Poisa-Beiro, Laura; Saeed, Borhan R; Blume, Rachel; Manta, Linda; Eckstein, Volker; Bochtler, Tilmann; Wuchter, Patrick; Essers, Marieke; Jauch, Anna; Trumpp, Andreas; Marciniak-Czochra, Anna; Ho, Anthony D; Lutz, Christoph

2017-09-01

In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients who achieved durable remissions. However, in patients who eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker of minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells have increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing the dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse. Copyright© 2017 Ferrata Storti Foundation.

Evaluation of the secretion and release of vascular endothelial growth factor from two-dimensional culture and three-dimensional cell spheroids formed with stem cells and osteoprecursor cells.

PubMed

Lee, Hyunjin; Lee, Sung-Il; Ko, Youngkyung; Park, Jun-Beom

2018-05-18

Co-culture has been applied in cell therapy, including stem cells, and has been reported to give enhanced functionality. In this study, stem-cell spheroids were formed in concave micromolds at different ratios of stem cells to osteoprecursor cells, and the amount of secretion of vascular endothelial growth factor (VEGF) was evaluated. Gingiva-derived stem cells and osteoprecursor cells in the amount of 6 × 105 were seeded on a 24-well culture plate or concave micromolds. The ratios of stem cells to osteoprecursor cells included: 0:4 (group 1), 1:3 (group 2), 2:2 (group 3), 3:1 (group 4), and 4:0 (group 5). The morphology of cells in a 2-dimensional culture (groups 1-5) showed a fibroblast-like appearance. The secretion of VEGF increased with the increase in stem cells, and a statistically significant increase was noted in groups 3, 4 and 5 when compared with the media-only group (p < 0.05). Osteoprecursor cells formed spheroids in concave microwells, and no noticeable change in the morphology was noted with the increase in stem cells. Spheroids containing stem cells were positive for the stem-cell markers SSEA-4. The secretion of VEGF from cell spheroids increased with the increase in stem cells. This study showed that cell spheroids formed with stem cells and osteoprecursor cells with different ratios, using microwells, had paracrine effects on the stem cells. The secretion of VEGF increased with the increase in stem cells. This stem-cell spheroid may be applied for tissue-engineering purposes.

The Role of Stem Cells in Aesthetic Surgery: Fact or Fiction?

PubMed Central

McArdle, Adrian; Senarath-Yapa, Kshemendra; Walmsley, Graham G.; Hu, Michael; Atashroo, David A.; Tevlin, Ruth; Zielins, Elizabeth; Gurtner, Geoffrey C.; Wan, Derrick C.; Longaker, Michael T.

2014-01-01

Stem cells are attractive candidates for the development of novel therapies, targeting indications that involve functional restoration of defective tissue. Although most stem cell therapies are new and highly experimental, there are clinics around the world that exploit vulnerable patients with the hope of offering supposed stem cell therapies, many of which operate without credible scientific merit, oversight, or other patient protection. We review the potential, as well as drawbacks, for incorporation of stem cells in cosmetic procedures. A review of FDA-approved indications and ongoing clinical trials with adipose stem cells is provided. Furthermore, a “snapshot” analysis of websites using the search terms “stem cell therapy” or “stem cell treatment” or “stem cell facelift” was performed. Despite the protective net cast by regulatory agencies such as the FDA and professional societies such as the American Society of Plastic Surgeons, we are witnessing worrying advertisements for procedures such as stem cell facelifts, stem cell breast augmentations, and even stem cell vaginal rejuvenation. The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence in the majority of cases. Stem cells offer tremendous potential, but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk. With plastic surgeons at the forefront of stem cell-based regenerative medicine, it is critically important that we provide an example of a rigorous approach to research, data collection, and advertising of stem cell therapies. PMID:24732654

A WUSCHEL-Independent Stem Cell Specification Pathway Is Repressed by PHB, PHV and CNA in Arabidopsis.

PubMed

Lee, Chunghee; Clark, Steven E

2015-01-01

The homeostatic maintenance of stem cells that carry out continuous organogenesis at the shoot meristem is crucial for plant development. Key known factors act to signal between the stem cells and an underlying group of cells thought to act as the stem cell niche. In Arabidopsis thaliana the homeodomain transcription factor WUSCHEL (WUS) is essential for stem cell initiation and maintenance at shoot and flower meristems. Recent data suggest that the WUS protein may move from the niche cells directly into the stem cells to maintain stem cell identity. Here we provide evidence for a second, previously unknown, pathway for stem cell specification at shoot and flower meristems that bypasses the requirement for WUS. We demonstrate that this novel stem cell specification pathway is normally repressed by the activity of the HD-zip III transcription factors PHABULOSA (PHB), PHAVOLUTA (PHV) and CORONA (CNA). When de-repressed, this second stem cell pathway leads to an accumulation of stem cells and an enlargement of the stem cell niche. When de-repressed in a wus mutant background, this second stem cell pathway leads to functional meristems with largely normal cell layering and meristem morphology, activation of WUS cis regulatory elements, and extensive, but not indeterminate, organogenesis. Thus, WUS is largely dispensable for stem cell specification and meristem function, suggesting a set of key stem cell specification factors, competitively regulated by WUS and PHB/PHV/CNA, remain unidentified.

A WUSCHEL-Independent Stem Cell Specification Pathway Is Repressed by PHB, PHV and CNA in Arabidopsis

PubMed Central

Lee, Chunghee; Clark, Steven E.

2015-01-01

The homeostatic maintenance of stem cells that carry out continuous organogenesis at the shoot meristem is crucial for plant development. Key known factors act to signal between the stem cells and an underlying group of cells thought to act as the stem cell niche. In Arabidopsis thaliana the homeodomain transcription factor WUSCHEL (WUS) is essential for stem cell initiation and maintenance at shoot and flower meristems. Recent data suggest that the WUS protein may move from the niche cells directly into the stem cells to maintain stem cell identity. Here we provide evidence for a second, previously unknown, pathway for stem cell specification at shoot and flower meristems that bypasses the requirement for WUS. We demonstrate that this novel stem cell specification pathway is normally repressed by the activity of the HD-zip III transcription factors PHABULOSA (PHB), PHAVOLUTA (PHV) and CORONA (CNA). When de-repressed, this second stem cell pathway leads to an accumulation of stem cells and an enlargement of the stem cell niche. When de-repressed in a wus mutant background, this second stem cell pathway leads to functional meristems with largely normal cell layering and meristem morphology, activation of WUS cis regulatory elements, and extensive, but not indeterminate, organogenesis. Thus, WUS is largely dispensable for stem cell specification and meristem function, suggesting a set of key stem cell specification factors, competitively regulated by WUS and PHB/PHV/CNA, remain unidentified. PMID:26011610

Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells.

PubMed

Zhang, Zhenzhen; Liu, Jianfang; Liu, Yang; Li, Zheng; Gao, Wei-Qiang; He, Zuping

2013-02-01

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end-stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end-stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra-hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra-hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. Copyright © 2012 Wiley Periodicals, Inc.

Stem cells in dentistry--part I: stem cell sources.

PubMed

Egusa, Hiroshi; Sonoyama, Wataru; Nishimura, Masahiro; Atsuta, Ikiru; Akiyama, Kentaro

2012-07-01

Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties. Copyright © 2012 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Plant stem cell niches.

PubMed

Stahl, Yvonne; Simon, Rüdiger

2005-01-01

Stem cells are required to support the indeterminate growth style of plants. Meristems are a plants stem cell niches that foster stem cell survival and the production of descendants destined for differentiation. In shoot meristems, stem cell fate is decided at the populational level. The size of the stem cell domain at the meristem tip depends on signals that are exchanged with cells of the organizing centre underneath. In root meristems, individual stem cells are controlled by direct interaction with cells of the quiescent centre that lie in the immediate neighbourhood. Analysis of the interactions and signaling processes in the stem cell niches has delivered some insights into the molecules that are involved and revealed that the two major niches for plant stem cells are more similar than anticipated.

Testicular tissue cryopreservation and spermatogonial stem cell transplantation to restore fertility: from bench to bedside

PubMed Central

2014-01-01

Male infertility management has made significant progress during the past three decades, especially after the introduction of intracytoplasmic sperm injection in 1992. However, many boys and men still suffer from primary testicular failure due to acquired or genetic causes. New and novel treatments are needed to address these issues. Spermatogenesis originates from spermatogonial stem cells (SSCs) that reside in the testis. Many of these men lack SSCs or have lost SSCs over time as a result of specific medical conditions or toxic exposures. Loss of SSCs is critical in prepubertal boys who suffer from cancer and are going through gonadotoxic cancer treatments, as there is no option of sperm cryopresrvation due to sexual immaturity. The development of SSC transplantation in a mouse model to repopulate spermatozoa in depleted testes has opened new avenues of research in other animal models, including non-human primates. Recent advances in cryopreservation and in vitro propagation of human SSCs offer promise for human SSC autotransplantation in the near future. Ongoing research is focusing on safety and technical issues of human SSC autotransplantation. This is the time to counsel parents and boys at risk of infertility on the possibility of cryopreserving and banking a small amount of testis tissue for potential future use in SSC transplantation. PMID:25157677

Stem cells in the Drosophila digestive system.

PubMed

Zeng, Xiankun; Chauhan, Chhavi; Hou, Steven X

2013-01-01

Adult stem cells maintain tissue homeostasis by continuously replenishing damaged, aged and dead cells in any organism. Five types of region and organ-specific multipotent adult stem cells have been identified in the Drosophila digestive system: intestinal stem cells (ISCs) in the posterior midgut; hindgut intestinal stem cells (HISCs) at the midgut/hindgut junction; renal and nephric stem cells (RNSCs) in the Malpighian Tubules; type I gastric stem cells (GaSCs) at foregut/midgut junction; and type II gastric stem cells (GSSCs) at the middle of the midgut. Despite the fact that each type of stem cell is unique to a particular organ, they share common molecular markers and some regulatory signaling pathways. Due to the simpler tissue structure, ease of performing genetic analysis, and availability of abundant mutants, Drosophila serves as an elegant and powerful model system to study complex stem cell biology. The recent discoveries, particularly in the Drosophila ISC system, have greatly advanced our understanding of stem cell self-renewal, differentiation, and the role of stem cells play in tissue homeostasis/regeneration and adaptive tissue growth.

Induced cancer stem cells generated by radiochemotherapy and their therapeutic implications.

PubMed

Chen, Xiewan; Liao, Rongxia; Li, Dezhi; Sun, Jianguo

2017-03-07

Local and distant recurrence of malignant tumors following radio- and/or chemotherapy correlates with poor prognosis of patients. Among the reasons for cancer recurrence, preexisting cancer stem cells (CSCs) are considered the most likely cause due to their properties of self-renewal, pluripotency, plasticity and tumorigenicity. It has been demonstrated that preexisting cancer stem cells derive from normal stem cells and differentiated somatic cells that undergo transformation and dedifferentiation respectively under certain conditions. However, recent studies have revealed that cancer stem cells can also be induced from non-stem cancer cells by radiochemotherapy, constituting the subpopulation of induced cancer stem cells (iCSCs). These findings suggest that radiochemotherapy has the side effect of directly transforming non-stem cancer cells into induced cancer stem cells, possibly contributing to tumor recurrence and metastasis. Therefore, drugs targeting cancer stem cells or preventing dedifferentiation of non-stem cancer cells can be combined with radiochemotherapy to improve its antitumor efficacy. The current review is to investigate the mechanisms by which induced cancer stem cells are generated by radiochemotherapy and hence provide new strategies for cancer treatment.

Stem cells in gastroenterology and hepatology

PubMed Central

Quante, Michael; Wang, Timothy C.

2010-01-01

Cellular and tissue regeneration in the gastrointestinal tract and liver depends on stem cells with properties of longevity, self-renewal and multipotency. Progress in stem cell research and the identification of potential esophageal, gastric, intestinal, colonic, hepatic and pancreatic stem cells provides hope for the use of stem cells in regenerative medicine and treatments for disease. Embryonic stem cells and induced pluripotent stem cells have the potential to give rise to any cell type in the human body, but their therapeutic application remains challenging. The use of adult or tissue-restricted stem cells is emerging as another possible approach for the treatment of gastrointestinal diseases. The same self-renewal properties that allow stem cells to remain immortal and generate any tissue can occasionally make their proliferation difficult to control and make them susceptible to malignant transformation. This Review provides an overview of the different types of stem cell, focusing on tissue-restricted adult stem cells in the fields of gastroenterology and hepatology and summarizing the potential benefits and risks of using stems cells to treat gastroenterological and liver disorders. PMID:19884893

Lower Oncogenic Potential of Human Mesenchymal Stem Cells Derived from Cord Blood Compared to Induced Pluripotent Stem Cells

PubMed Central

Foroutan, T.; Najmi, M.; Kazemi, N.; Hasanlou, M.; Pedram, A.

2015-01-01

Background: In regenerative medicine, use of each of the mesenchymal stem cells derived from bone marrow, cord blood, and adipose tissue, has several cons and pros. Mesenchymal stem cells derived from cord blood have been considered the best source for precursor transplantation. Direct reprogramming of a somatic cell into induced pluripotent stem cells by over-expression of 6 transcription factors Oct4, Sox2, Klf4, lin28, Nanog, and c-Myc has great potential for regenerative medicine, eliminating the ethical issues of embryonic stem cells and the rejection problems of using non-autologous cells. Objective: To compare reprogramming and pluripotent markers OCT4, Sox-2, c-Myc, Klf4, Nanog, and lin28 in mesenchymal stem cells derived from cord blood and induced pluripotent stem cells. Methods: We analyzed the expression level of OCT4, Sox-2, c-Myc, Klf4, Nanog and lin28 genes in human mesenchymal stem cells derived from cord blood and induced pluripotent stem cells by cell culture and RT-PCR. Results: The expression level of pluripotent genes OCT4 and Sox-2, Nanog and lin28 in mesenchymal stem cells derived from cord blood were significantly higher than those in induced pluripotent stem cells. In contrast to OCT-4A and Sox-2, Nanog and lin28, the expression level of oncogenic factors c-Myc and Klf4 were significantly higher in induced pluripotent stem cells than in mesenchymal stem cells derived from cord blood. Conclusion: It could be concluded that mesenchymal stem cells derived from human cord blood have lower oncogenic potential compared to induced pluripotent stem cells. PMID:26306155

Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hyun, Kyung-Hwan; Yoon, Chang-Hwan; Kim, Rae-Kwon

A subpopulation of cancer cells with stem cell properties is responsible for tumor maintenance and progression, and may contribute to resistance to anticancer treatments. Thus, compounds that target cancer stem-like cells could be usefully applied to destroy cancer. In this study, we investigated the effect of Eckol, a phlorotannin compound, on stemness and malignancies in glioma stem-like cells. To determine whether Eckol targets glioma stem-like cells, we examined whether Eckol treatment could change the expression levels of glioma stem-like cell markers and self-renewal-related proteins as well as the sphere forming ability, and the sensitivity to anticancer treatments. Alterations in themore » malignant properties of sphere-derived cells by Eckol were also investigated by soft-agar colony forming assay, by xenograft assay in nude mice, and by cell invasion assay. Treatment of sphere-forming glioma cells with Eckol effectively decreased the sphere formation as well as the CD133{sup +} cell population. Eckol treatment suppressed expression of the glioma stem-like cell markers and the self-renewal-related proteins without cell death. Moreover, treatment of glioma stem-like cells with Eckol significantly attenuated anchorage-independent growth on soft agar and tumor formation in xenograft mice. Importantly, Eckol treatment effectively reduced the resistance of glioma stem-like cells to ionizing radiation and temozolomide. Treatment of glioma stem-like cells with Eckol markedly blocked both phosphoinositide 3-kinase-Akt and Ras-Raf-1-Erk signaling pathways. These results indicate that the natural phlorotannin Eckol suppresses stemness and malignancies in glioma stem-like cells, and thereby makes glioma stem-like cells more sensitive to anticancer treatments, providing novel therapeutic strategies targeting specifically cancer stem-like cells.« less

Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model.

PubMed

Linard, Christine; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Benderitter, Marc

2016-09-01

The success of mesenchymal stem cell transplantation for proctitis depends not only on cell donors but also on host microenvironmental factors, which play a major role in conditioning mesenchymal stem cell immunosuppressive action and repair. This study sought to determine if flagellin, a TLR5 ligand, can enhance the mesenchymal stem cell treatment efficacy in radiation-induced proctitis. With the use of a colorectal model of 27 Gy irradiation in rats, we investigated and compared the effects on immune capacity and remodeling at 28 d after irradiation of the following: 1) systemic mesenchymal stem cell (5 × 10(6)) administration at d 7 after irradiation, 2) administration of flagellin at d 3 and systemic mesenchymal stem cell administration at d 7, and 3) in vitro preconditioning of mesenchymal stem cells with flagellin, 24 h before their administration on d 7. The mucosal CD8(+) T cell population was normalized after treatment with flagellin-preconditioned mesenchymal stem cells or flagellin plus mesenchymal stem cells, whereas mesenchymal stem cells alone did not alter the radiation-induced elevation of CD8(+) T cell frequency. Mesenchymal stem cell treatment returned the irradiation-elevated frequency of CD25(+) cells in the mucosa-to-control levels, whereas both flagellin-preconditioned mesenchymal stem cell and flagellin-plus-mesenchymal stem cell treatment each significantly increased not only CD25(+) cell frequency but also forkhead box p3 and IL-2Rα expression. Specifically, IL-10 was overexpressed after flagellin-preconditioned mesenchymal stem cell treatment. Analysis of collagen expression showed that the collagen type 1/collagen type 3 ratio, an indicator of wound-healing maturation, was low in the irradiated and mesenchymal stem cell-treated groups and returned to the normal level only after the flagellin-preconditioned mesenchymal stem cell treatment. This was associated with a reduction in myofibroblast accumulation. In a proctitis model, flagellin-preconditioned mesenchymal stem cells improved colonic immune capacity and enhanced tissue remodeling. © Society for Leukocyte Biology.

Epidermal stem cells: location, potential and contribution to cancer.

PubMed

Ambler, C A; Määttä, A

2009-01-01

Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

MicroRNAs: key regulators of stem cells.

PubMed

Gangaraju, Vamsi K; Lin, Haifan

2009-02-01

The hallmark of a stem cell is its ability to self-renew and to produce numerous differentiated cells. This unique property is controlled by dynamic interplays between extrinsic signalling, epigenetic, transcriptional and post-transcriptional regulations. Recent research indicates that microRNAs (miRNAs) have an important role in regulating stem cell self-renewal and differentiation by repressing the translation of selected mRNAs in stem cells and differentiating daughter cells. Such a role has been shown in embryonic stem cells, germline stem cells and various somatic tissue stem cells. These findings reveal a new dimension of gene regulation in controlling stem cell fate and behaviour.

[Progress in epidermal stem cells].

PubMed

Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

2010-03-01

Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

[Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

PubMed

Liang, Hang; Deng, Xiangyu; Shao, Zengwu

2017-10-01

To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

Amnion-derived stem cells: in quest of clinical applications

PubMed Central

2011-01-01

In the promising field of regenerative medicine, human perinatal stem cells are of great interest as potential stem cells with clinical applications. Perinatal stem cells could be isolated from normally discarded human placentae, which are an ideal cell source in terms of availability, the fewer number of ethical concerns, less DNA damage, and so on. Numerous studies have demonstrated that some of the placenta-derived cells possess stem cell characteristics like pluripotent differentiation ability, particularly in amniotic epithelial (AE) cells. Term human amniotic epithelium contains a relatively large number of stem cell marker-positive cells as an adult stem cell source. In this review, we introduce a model theory of why so many AE cells possess stem cell characteristics. We also describe previous work concerning the therapeutic applications and discuss the pluripotency of the AE cells and potential pitfalls for amnion-derived stem cell research. PMID:21596003

The role of stem cells in aesthetic surgery: fact or fiction?

PubMed

McArdle, Adrian; Senarath-Yapa, Kshemendra; Walmsley, Graham G; Hu, Michael; Atashroo, David A; Tevlin, Ruth; Zielins, Elizabeth; Gurtner, Geoffrey C; Wan, Derrick C; Longaker, Michael T

2014-08-01

Stem cells are attractive candidates for the development of novel therapies, targeting indications that involve functional restoration of defective tissue. Although most stem cell therapies are new and highly experimental, there are clinics around the world that exploit vulnerable patients with the hope of offering supposed stem cell therapies, many of which operate without credible scientific merit, oversight, or other patient protection. The authors review the potential and the drawbacks of incorporation of stem cells in cosmetic procedures. A review of U.S. Food and Drug Administration-approved indications and ongoing clinical trials with adipose stem cells is provided. Furthermore, a "snapshot" analysis of Web sites using the search terms "stem cell therapy" or "stem cell treatment" or "stem cell facelift" was performed. Despite the protective net cast by regulatory agencies such as the U.S. Food and Drug Administration and professional societies such as the American Society of Plastic Surgeons, the authors are witnessing worrying advertisements for procedures such as stem cell face lifts, stem cell breast augmentations, and even stem cell vaginal rejuvenation. The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence in the majority of cases. Stem cells offer tremendous potential, but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk. With plastic surgeons at the forefront of stem cell-based regenerative medicine, it is critically important that they provide an example of a rigorous approach to research, data collection, and advertising of stem cell therapies.

Polymer microarray technology for stem cell engineering

PubMed Central

Coyle, Robert; Jia, Jia; Mei, Ying

2015-01-01

Stem cells hold remarkable promise for applications in tissue engineering and disease modeling. During the past decade, significant progress has been made in developing soluble factors (e.g., small molecules and growth factors) to direct stem cells into a desired phenotype. However, the current lack of suitable synthetic materials to regulate stem cell activity has limited the realization of the enormous potential of stem cells. This can be attributed to a large number of materials properties (e.g., chemical structures and physical properties of materials) that can affect stem cell fate. This makes it challenging to design biomaterials to direct stem cell behavior. To address this, polymer microarray technology has been developed to rapidly identify materials for a variety of stem cell applications. In this article, we summarize recent developments in polymer array technology and their applications in stem cell engineering. Statement of significance Stem cells hold remarkable promise for applications in tissue engineering and disease modeling. In the last decade, significant progress has been made in developing chemically defined media to direct stem cells into a desired phenotype. However, the current lack of the suitable synthetic materials to regulate stem cell activities has been limiting the realization of the potential of stem cells. This can be attributed to the number of variables in material properties (e.g., chemical structures and physical properties) that can affect stem cells. Polymer microarray technology has shown to be a powerful tool to rapidly identify materials for a variety of stem cell applications. Here we summarize recent developments in polymer array technology and their applications in stem cell engineering. PMID:26497624

Stem cells in kidney regeneration.

PubMed

Yokote, Shinya; Yokoo, Takashi

2012-01-01

Currently many efforts are being made to apply regenerative medicine to kidney diseases using several types of stem/progenitor cells, such as mesenchymal stem cells, renal stem/progenitor cells, embryonic stem cells and induced pluripotent stem cells. Stem cells have the ability to repair injured organs and ameliorate damaged function. The strategy for kidney tissue repair is the recruitment of stem cells and soluble reparative factors to the kidney to elicit tissue repair and the induction of dedifferentiation of resident renal cells. On the other hand, where renal structure is totally disrupted, absolute kidney organ regeneration is needed to rebuild a whole functional kidney. In this review, we describe current advances in stem cell research for kidney tissue repair and de novo organ regeneration.

Stem Cell Sciences plc.

PubMed

Daniels, Sebnem

2006-09-01

Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

Modulation of Human Allogeneic and Syngeneic Pluripotent Stem Cells and Immunological Implications for Transplantation

PubMed Central

Sackett, S.D.; Brown, M.E.; Tremmel, D.M.; Ellis, T.; Burlingham, W.J.; Odorico, J.S.

2016-01-01

Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. PMID:26970668

Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

PubMed

Sackett, S D; Brown, M E; Tremmel, D M; Ellis, T; Burlingham, W J; Odorico, J S

2016-04-01

Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

Screening for intermediate and severe forms of thalassaemia in discarded red blood cells: optimization and feasibility.

PubMed

George, Elizabeth; Lai, Mei I; Teh, Lai Kuan; Ramasamy, Rajesh; Goh, Ern Huei; Asokan, Kamalan; Tan, J A M A; Vasudevan, Maithili; Low, Sharon

2011-12-01

Detection and quantification of Hb subtypes of human blood is integral to presumptive identification of thalassaemias. It has been used in neonatal screening of thalassaemia and Hb variants. The use of discarded red blood cells following processing of the cord blood for stem cells provides readily available diagnostic material for thalassaemia screening. In this study, we determined the range of Hb subtypes in 195 consecutive cord blood samples collected for cord blood banking. The 'cord blood samples' analysed were those of the remaining red blood cells after the cord blood was processed for stem cell storage. Quantification of Hb subtypes by high performance liquid chromatography (HPLC) was done on BioRad Variant II Hb testing system. Only 73 (36.5%) of the samples could be analyzed neat without dilution. With a 1:300 dilution with wash solution the acceptable area as recommended by the manufacturer for reading of a C-gram within the 1 to 3 million ranges were achieved in all. Eighteen (9%) 12 showed classical Hb Barts (y4) prerun peaks were confirmed by Sebia Hydrasys automated Hb gel electrophoresis and quantified by Sebia Capillarys 2 capillary electrophoresis. Only 1 (0.5%) was presumptively identified with HbH disease. Due to the limited number of samples no beta-thalassaemia major, Hb E beta-thalassaemia and Hb Barts hydrops fetalis were found. The HPLC assay was possible at a cost US$ 5 per sample and a turnover time of 10 samples per hour without technical difficulties. This study reports an effective and valuable protocol for thalassaemia screening in red blood cells which would otherwise be discarded during cord blood processing. Cord blood with severe and intermediate forms of thalassaemia can be preselected and not stored.

Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

PubMed

Goh, Felicia; Duhig, Edwina E; Clarke, Belinda E; McCaul, Elizabeth; Passmore, Linda; Courtney, Deborah; Windsor, Morgan; Naidoo, Rishendren; Franz, Louise; Parsonson, Kylie; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

2017-10-01

Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells.

PubMed

Wang, Ran; Chen, Shuxun; Li, Changxian; Ng, Kevin Tak Pan; Kong, Chi-wing; Cheng, Jinping; Cheng, Shuk Han; Li, Ronald A; Lo, Chung Mau; Man, Kwan; Sun, Dong

2016-02-04

Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. We employed laser-induced single-cell fusion technique to fuse the hepatocellular carcinoma cells and human embryonic stem cells (hESC). Real-time RT-PCR, flow cytometry and in vivo tumorigenicity assay were adopted to identify the gene expression difference. We successfully produced a fused cell line that coalesces the gene expression information of hepatocellular carcinoma cells and stem cells. Experimental results showed that the fused cells expressed cancer and stemness markers as well as exhibited increased resistance to drug treatment and enhanced tumorigenesis. Fusion with stem cells transforms liver cancer cells into tumor initiating-like cells. Results indicate that fusion between cancer cell and stem cell may generate tumor initiating-like cells.

Stem cell-derived vascular endothelial cells and their potential application in regenerative medicine

USDA-ARS?s Scientific Manuscript database

Although a 'vascular stem cell' population has not been identified or generated, vascular endothelial and mural cells (smooth muscle cells and pericytes) can be derived from currently known pluripotent stem cell sources, including human embryonic stem cells and induced pluripotent stem cells. We rev...

Efficient Direct Reprogramming of Mature Amniotic Cells into Endothelial Cells by ETS Factors and TGFβ Suppression

PubMed Central

Ginsberg, Michael; James, Daylon; Ding, Bi-Sen; Nolan, Daniel; Geng, Fuqiang; Butler, Jason M; Schachterle, William; Pulijaal, Venkat R; Mathew, Susan; Chasen, Stephen T; Xiang, Jenny; Rosenwaks, Zev; Shido, Koji; Elemento, Olivier; Rabbany, Sina Y; Rafii, Shahin

2012-01-01

ETS transcription factors ETV2, FLI1 and ERG1 specify pluripotent stem cells into endothelial cells (ECs). However, these ECs are unstable and drift towards non-vascular cell fates. We show that human mid-gestation c-Kit− lineage-committed amniotic cells (ACs) can be readily reprogrammed into induced vascular endothelial cells (iVECs). Transient ETV2 expression in ACs generated proliferative but immature iVECs, while co-expression with FLI1/ERG1 endowed iVECs with a vascular repertoire and morphology matching mature stable ECs. Brief TGFβ-inhibition functionalized VEGFR2 signaling, augmenting specification of ACs to iVECs. Genome-wide transcriptional analyses showed that iVECs are similar to adult ECs in which vascular-specific genes are turned on and non-vascular genes are silenced. Functionally, iVECs form long-lasting patent vasculature in Matrigel plugs and regenerating livers. Thus, short-term ETV2 expression and TGFβ-inhibition along with constitutive ERG1/FLI1 co-expression reprogram mature ACs into durable and functional iVECs with clinical-scale expansion potential. Public banking of HLA-typed iVECs would establish a vascular inventory for treatment of genetically diverse disorders. PMID:23084400

Hematopoietic cell differentiation from embryonic and induced pluripotent stem cells

PubMed Central

2013-01-01

Pluripotent stem cells, both embryonic stem cells and induced pluripotent stem cells, are undifferentiated cells that can self-renew and potentially differentiate into all hematopoietic lineages, such as hematopoietic stem cells (HSCs), hematopoietic progenitor cells and mature hematopoietic cells in the presence of a suitable culture system. Establishment of pluripotent stem cells provides a comprehensive model to study early hematopoietic development and has emerged as a powerful research tool to explore regenerative medicine. Nowadays, HSC transplantation and hematopoietic cell transfusion have successfully cured some patients, especially in malignant hematological diseases. Owing to a shortage of donors and a limited number of the cells, hematopoietic cell induction from pluripotent stem cells has been regarded as an alternative source of HSCs and mature hematopoietic cells for intended therapeutic purposes. Pluripotent stem cells are therefore extensively utilized to facilitate better understanding in hematopoietic development by recapitulating embryonic development in vivo, in which efficient strategies can be easily designed and deployed for the generation of hematopoietic lineages in vitro. We hereby review the current progress of hematopoietic cell induction from embryonic stem/induced pluripotent stem cells. PMID:23796405

Stem Cell Basics

MedlinePlus

... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

TOPICAL REVIEW: Stem cells engineering for cell-based therapy

NASA Astrophysics Data System (ADS)

Taupin, Philippe

2007-09-01

Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

PubMed

Tao, Ya-Chao; Wang, Meng-Lan; Chen, En-Qiang; Tang, Hong

2018-02-23

Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recent Progress in Stem Cell Modification for Cardiac Regeneration

PubMed Central

Voronina, Natalia; Steinhoff, Gustav

2018-01-01

During the past decades, stem cell-based therapy has acquired a promising role in regenerative medicine. The application of novel cell therapeutics for the treatment of cardiovascular diseases could potentially achieve the ambitious aim of effective cardiac regeneration. Despite the highly positive results from preclinical studies, data from phase I/II clinical trials are inconsistent and the improvement of cardiac remodeling and heart performance was found to be quite limited. The major issues which cardiac stem cell therapy is facing include inefficient cell delivery to the site of injury, accompanied by low cell retention and weak effectiveness of remaining stem cells in tissue regeneration. According to preclinical and clinical studies, various stem cells (adult stem cells, embryonic stem cells, and induced pluripotent stem cells) represent the most promising cell types so far. Beside the selection of the appropriate cell type, researchers have developed several strategies to produce “second-generation” stem cell products with improved regenerative capacity. Genetic and nongenetic modifications, chemical and physical preconditioning, and the application of biomaterials were found to significantly enhance the regenerative capacity of transplanted stem cells. In this review, we will give an overview of the recent developments in stem cell engineering with the goal to facilitate stem cell delivery and to promote their cardiac regenerative activity. PMID:29535769

Eat, breathe, ROS: controlling stem cell fate through metabolism.

PubMed

Kubli, Dieter A; Sussman, Mark A

2017-05-01

Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes.

Eat, breathe, ROS: controlling stem cell fate through metabolism

PubMed Central

Kubli, Dieter A.; Sussman, Mark A.

2017-01-01

Introduction Research reveals cardiac regeneration exists at levels previously deemed unattainable. Clinical trials using stem cells demonstrate promising cardiomyogenic and regenerative potential but insufficient contractile recovery. Incomplete understanding of the biology of administered cells likely contributes to inconsistent patient outcomes. Metabolism is a core component of many well-characterized stem cell types, and metabolic changes fundamentally alter stem cell fate from self-renewal to lineage commitment, and vice versa. However, the metabolism of stem cells currently studied for cardiac regeneration remains incompletely understood. Areas covered Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement. Expert commentary The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes. PMID:28406333

Therapeutic strategies involving uterine stem cells in reproductive medicine.

PubMed

Simoni, Michael; Taylor, Hugh S

2018-06-01

The current review provides an update on recent advances in stem cell biology relevant to female reproduction. Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted. Recruitment of stem cells from outside of the uterus occurs in setting of increased demand such as ischemia or injury. Bone marrow-derived multipotent stem cells are recruited to the uterus by estrogen or injury-induced expression of the chemokine CXCL12. In the setting of overwhelming injury, especially in the setting of low estrogen levels, there may be insufficient stem cell recruitment to adequately repair the uterus resulting in conditions such as Asherman syndrome or other endometrial defects. In contrast, excessive recruitment of stem cells underlies endometriosis. Enhanced understanding of stem-cell mobilization, recruitment, and engraftment has created the possibility of improved therapy for endometrial defects and endometriosis through enhanced manipulation of stem-cell trafficking. Further, the normal endometrium is a rich source of multipotent stem cells that can be used for numerous applications in regenerative medicine beyond reproduction. A better understanding of reproductive stem-cell biology may allow improved treatment of endometrial disease such as Asherman syndrome and other endometrial receptivity defects. Inhibiting stem-cell mobilization may also be helpful in endometriosis therapy. Finally, endometrial derived multipotent stem cells may play a crucial role in cell therapy for regenerative medicine.

Umbilical cord blood for unrelated bone marrow replacement; Asia bank and Japan cord blood bank network update.

PubMed

Mugishima, Hideo; Takahashi, Tuneo; Nagamura, Tokiko; Asano, Sigetaka; Saito, Hidehiko

2002-08-01

Cord blood offers many advantages including a high concentration of hematopoietic stem cells, a large number of potential donors, and ease of harvest. Furthermore, since there is no risk for either the mother or baby, few people refuse to donate. There is thought to be a low risk for virus contamination and also probably a low incidence and severity of GVHD. Cord blood can be obtained quickly without the assistance of a coordinator and one or 2 locus-mismatched HLA is usually acceptable. In Japan, there are 10 cord blood banks supported by the government. Between 1996 and June 2002, 9,500 units were registered with the Japan cord blood bank network (JCBBN). 630 units were delivered and most of these were transplanted. The status of registered cord blood units worldwide is shown. 59,081 units have been registered by NETCORD. The Japan cord blood bank network accounts for 13% of these units. I will discuss the Tokyo cord blood tank (TCBB). The bank at Tokyo, to which we belong, is one of the largest banks in Japan. We helped to establish Asia CORD in 2000 and have held annual conferences and meetings in Tokyo to exchange information. So far, China, Korea, Taiwan, Thailand, Viet Nam and Japan have participated. We accepted three trainees from the Ho Chi Minh City Blood Transfusion and Hematology Center for training in cord blood transplantation in May 2001. In January 2002, a patient with ALL received cord blood and was successfully engrafted at Ho Chi Minh City Blood Transfusion and Hematology Center. We present here the clinical outcome of these patients through Tokyo cord blood bank and Japan cord blood bank network. First, the number of CB units stored and registered at JCBBN and TCBB has increased rapidly over the past two years. Second, the survival rate of acute leukemia patients in release was significantly lower than that in patients in CR. Third, the engraftment rate in patients with metabolic disease (50%) was lower than that in patients with leukemia. Fourth, there was no significant difference in the incidence of acute GVHD greater than grade II between patients with a 1-locus and 2-locus mismatch. Finally, the incidence of acute GVHD was relatively low, and there were no deaths related to acute GVHD.

Gene screening of Wharton's jelly derived stem cells.

PubMed

Mechiche Alami, S; Velard, F; Draux, F; Siu Paredes, F; Josse, J; Lemaire, F; Gangloff, S C; Graesslin, O; Laurent-Maquin, D; Kerdjoudj, H

2014-01-01

Stem cells are the most powerful candidate for the treatment of various diseases. Suitable stem cell source should be harvested with minimal invasive procedure, found in great quantity, and transplanted with no risk of immune response and tumor formation. Fetal derived stem cells have been introduced as an excellent alternative to adult and embryonic stem cells use, but unfortunately, their degree of "stemness" and molecular characterization is still unclear. Several studies have been performed deciphering whether fetal stem cells meet the needs of regenerative medicine. We believe that a transcriptomic screening of Wharton's jelly stem cells will bring insights on cell population features.

Impact of delayed umbilical cord clamping on public cord blood donations: can we help future patients and benefit infant donors?

PubMed

Ciubotariu, Rodica; Scaradavou, Andromachi; Ciubotariu, Ilinca; Tarnawski, Michal; Lloyd, Sara; Albano, Maria; Dobrila, Ludy; Rubinstein, Pablo; Grunebaum, Amos

2018-03-25

Cord blood (CB) is a widely accepted stem cell source and its clinical utilization depends, to a great extent, on its cell content. Birth-to-clamping (BTC) time of umbilical cord determines placental transfusion to the newborn, and the remaining blood that can be collected and banked. The 2017 Committee Opinion of the American College of Obstetrics and Gynecologists (ACOG) recommends a delay of "at least 30-60 seconds" before clamping the cord for all newborns to ensure adequate iron stores. The impact of delayed cord clamping (DCC) on public CB banking can be substantial. Cord blood units (CBUs) collected from 1210 mothers at one hospital were evaluated for total nucleated cells (TNCs) and weight/volume based on time to clamping. Bank staff recorded BTC time in seconds as reported by obstetricians; collections were performed ex utero. Immediate clamping was defined as BTC of less than 30 seconds, whereas DCC was defined as BTC of 30 seconds or more. Cord clamping was immediate in 903 (75%) and delayed in 307 (25%) deliveries. Successful recovery (% clinical CBUs) decreased 10-fold with DCC of more than 60 seconds (22% vs. 2.4%, p < 0.001). CBUs collected after DCC of more than 60 seconds had significantly lower TNC counts than those after DCC of less than 60 seconds (p < 0.0001). Furthermore, 38% to 46% of CBUs after DCC of more than 60 seconds had volume of less than 40 mL. Our study indicates that DCC of 30 to 60 seconds has a small negative impact on collection of high-TNC-count CBUs. However, increasing BTC to more than 60 seconds decreases significantly both TNC content and volume, reducing drastically the chances of obtaining clinically useful CBUs. © 2018 AABB.

Nine Things to Know About Stem Cell Treatments

MedlinePlus

... Toggle Nav Nine Things To Know About Stem Cell Treatments Home > Stem Cells and Medicine > Nine Things ... About Stem Cell Treatments Many clinics offering stem cell treatments make claims that are not supported by ...

Cancer (stem) cell differentiation: An inherent or acquired property?

PubMed

Mohr, Marieke; Zänker, Kurt S; Dittmar, Thomas

2015-12-01

There is a growing list of data indicating that cancer (stem) cells could functionally adapt foreign tissue features, such as endothelial-like cells or neuroendocrine cells, express lineage markers or could differentiate into various lineages in response to appropriate differentiation criteria. The finding that cancer (stem) cells may possess some kind of differentiation capacity poses the question whether this might be an inherent or acquired property. Cancer stem cells share stem cell characteristics and may thus possess an inherent differentiation capacity enabling the cells to respond to various differentiation stimuli. Considering the plasticity of cancer (stem) cells, even non-tumorigenic (and putatively non-differentiable) tumor cells could give rise to tumorigenic tumor stem cells, exhibiting stem cell characteristics including an inherent differentiation capacity. On the contrary, cancer (stem) cells may have acquired differentiation capacity as a consequence of a previous cell fusion event with cell types exhibiting differentiation potential and being fusogenic, such as macrophages or stem cells. Of pivotal interest in a tumor context are macrophages, which chiefly foster the chronically inflamed tumor microenvironment. Because chronically inflamed tissue is a well-known trigger for cell fusion and both macrophages and stem cells are highly fusogenic we conclude that cell fusion events between these cell types and cancer (stem) cells should frequently occur, thereby giving rise to hybrid cells exhibiting not only novel properties, like an enhanced metastatogenic phenotype, but also parental characteristics, such as differentiation capacity. Conceivably, the combination of both properties might be advantageous for metastasizing cancer (stem) cells to adapt better and faster to a foreign organ tissue environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sox10+ adult stem cells contribute to biomaterial encapsulation and microvascularization

PubMed Central

Wang, Dong; Wang, Aijun; Wu, Fan; Qiu, Xuefeng; Li, Ye; Chu, Julia; Huang, Wen-Chin; Xu, Kang; Gong, Xiaohua; Li, Song

2017-01-01

Implanted biomaterials and biomedical devices generally induce foreign body reaction and end up with encapsulation by a dense avascular fibrous layer enriched in extracellular matrix. Fibroblasts/myofibroblasts are thought to be the major cell type involved in encapsulation, but it is unclear whether and how stem cells contribute to this process. Here we show, for the first time, that Sox10+ adult stem cells contribute to both encapsulation and microvessel formation. Sox10+ adult stem cells were found sparsely in the stroma of subcutaneous loose connective tissues. Upon subcutaneous biomaterial implantation, Sox10+ stem cells were activated and recruited to the biomaterial scaffold, and differentiated into fibroblasts and then myofibroblasts. This differentiation process from Sox10+ stem cells to myofibroblasts could be recapitulated in vitro. On the other hand, Sox10+ stem cells could differentiate into perivascular cells to stabilize newly formed microvessels. Sox10+ stem cells and endothelial cells in three-dimensional co-culture self-assembled into microvessels, and platelet-derived growth factor had chemotactic effect on Sox10+ stem cells. Transplanted Sox10+ stem cells differentiated into smooth muscle cells to stabilize functional microvessels. These findings demonstrate the critical role of adult stem cells in tissue remodeling and unravel the complexity of stem cell fate determination. PMID:28071739

Tumor suppressors Sav/Scrib and oncogene Ras regulate stem cell transformation in adult Drosophila Malpighian Tubules

PubMed Central

Zeng, Xiankun; Singh, Shree Ram; Hou, David; Hou, Steven X.

2012-01-01

An increasing body of evidence suggests that tumors might originate from a few transformed cells that share many properties with normal stem cells. However, it remains unclear how normal stem cells are transformed into cancer stem cells. Here, we demonstrated that mutations causing the loss of tumor suppressor Sav or Scrib or activation of the oncogene Ras transform normal stem cells into cancer stem cells through a multistep process in the adult Drosophila Malpighian Tubules (MTs). In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, in flies with loss-of-function sav or scrib or gain-of-function Ras mutations, both daughter cells grew and behaved like stem cells, leading to the formation of tumors in MTs. Ras functioned downstream of Sav and Scrib in regulating the stem cell transformation. The Ras-transformed stem cells exhibited many of the hallmarks of cancer, such as increased proliferation, reduced cell death, and failure to differentiate. We further demonstrated that several signal transduction pathways (including MEK/MAPK, RhoA, PKA, and TOR) mediate Rasṕ function in the stem cell transformation. Therefore, we have identified a molecular mechanism that regulates stem cell transformation, and this finding may lead to strategies for preventing tumor formation in certain organs. PMID:20432470

The king is dead, long live the king: entering a new era of stem cell research and clinical development.

PubMed

Ichim, Thomas; Riordan, Neil H; Stroncek, David F

2011-12-20

In mid November the biopharma industry was shocked by the announcement from Geron that they were ending work on embryonic stem cell research and therapy. For more than 10 years the public image of all stem cell research has been equated with embryonic stem cells. Unfortunately, a fundamentally important medical and financial fact was being ignored: embryonic stem cell therapy is extremely immature. In parallel to efforts in embryonic stem cell research and development, scientists and physicians in the field of adult stem cells realized that the natural role of adult stem cells in the body is to promote healing and to act like endogenous "repair cells" and, as a result, numerous companies have entered the field of adult stem cell therapy with the goal of expanding numbers of adult stem cells for administration to patients with various conditions. In contrast to embryonic stem cells, which are extremely expensive and potentially dangerous, adult cell cells are inexpensive and have an excellent safety record when used in humans. Many studies are now showing that adult stem cells are practical, patient-applicable, therapeutics that are very close to being available for incorporation into the practice of medicine. These events signal the entrance of the field of stem cells into a new era: an era where hype and misinformation no longer triumph over economic and medical realities.

Control of stem cell fate by engineering their micro and nanoenvironment

PubMed Central

Griffin, Michelle F; Butler, Peter E; Seifalian, Alexander M; Kalaskar, Deepak M

2015-01-01

Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix (ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine. PMID:25621104

The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering

PubMed Central

Ratajczak, Jessica; Bronckaers, Annelies; Dillen, Yörg; Gervois, Pascal; Vangansewinkel, Tim; Driesen, Ronald B.; Wolfs, Esther; Lambrichts, Ivo

2016-01-01

Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair. PMID:27688777

Multipotent Stem Cell and Reproduction.

PubMed

Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sobhani, Aligholi

Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. The accessibility and adaptability of these amazing cells create them a great therapeutic choice for different part of medical approaches, and it becomes interesting topic in the scientific researches to found obvious method for the most advantageous use of MSC-based therapies. Recent studies in the field of stem cell biology have provided new perspectives and opportunities for the treatment of infertility disorders.

Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

PubMed

Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

2015-01-01

Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

ERIC Educational Resources Information Center

Concannon, James P.; Siegel, Marcelle A.; Halverson, Kristy; Freyermuth, Sharyn

2010-01-01

In this study, we examined 96 undergraduate non-science majors' conceptions of stem cells, stem cell research, and cloning. This study was performed at a large, Midwest, research extensive university. Participants in the study were asked to answer 23 questions relating to stem cells, stem cell research, and cloning in an on-line assessment before…

Muscle Stem Cells: A Model System for Adult Stem Cell Biology.

PubMed

Cornelison, Ddw; Perdiguero, Eusebio

2017-01-01

Skeletal muscle stem cells, originally termed satellite cells for their position adjacent to differentiated muscle fibers, are absolutely required for the process of skeletal muscle repair and regeneration. In the last decade, satellite cells have become one of the most studied adult stem cell systems and have emerged as a standard model not only in the field of stem cell-driven tissue regeneration but also in stem cell dysfunction and aging. Here, we provide background in the field and discuss recent advances in our understanding of muscle stem cell function and dysfunction, particularly in the case of aging, and the potential involvement of muscle stem cells in genetic diseases such as the muscular dystrophies.

Battery Charge Equalizer with Transformer Array

NASA Technical Reports Server (NTRS)

Davies, Francis

2013-01-01

High-power batteries generally consist of a series connection of many cells or cell banks. In order to maintain high performance over battery life, it is desirable to keep the state of charge of all the cell banks equal. A method provides individual charging for battery cells in a large, high-voltage battery array with a minimum number of transformers while maintaining reasonable efficiency. This is designed to augment a simple highcurrent charger that supplies the main charge energy. The innovation will form part of a larger battery charge system. It consists of a transformer array connected to the battery array through rectification and filtering circuits. The transformer array is connected to a drive circuit and a timing and control circuit that allow individual battery cells or cell banks to be charged. The timing circuit and control circuit connect to a charge controller that uses battery instrumentation to determine which battery bank to charge. It is important to note that the innovation can charge an individual cell bank at the same time that the main battery charger is charging the high-voltage battery. The fact that the battery cell banks are at a non-zero voltage, and that they are all at similar voltages, can be used to allow charging of individual cell banks. A set of transformers can be connected with secondary windings in series to make weighted sums of the voltages on the primaries.

Redox regulation of plant stem cell fate.

PubMed

Zeng, Jian; Dong, Zhicheng; Wu, Haijun; Tian, Zhaoxia; Zhao, Zhong

2017-10-02

Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H 2 O 2 ) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS-metabolizing enzymes. The superoxide anion (O2·-) is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H 2 O 2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H 2 O 2 negatively regulates O2·- biosynthesis in stem cells, and increasing H 2 O 2 levels or scavenging O2·- leads to the termination of stem cells. Our results provide a mechanistic framework for ROS-mediated control of plant stem cell fate and demonstrate that the balance between O2·- and H 2 O 2 is key to stem cell maintenance and differentiation. © 2017 The Authors.

Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium

PubMed Central

Ouyang, Hong; Goldberg, Jeffrey L.; Chen, Shuyi; Li, Wei; Xu, Guo-Tong; Li, Wei; Zhang, Kang; Nussenblatt, Robert B.; Liu, Yizhi; Xie, Ting; Chan, Chi-Chao; Zack, Donald J.

2016-01-01

Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide. Recent results on the clinical trial of retinal pigment epithelial (RPE) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in treating dry AMD and Stargardt’s disease in the US, Japan, England, and China have generated great excitement and hope. This marks the beginning of the ocular stem cell therapy era. The recent Zhongshan Ophthalmic Center Ocular Stem Cell Symposium discussed the potential applications of various stem cell types in stem cell-based therapies, drug discoveries and tissue engineering for treating ocular diseases. PMID:27102165

StemTextSearch: Stem cell gene database with evidence from abstracts.

PubMed

Chen, Chou-Cheng; Ho, Chung-Liang

2017-05-01

Previous studies have used many methods to find biomarkers in stem cells, including text mining, experimental data and image storage. However, no text-mining methods have yet been developed which can identify whether a gene plays a positive or negative role in stem cells. StemTextSearch identifies the role of a gene in stem cells by using a text-mining method to find combinations of gene regulation, stem-cell regulation and cell processes in the same sentences of biomedical abstracts. The dataset includes 5797 genes, with 1534 genes having positive roles in stem cells, 1335 genes having negative roles, 1654 genes with both positive and negative roles, and 1274 with an uncertain role. The precision of gene role in StemTextSearch is 0.66, and the recall is 0.78. StemTextSearch is a web-based engine with queries that specify (i) gene, (ii) category of stem cell, (iii) gene role, (iv) gene regulation, (v) cell process, (vi) stem-cell regulation, and (vii) species. StemTextSearch is available through http://bio.yungyun.com.tw/StemTextSearch.aspx. Copyright © 2017. Published by Elsevier Inc.

Application of Stem Cell Technology in Dental Regenerative Medicine.

PubMed

Feng, Ruoxue; Lengner, Chistopher

2013-07-01

In this review, we summarize the current literature regarding the isolation and characterization of dental tissue-derived stem cells and address the potential of these cell types for use in regenerative cell transplantation therapy. Looking forward, platforms for the delivery of stem cells via scaffolds and the use of growth factors and cytokines for enhancing dental stem cell self-renewal and differentiation are discussed. We aim to understand the developmental origins of dental tissues in an effort to elucidate the molecular pathways governing the genesis of somatic dental stem cells. The advantages and disadvantages of several dental stem cells are discussed, including the developmental stage and specific locations from which these cells can be purified. In particular, stem cells from human exfoliated deciduous teeth may act as a very practical and easily accessibly reservoir for autologous stem cells and hold the most value in stem cell therapy. Dental pulp stem cells and periodontal ligament stem cells should also be considered for their triple lineage differentiation ability and relative ease of isolation. Further, we address the potentials and limitations of induced pluripotent stem cells as a cell source in dental regenerative. From an economical and a practical standpoint, dental stem cell therapy would be most easily applied in the prevention of periodontal ligament detachment and bone atrophy, as well as in the regeneration of dentin-pulp complex. In contrast, cell-based tooth replacement due to decay or other oral pathology seems, at the current time, an untenable approach.

Methods for Stem Cell Production and Therapy

NASA Technical Reports Server (NTRS)

Valluri, Jagan V. (Inventor); Claudio, Pier Paolo (Inventor)

2015-01-01

The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

Dental pulp stem cells in regenerative dentistry.

PubMed

Casagrande, Luciano; Cordeiro, Mabel M; Nör, Silvia A; Nör, Jacques E

2011-01-01

Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

Translating stem cell therapies: the role of companion animals in regenerative medicine

PubMed Central

Volk, Susan W.; Theoret, Christine

2013-01-01

Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell-based therapies involving hematopoietic (HSC) and mesenchymal stem cells (MSC) as well as other adult regenerative cells and recently embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC). In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the “One Health Initiative”, the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored. PMID:23627495

Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche

PubMed Central

2018-01-01

ABSTRACT Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In Drosophila ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or hid expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal. PMID:29361569

Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche.

PubMed

Wang, Xiaoxi; Page-McCaw, Andrea

2018-02-07

Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In Drosophila ovaries, germline stem cells depend on cap cells for self-renewing signals and physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or hid expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal. © 2018. Published by The Company of Biologists Ltd.

21st Nantes Actualités Transplantation: "When Stem Cells Meet Immunology".

PubMed

Anegon, Ignacio; Nguyen, Tuan Huy

2017-01-01

"When Stem Cells Meet Immunology" has been the topic of the 21st annual "Nantes Actualités en Transplantation" meeting (June 9-10, 2016, Nantes, France). This meeting brought together pioneers and leading experts in the fields of stem cells, biomaterials and immunoregulation. Presentations covered multipotent (mesenchymal and hematopoietic) and pluripotent stem cells (embryonic and induced) for regenerative medicine of incurable diseases, immunotherapy and blood transfusions. An additional focus had been immune rejections and responses of allogeneic or autologous stem cells. Conversely, stem cells are also able to directly modulate the immune response through the production of immunoregulatory molecules. Moreover, stem cells may also provide an unlimited source of immune cells (DCs, NK cells, B cells, and T cells) that can operate as "super" immune cells, for example, through genetic engineering with chimeric antigen receptors.This meeting report puts presentations into an overall context highlighting new potential biomarkers for potency prediction of mesenchymal stem cell-derived and pluripotent stem cell-derived multicellular organoids. Finally, we propose future directions arising from the flourishing encounter of stem cell and immune biology.

Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: implications for stem cell mitosis and centrosome dynamics.

PubMed

Mannino, Mariella; Gomez-Roman, Natividad; Hochegger, Helfrid; Chalmers, Anthony J

2014-07-01

Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell divisions. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of aging on stem cells

PubMed Central

Ahmed, Abu Shufian Ishtiaq; Sheng, Matilda HC; Wasnik, Samiksha; Baylink, David J; Lau, Kin-Hing William

2017-01-01

Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of aging-associated disorders, but also in future development of novel effective stem cell-based therapies to treat aging-associated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects. PMID:28261550

Engineering Stem Cells for Biomedical Applications

PubMed Central

Yin, Perry T.; Han, Edward

2018-01-01

Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer. PMID:25772134

Single-cell sequencing in stem cell biology.

PubMed

Wen, Lu; Tang, Fuchou

2016-04-15

Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

The Implications of the Cancer Stem Cell Hypothesis for Neuro-Oncology and Neurology.

PubMed

Rich, Jeremy N

2008-05-01

The cancer stem cell hypothesis posits that cancers contain a subset of neoplastic cells that propagate and maintain tumors through sustained self-renewal and potent tumorigenecity. Recent excitement has been generated by a number of reports that have demonstrated the existence of cancer stem cells in several types of brain tumors. Brain cancer stem cells - also called tumor initiating cells or tumor propagating cells - share features with normal neural stem cells but do not necessarily originate from stem cells. Although most cancers have only a small fraction of cancer stem cells, these tumor cells have been shown in laboratory studies to contribute to therapeutic resistance, formation of new blood vessels to supply the tumor, and tumor spread. As malignant brain tumors rank among the deadliest of all neurologic diseases, the identification of new cellular targets may have profound implications in neuro-oncology. Novel drugs that target stem cell pathways active in brain tumors have been efficacious against cancer stem cells suggesting that anti-cancer stem cell therapies may advance brain tumor therapy. The cancer stem cell hypothesis may have several implications for other neurologic diseases as caution must be exercised in activating stem cell maintenance pathways in cellular therapies for neurodegenerative diseases. The ability for a small fraction of cells to determine the overall course of a disease may also inform new paradigms of disease that may translate into improved patient outcomes.

Can bone marrow differentiate into renal cells?

PubMed

Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

[The emerging technology of tissue engineering : Focus on stem cell niche].

PubMed

Schlötzer-Schrehardt, U; Freudenberg, U; Kruse, F E

2017-04-01

Limbal stem cells reside in a highly specialized complex microenvironment that is known as the stem cell niche, an anatomically protected region at the bottom of the Palisades of Vogt, where the stem cells are located and where their quiescence, proliferation and differentiation are maintained in balance. Besides the epithelial stem and progenitor cell clusters, the limbal niche comprises several types of supporting niche cells and a specific extracellular matrix mediating biochemical and biophysical signals. Stem cell-based tissue engineering aims to mimic the native stem cell niche and to present appropriate microenvironmental cues in a controlled and reproducible fashion in order to maintain stem cell function within the graft. Current therapeutic approaches for ex vivo expansion of limbal stem cells only take advantage of surrogate niches. However, new insights into the molecular composition of the limbal niche and innovative biosynthetic scaffolds have stimulated novel strategies for niche-driven stem cell cultivation. Promising experimental approaches include collagen-based organotypic coculture systems of limbal epithelial stem cells with their niche cells and biomimetic hydrogel platforms prefunctionalized with appropriate biomolecular and biophysical signals. Future translation of these novel regenerative strategies into clinical application is expected to improve long-term outcomes of limbal stem cell transplantation for ocular surface reconstruction.

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

PubMed

Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

Application of Stem Cells in Oral Disease Therapy: Progresses and Perspectives

PubMed Central

Yang, Bo; Qiu, Yi; Zhou, Niu; Ouyang, Hong; Ding, Junjun; Cheng, Bin; Sun, Jianbo

2017-01-01

Stem cells are undifferentiated and pluripotent cells that can differentiate into specialized cells with a more specific function. Stem cell therapies become preferred methods for the treatment of multiple diseases. Oral and maxillofacial defect is one kind of the diseases that could be most possibly cured by stem cell therapies. Here we discussed oral diseases, oral adult stem cells, iPS cells, and the progresses/challenges/perspectives of application of stem cells for oral disease treatment. PMID:28421002

Diploid, but not haploid, human embryonic stem cells can be derived from microsurgically repaired tripronuclear human zygotes

PubMed Central

Fan, Yong; Li, Rong; Huang, Jin; Yu, Yang; Qiao, Jie

2013-01-01

Human embryonic stem cells have shown tremendous potential in regenerative medicine, and the recent progress in haploid embryonic stem cells provides new insights for future applications of embryonic stem cells. Disruption of normal fertilized embryos remains controversial; thus, the development of a new source for human embryonic stem cells is important for their usefulness. Here, we investigated the feasibility of haploid and diploid embryo reconstruction and embryonic stem cell derivation using microsurgically repaired tripronuclear human zygotes. Diploid and haploid zygotes were successfully reconstructed, but a large proportion of them still had a tripolar spindle assembly. The reconstructed embryos developed to the blastocyst stage, although the loss of chromosomes was observed in these zygotes. Finally, triploid and diploid human embryonic stem cells were derived from tripronuclear and reconstructed zygotes (from which only one pronucleus was removed), but haploid human embryonic stem cells were not successfully derived from the reconstructed zygotes when two pronuclei were removed. Both triploid and diploid human embryonic stem cells showed the general characteristics of human embryonic stem cells. These results indicate that the lower embryo quality resulting from abnormal spindle assembly contributed to the failure of the haploid embryonic stem cell derivation. However, the successful derivation of diploid embryonic stem cells demonstrated that microsurgical tripronuclear zygotes are an alternative source of human embryonic stem cells. In the future, improving spindle assembly will facilitate the application of triploid zygotes to the field of haploid embryonic stem cells. PMID:23255130

Nano scaffolds and stem cell therapy in liver tissue engineering

NASA Astrophysics Data System (ADS)

Montaser, Laila M.; Fawzy, Sherin M.

2015-08-01

Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

Stem-Cell-Based Tumorigenesis in Adult Drosophila.

PubMed

Hou, S X; Singh, S R

2017-01-01

Recent studies suggest that a small subset of cells within a tumor, the so-called cancer stem cells (CSCs), are responsible for tumor propagation, relapse, and the eventual death of most cancer patients. CSCs may derive from a few tumor-initiating cells, which are either transformed normal stem cells or reprogrammed differentiated cells after acquiring initial cancer-causing mutations. CSCs and normal stem cells share some properties, but CSCs differ from normal stem cells in their tumorigenic ability. Notably, CSCs are usually resistant to chemo- and radiation therapies. Despite the apparent roles of CSCs in human cancers, the biology underlying their behaviors remains poorly understood. Over the past few years, studies in Drosophila have significantly contributed to this new frontier of cancer research. Here, we first review how stem-cell tumors are initiated and propagated in Drosophila, through niche appropriation in the posterior midgut and through stem-cell competition for niche occupancy in the testis. We then discuss the differences between normal and tumorigenic stem cells, revealed by studying Ras V12 -transformed stem-cell tumors in the Drosophila kidney. Finally, we review the biology behind therapy resistance, which has been elucidated through studies of stem-cell resistance and sensitivity to death inducers using female germline stem cells and intestinal stem cells of the posterior midgut. We expect that screens using adult Drosophila neoplastic stem-cell tumor models will be valuable for identifying novel and effective compounds for treating human cancers. © 2017 Elsevier Inc. All rights reserved.

Stem cells with potential to generate insulin producing cells in man.

PubMed

Zulewski, Henryk

2006-10-14

Replacement of insulin-producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans--although successful in experienced centres--is limited by the lack of donor organs. Generation of insulin-producing cells from stem cells represents an attractive alternative. Stem cells with the potential to differentiate into insulin-producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, central nervous system, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns and the inability to create patient specific ESC with therapeutic cloning. Among adult stem cells mesenchymal stem cells appear to have a particular developmental plasticity ex vivo that include their ability to adopt a pancreatic endocrine phenotype. The present review summarises the current knowledge on the development of insulin-producing cells from stem cells with special emphasis on human mesenchymal stem cells isolated from the pancreas and adipose tissue.

Stem cells with potential to generate insulin-producing cells in man.

PubMed

Zulewski, Henryk

2007-03-02

Replacement of insulin-producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans--although successful in experienced centres--is limited by the lack of donor organs. Generation of insulin-producing cells from stem cells represents an attractive alternative. Stem cells with the potential to differentiate into insulin-producing cells include embryonic stem cells (ESC) as well as adult stem cells from various tissues including the pancreas, liver, central nervous system, bone marrow and adipose tissue. The use of human ESC is hampered by ethical concerns and the inability to create patient specific ESC with therapeutic cloning. Among adult stem cells mesenchymal stem cells appear to have a particular developmental plasticity ex vivo that include their ability to adopt a pancreatic endocrine phenotype. The present review summarises the current knowledge on the development of insulin-producing cells from stem cells with special emphasis on human mesenchymal stem cells isolated from the pancreas and adipose tissue.

Mechanical forces direct stem cell behaviour in development and regeneration

PubMed Central

Vining, Kyle H.; Mooney, David J.

2018-01-01

Stem cells and their local microenvironment, or niche, communicate through mechanical, cues to regulate cell fate and cell behaviour, and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their differentiation and self-renewal. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights on the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies. PMID:29115301

Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

PubMed Central

Becker, Silke; Jayaram, Hari; Limb, G. Astrid

2012-01-01

Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice. PMID:24710533

New insights into mechanisms of stem cell daughter fate determination in regenerative tissues.

PubMed

Sada, Aiko; Tumbar, Tudorita

2013-01-01

Stem cells can self-renew and differentiate over extended periods of time. Understanding how stem cells acquire their fates is a central question in stem cell biology. Early work in Drosophila germ line and neuroblast showed that fate choice is achieved by strict asymmetric divisions that can generate each time one stem and one differentiated cell. More recent work suggests that during homeostasis, some stem cells can divide symmetrically to generate two differentiated cells or two identical stem cells to compensate for stem cell loss that occurred by direct differentiation or apoptosis. The interplay of all these factors ensures constant tissue regeneration and the maintenance of stem cell pool size. This interplay can be modeled as a population-deterministic dynamics that, at least in some systems, may be described as stochastic behavior. Here, we overview recent progress made on the characterization of stem cell dynamics in regenerative tissues. Copyright © 2013 Elsevier Inc. All rights reserved.

Extinction models for cancer stem cell therapy

PubMed Central

Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

2012-01-01

Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives. PMID:22001354

Extinction models for cancer stem cell therapy.

PubMed

Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S; Lange, Kenneth L

2011-12-01

Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth-death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives. Copyright © 2011 Elsevier Inc. All rights reserved.

Cryopreservation and Revival of Human Mesenchymal Stromal Cells.

PubMed

Haack-Sørensen, Mandana; Ekblond, Annette; Kastrup, Jens

2016-01-01

Cell-based therapy is a promising and innovative new treatment for different degenerative and autoimmune diseases, and mesenchymal stromal cells (MSCs) from the bone marrow have demonstrated great therapeutic potential due to their immunosuppressive and regenerative capacities.The establishment of methods for large-scale expansion of clinical-grade MSCs in vitro has paved the way for their therapeutic use in clinical trials. However, the clinical application of MSCs also requires cryopreservation and banking of the cell products. To preserve autologous or allogeneic MSCs for future clinical applications, a reliable and effective cryopreservation method is required.Developing a successful cryopreservation protocol for clinical stem cell products, cryopreservation media, cryoprotectant agents (CPAs), the freezing container, the freezing temperature, and the cooling and warming rate are all aspects which should be considered.A major challenge is the selection of a suitable cryoprotectant which is able to penetrate the cells and yet has low toxicity.This chapter focuses on recent technological developments relevant for the cryopreservation of MSCs using the most commonly used cryopreservation medium containing DMSO and animal serum or human-derived products for research use and the animal protein-free cryopreservation media CryoStor (BioLife Solutions) for clinical use.

Optimal method for collection of umbilical cord blood: an Egyptian trial for a public cord blood bank.

PubMed

Bassiouny, M R; El-Chennawi, F; Mansour, A K; Yahia, S; Darwish, A

2015-06-01

Umbilical cord blood (UCB) contains stem cells and can be used as an alternative to bone marrow transplantation. Engraftment is dependent on the total nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study was designed to evaluate the effect of the method of collection of the UCB on the yield of the cord blood units. Informed consent was obtained from 100 eligible mothers for donation of cord blood. Both in utero and ex utero methods were used for collection. The cord blood volume was measured. The TNC and the CD34+ cell counts were enumerated. We have found that in utero collection gave significantly larger volumes of cord blood and higher TNC counts than ex utero collection. There was no significant difference between both methods regarding the CD34+ cell counts. This study revealed a significant correlation between the volume of the collected cord blood and both TNC and CD34+ cell counts. It is better to collect cord blood in utero before placental delivery to optimize the quality of the cord blood unit. © 2015 AABB.

Natural Killer Cells for Therapy of Leukemia

PubMed Central

Suck, Garnet; Linn, Yeh Ching; Tonn, Torsten

2016-01-01

Summary Clinical application of natural killer (NK) cells against leukemia is an area of intense investigation. In human leukocyte antigen-mismatched allogeneic hematopoietic stem cell transplantations (HSCT), alloreactive NK cells exert powerful anti-leukemic activity in preventing relapse in the absence of graft-versus-host disease, particularly in acute myeloid leukemia patients. Adoptive transfer of donor NK cells post-HSCT or in non-transplant scenarios may be superior to the currently widely used unmanipulated donor lymphocyte infusion. This concept could be further improved through transfusion of activated NK cells. Significant progress has been made in good manufacturing practice (GMP)-compliant large-scale production of stimulated effectors. However, inherent limitations remain. These include differing yields and compositions of the end-product due to donor variability and inefficient means for cryopreservation. Moreover, the impact of the various novel activation strategies on NK cell biology and in vivo behavior are barely understood. In contrast, reproduction of the third-party NK-92 drug from a cryostored GMP-compliant master cell bank is straightforward and efficient. Safety for the application of this highly cytotoxic cell line was demonstrated in first clinical trials. This novel ‘off-the-shelf’ product could become a treatment option for a broad patient population. For specific tumor targeting chimeric-antigen-receptor-engineered NK-92 cells have been designed. PMID:27226791

Aging and stem cell therapy: AMPK as an applicable pharmacological target for rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy.

PubMed

Khorraminejad-Shirazi, Mohammadhossein; Farahmandnia, Mohammad; Kardeh, Bahareh; Estedlal, Alireza; Kardeh, Sina; Monabati, Ahmad

2017-10-19

In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy. By utilizing an effective therapeutic intervention for aged stem cells, stem cell therapy can become more promising for future application. mTORC1 inhibition is a practical approach to preserve the stem cell pool. In this article, we review the dynamic interaction between sirtuin (silent mating type information regulation 2 homolog) 1, AMPK, and mTORC1. We propose that using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide, A769662, metformin, and oxidized nicotinamide adenine dinucleotide (NAD + ) are practical ways to be employed for achieving better optimized results in stem cell-based transplantation therapies. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Stemness of spermatogonial stem cells encapsulated in alginate hydrogel during cryopreservation.

PubMed

Pirnia, A; Parivar, K; Hemadi, M; Yaghmaei, P; Gholami, M

2017-06-01

This study investigated the effect of spermatogonial stem cell encapsulated in alginate hydrogel during cryopreservation, as cells were protected against damage during cryopreservation within the hydrogel. Spermatogonial stem cells were isolated from the testes of Balb/c mice pups (6 days old), purified in laminin-coated dishes and CD90.1 microbeads, encapsulated in alginate hydrogel and then cryopreserved. After thawing, cell viability and Spermatogonial stem cell (SSC) colony diameter were evaluated. After RNA was isolated and cDNA was synthesised, the expression of stemness genes was considered using RT real-time PCR. Finally, spermatogonial stem cells labelled with BrdU were transplanted to busulfan azoospermic mouse models. Lin28a and Sall4 genes were significantly upregulated after cryopreservation in alginate hydrogel. However, cell viability was significantly decreased. The diameter of colonies consisting of spermatogonial stem cells freeze-thawed in alginate microbeads showed no significant difference with fresh spermatogonial stem cells and the control group. The injection of freeze-thawed spermatogonial stem cells encapsulated in alginate hydrogel resulted in spermatogenesis recovery. Alginate mimics the extracellular matrices (ECM) for spermatogonial stem cells; therefore, it can support stemness potential during the cell cryopreservation process and restart spermatogenesis after transplantation. © 2016 Blackwell Verlag GmbH.

Normal and cancer mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR Axis

PubMed Central

Celià-Terrassa, Toni; Liu, Daniel; Choudhury, Abrar; Hang, Xiang; Wei, Yong; Zamalloa, Jose; Alfaro-Aco, Raymundo; Chakrabarti, Rumela; Jiang, Yi-Zhou; Koh, Bong Ihn; Smith, Heath; DeCoste, Christina; Li, Jun-Jing; Shao, Zhi-Ming; Kang, Yibin

2017-01-01

Tumor-initiating cells (TICs), or cancer stem cells (CSC), possess stem cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells (MaSCs) and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by epithelial and immune cells in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER− breast tumors, functionally promotes tumor initiation and metastasis, and is associated with poor clinical outcome. Our study therefore reveals a common mechanism shared by normal and malignant stem cells to protect them from suppressive immune cytokine signaling. PMID:28530657

The Role of Epithelial-Mesenchymal Transition in the Formation of Normal and Neoplastic Mammary Epithelial Stem Cells

DTIC Science & Technology

2011-09-01

separating stem cell and non- stem cell populations of normal and breast cancer cells and identified EMT transcription factors most likely involved in... stem cell biology. Preliminary results directly demonstrate that transient induction of EMT increases the number of mammary epithelial stem cells...EMT and entrance into a stem - cell state. The outcome of these experiments holds important implications for the mechanisms controlling the formation of

Role of the Stem Cell Niche in Hormone-Induced Tumorigenesis in Fetal Mouse Mammary Epithelium

DTIC Science & Technology

2005-08-01

responsive, self renewing and pluripotent. A structure specialized to contain and regulate stem cell activity has been structurally and molecularly...described in Drosophila and some mammalian tissues. The structure, the stem cell niche, functions to 1) shield the stem cell from the burden of incoming...directing stem cell renewal and maturation, 3) prevent stem cells from wandering through the tissue and producing new cells inappropriately, 4) prevent

The Effect of Laser Irradiation on Adipose Derived Stem Cell Proliferation and Differentiation

NASA Astrophysics Data System (ADS)

Abrahamse, H.; de Villiers, J.; Mvula, B.

2009-06-01

There are two fundamental types of stem cells: Embryonic Stem cells and Adult Stem cells. Adult Stem cells have a more restricted potential and can usually differentiate into a few different cell types. In the body these cells facilitate the replacement or repair of damaged or diseased cells in organs. Low intensity laser irradiation was shown to increase stem cell migration and stimulate proliferation and it is thought that treatment of these cells with laser irradiation may increase the stem cell harvest and have a positive effect on the viability and proliferation. Our research is aimed at determining the effect of laser irradiation on differentiation of Adipose Derived Stem Cells (ADSCs) into different cell types using a diode laser with a wavelength of 636 nm and at 5 J/cm2. Confirmation of stem cell characteristics and well as subsequent differentiation were assessed using Western blot analysis and cellular morphology supported by fluorescent live cell imaging. Functionality of subsequent differentiated cells was confirmed by measuring adenosine triphosphate (ATP) production and cell viability.

Alpha-fetoprotein, stem cells and cancer: how study of the production of alpha-fetoprotein during chemical hepatocarcinogenesis led to reaffirmation of the stem cell theory of cancer.

PubMed

Sell, Stewart

2008-01-01

Identification of the cells in the liver that produce alpha-fetoprotein during development, in response to liver injury and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas. When the cellular changes in these processes were compared to that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue-determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as normal tissues: stem cells, transit-amplifying cells and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, antiangiogenesis and differentiation therapy) are directed against the cancer transit-amplifying cells. When these therapies are discontinued, the cancer reforms from the cancer stem cells. Therapy directed toward interruption of the cell signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of regrowth of the cancer. Copyright 2008 S. Karger AG, Basel.

ALPHA-FETOPROTEIN (AFP), STEM CELLS, AND CANCER: HOW STUDY OF THE PRODUCTION OF AFP DURING CHEMICAL HEPATOCARCINOGENESIS LED TO REAFFIRMATION OF THE STEM CELL THEORY OF CANCER

PubMed Central

Sell, Stewart

2008-01-01

Identification of the cells in the liver that produce alpha-fetoprotein (AFP) during development, in response to liver injury, and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas (HCC). When the cellular changes in these processes were compared that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as do normal tissues: stem cells, transit-amplifying cells, and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, anti-angiogenesis and differentiation therapy) are directed against the cancer transit amplifying cells. When these therapies are discontinued, the cancer re-forms from the cancer stem cells. Therapy directed toward interruption of the cell-signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of re-growth of the cancer. PMID:18612221

A Comparative Transcriptomic Analysis Reveals Conserved Features of Stem Cell Pluripotency in Planarians and Mammals

PubMed Central

Labbé, Roselyne M.; Irimia, Manuel; Currie, Ko W.; Lin, Alexander; Zhu, Shu Jun; Brown, David D.R.; Ross, Eric J.; Voisin, Veronique; Bader, Gary D.; Blencowe, Benjamin J.; Pearson, Bret J.

2014-01-01

Many long-lived species of animals require the function of adult stem cells throughout their lives. However, the transcriptomes of stem cells in invertebrates and vertebrates have not been compared, and consequently, ancestral regulatory circuits that control stem cell populations remain poorly defined. In this study, we have used data from high-throughput RNA sequencing to compare the transcriptomes of pluripotent adult stem cells from planarians with the transcriptomes of human and mouse pluripotent embryonic stem cells. From a stringently defined set of 4,432 orthologs shared between planarians, mice and humans, we identified 123 conserved genes that are ≥5-fold differentially expressed in stem cells from all three species. Guided by this gene set, we used RNAi screening in adult planarians to discover novel stem cell regulators, which we found to affect the stem cell-associated functions of tissue homeostasis, regeneration, and stem cell maintenance. Examples of genes that disrupted these processes included the orthologs of TBL3, PSD12, TTC27, and RACK1. From these analyses, we concluded that by comparing stem cell transcriptomes from diverse species, it is possible to uncover conserved factors that function in stem cell biology. These results provide insights into which genes comprised the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency. PMID:22696458

Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential

PubMed Central

Worthley, Daniel L.; Churchill, Michael; Compton, Jocelyn T.; Tailor, Yagnesh; Rao, Meenakshi; Si, Yiling; Levin, Daniel; Schwartz, Matthew G.; Uygur, Aysu; Hayakawa, Yoku; Gross, Stefanie; Renz, Bernhard W.; Setlik, Wanda; Martinez, Ashley N.; Chen, Xiaowei; Nizami, Saqib; Lee, Heon Goo; Kang, H. Paco; Caldwell, Jon-Michael; Asfaha, Samuel; Westphalen, C. Benedikt; Graham, Trevor; Jin, Guangchun; Nagar, Karan; Wang, Hongshan; Kheirbek, Mazen A.; Kolhe, Alka; Carpenter, Jared; Glaire, Mark; Nair, Abhinav; Renders, Simon; Manieri, Nicholas; Muthupalani, Sureshkumar; Fox, James G.; Reichert, Maximilian; Giraud, Andrew S.; Schwabe, Robert F.; Pradere, Jean-Phillipe; Walton, Katherine; Prakash, Ajay; Gumucio, Deborah; Rustgi, Anil K.; Stappenbeck, Thaddeus S.; Friedman, Richard A.; Gershon, Michael D.; Sims, Peter; Grikscheit, Tracy; Lee, Francis Y.; Karsenty, Gerard; Mukherjee, Siddhartha; Wang, Timothy C.

2014-01-01

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs). PMID:25594183

Biochemistry of epidermal stem cells.

PubMed

Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

2013-02-01

The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Basics and applications of stem cells in the pancreas.

PubMed

Sekine, Keisuke; Taniguchi, Hideki

2012-11-01

Enormous efforts have been made to establish pancreatic stem/progenitor cells as a source for regenerative medicine for the treatment of diabetes mellitus. In recent years, it has been recognized that the self-renewal of beta cells is the dominant process involved in postnatal beta-cell regeneration and expansion. Nevertheless, several in-vitro studies have suggested that ductal or as yet unidentified cells are candidates for pancreatic stem/progenitor cells that can differentiate into multilineage cells, including insulin(+) cells. The question remains as to whether beta cells are generated postnatally from stem/progenitor cells other than pre-existing beta cells. Furthermore, mutated pancreatic stem cells are considered to be prospective candidates for cancer stem cells or tumor-initiating cells. This review highlights recent progress in pancreatic stem/progenitor cell research.

Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

PubMed

Youssef, Mary; Krish, Varsha S; Kirshenbaum, Greer S; Atsak, Piray; Lass, Tamara J; Lieberman, Sophie R; Leonardo, E David; Dranovsky, Alex

2018-05-09

Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum et al., 2014), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

State performance in pluripotent and adult stem cell research, 2009-2016.

PubMed

Surani, Sana H; Levine, Aaron D

2018-04-01

To examine how the geographic distribution of pluripotent and adult stem cell research publications within the USA differs from other areas of biomedical research. Publication count data for pluripotent stem cell research, adult stem cell research and a comparison group representative of biomedical research more broadly were collected and analyzed for each US state from 2009 to 2016. The distribution of pluripotent stem cell research differed from the other fields with overperformance in pluripotent stem cell research observed in California, as well as Wisconsin, Massachusetts, Maryland and Connecticut. Our analysis suggests that permissive state stem cell policy may be one of the several factors contributing to strong state performance in pluripotent stem cell research.

Stem cell clinics online: the direct-to-consumer portrayal of stem cell medicine.

PubMed

Lau, Darren; Ogbogu, Ubaka; Taylor, Benjamin; Stafinski, Tania; Menon, Devidas; Caulfield, Timothy

2008-12-04

Despite the immature state of stem cell medicine, patients are seeking and accessing putative stem cell therapies in an "early market" in which direct-to-consumer advertising via the internet likely plays an important role. We analyzed stem cell clinic websites and appraised the relevant published clinical evidence of stem cell therapies to address three questions about the direct-to-consumer portrayal of stem cell medicine in this early market: What sorts of therapies are being offered? How are they portrayed? Is there clinical evidence to support the use of these therapies? We found that the portrayal of stem cell medicine on provider websites is optimistic and unsubstantiated by peer-reviewed literature.

Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior

NASA Astrophysics Data System (ADS)

Flores, Ignacio; Cayuela, María L.; Blasco, María A.

2005-08-01

A key process in organ homeostasis is the mobilization of stem cells out of their niches. We show through analysis of mouse models that telomere length, as well as the catalytic component of telomerase, Tert, are critical determinants in the mobilization of epidermal stem cells. Telomere shortening inhibited mobilization of stem cells out of their niche, impaired hair growth, and resulted in suppression of stem cell proliferative capacity in vitro. In contrast, Tert overexpression in the absence of changes in telomere length promoted stem cell mobilization, hair growth, and stem cell proliferation in vitro. The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging.

Prospects for neural stem cell-based therapies for neurological diseases.

PubMed

Imitola, Jaime

2007-10-01

Neural stem and progenitor cells have great potential for the treatment of neurological disorders. However, many obstacles remain to translate this field to the patient's bedside, including rationales for using neural stem cells in individual neurological disorders; the challenges of neural stem cell biology; and the caveats of current strategies of isolation and culturing neural precursors. Addressing these challenges is critical for the translation of neural stem cell biology to the clinic. Recent work using neural stem cells has yielded novel biologic concepts such as the importance of the reciprocal interaction between neural stem cells and the neurodegenerative environment. The prospect of using transplants of neural stem cells and progenitors to treat neurological diseases requires a better understanding of the molecular mechanisms of both neural stem cell behavior in experimental models and the intrinsic repair capacity of the injured brain.

Impact of genomic damage and ageing on stem cell function

PubMed Central

Behrens, Axel; van Deursen, Jan M.; Rudolph, K. Lenhard; Schumacher, Björn

2014-01-01

Impairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells. PMID:24576896

Lgr proteins in epithelial stem cell biology.

PubMed

Barker, Nick; Tan, Shawna; Clevers, Hans

2013-06-01

The ultimate success of global efforts to exploit adult stem cells for regenerative medicine will depend heavily on the availability of robust, highly selective stem cell surface markers that facilitate the isolation of stem cells from human tissues. Any subsequent expansion or manipulation of isolated stem cells will also require an intimate knowledge of the mechanisms that regulate these cells, to ensure maintenance of their regenerative capacities and to minimize the risk of introducing undesirable growth traits that could pose health risks for patients. A subclass of leucine-rich repeat-containing G-protein-coupled receptor (Lgr) proteins has recently gained prominence as adult stem cell markers with crucial roles in maintaining stem cell functions. Here, we discuss the major impact that their discovery has had on our understanding of adult stem cell biology in various self-renewing tissues and in accelerating progress towards the development of effective stem cell therapies.

Nanotechnology in the regulation of stem cell behavior

NASA Astrophysics Data System (ADS)

Wu, King-Chuen; Tseng, Ching-Li; Wu, Chi-Chang; Kao, Feng-Chen; Tu, Yuan-Kun; So, Edmund C.; Wang, Yang-Kao

2013-10-01

Stem cells are known for their potential to repair damaged tissues. The adhesion, growth and differentiation of stem cells are likely controlled by the surrounding microenvironment which contains both chemical and physical cues. Physical cues in the microenvironment, for example, nanotopography, were shown to play important roles in stem cell fate decisions. Thus, controlling stem cell behavior by nanoscale topography has become an important issue in stem cell biology. Nanotechnology has emerged as a new exciting field and research from this field has greatly advanced. Nanotechnology allows the manipulation of sophisticated surfaces/scaffolds which can mimic the cellular environment for regulating cellular behaviors. Thus, we summarize recent studies on nanotechnology with applications to stem cell biology, including the regulation of stem cell adhesion, growth, differentiation, tracking and imaging. Understanding the interactions of nanomaterials with stem cells may provide the knowledge to apply to cell-scaffold combinations in tissue engineering and regenerative medicine.

Characterization of Amniotic Stem Cells

PubMed Central

Koike, Chika; Zhou, Kaixuan; Takeda, Yuji; Fathy, Moustafa; Okabe, Motonori; Yoshida, Toshiko; Nakamura, Yukio; Kato, Yukio

2014-01-01

Abstract The amnion membrane is developed from embryo-derived cells, and amniotic cells have been shown to exhibit multidifferentiation potential. These cells represent a desirable source for stem cells for a variety of reasons. However, to date very few molecular analyses of amnion-derived cells have been reported, and efficient markers for isolating the stem cells remain unclear. This paper assesses the characterization of amnion-derived cells as stem cells by examining stemness marker expressions for amnion-derived epithelial cells and mesenchymal cells by flow cytometry, immunocytochemistry, and quantitative PCR. Flow cytometry revealed that amnion epithelial cells expressed CD133, CD 271, and TRA-1-60, whereas mecenchymal cells expressed CD44, CD73, CD90, and CD105. Immunohistochemistry showed that both cells expressed the stemness markers Oct3/4, Sox2, Klf4, and SSEA4. Stemness genes' expression in amnion epithelial cells, mesenchymal cells, fibroblast, bone marrow–derived mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) was compared by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Amnion-derived epithelial cells and mesenchymal cells expressed Oct3/4, Nanog, and Klf4 more than bone marrow–derived MSCs. The sorted TRA1-60–positive cells expressed Oct3/4, Nanog, and Klf4 more than unsorted cells or TRA1-60–negative cells. TRA1-60 can be a marker for isolating amnion epithelial stem cells. PMID:25068631

Electroporation of the Testis

NASA Astrophysics Data System (ADS)

Yomogida, Kentaro

The mature mammalian testis is a marvelous organ that produces numerous sperm cells during its reproductive phase. This biologically significant process consists of three steps: stem cell self-renewal and differentiation, meiosis and genetic recombination, and haploid cell morphogenesis into sperm (Russell et al., 1990). The first step provides a good model for investigating the molecular mechanism of stem cell regulation. Currently, the mechanism underlying sperm cell production is a very exciting topic in regenerative medicine (Lensch et al. 2007; Okita et al., 2007). The spermatogonial stem cell system has several advantages, including the easy histological identification of stem cells (Russell et al., 1990), a clear relationship between stem cells and the supporting Sertoli cells, which provide a stem cell niche (Tadokoro et al., 2002; Yomogida et al., 2003), and a transplantation assay for stem cell activity (Oatley & Brinster, 2006). Although germline stem (GS) cells derived from the gonocytes in newborn testis constitute a suitable in vitro system for investigating the properties of spermatogonial stem cells (Kanatsu-Shinohara et al., 2003, 2004), studies using living mammalian testes continue to provide information regarding the roles of the stem cell niche. In vivo electroporation of the supporting cells in the testis will expand our ability to study it.

Current applications of human pluripotent stem cells: possibilities and challenges.

PubMed

Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

2012-01-01

Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.

PubMed

Miyahara, Yoshinori; Nagaya, Noritoshi; Kataoka, Masaharu; Yanagawa, Bobby; Tanaka, Koichi; Hao, Hiroyuki; Ishino, Kozo; Ishida, Hideyuki; Shimizu, Tatsuya; Kangawa, Kenji; Sano, Shunji; Okano, Teruo; Kitamura, Soichiro; Mori, Hidezo

2006-04-01

Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.

Genetic and epigenetic instability of stem cells.

PubMed

Rajamani, Karthyayani; Li, Yuan-Sheng; Hsieh, Dean-Kuo; Lin, Shinn-Zong; Harn, Horng-Jyh; Chiou, Tzyy-Wen

2014-01-01

Recently, research on stem cells has been receiving an increasing amount of attention, both for its advantages and disadvantages. Genetic and epigenetic instabilities among stem cells have been a recurring obstacle to progress in regenerative medicine using stem cells. Various reports have stated that these instabilities can transform stem cells when transferred in vivo and thus have the potential to develop tumors. Previous research has shown that various extrinsic and intrinsic factors can contribute to the stability of stem cells. The extrinsic factors include growth supplements, growth factors, oxygen tension, passage technique, and cryopreservation. Controlling these factors based on previous reports may assist researchers in developing strategies for the production and clinical application of "safe" stem cells. On the other hand, the intrinsic factors can be unpredictable and uncontrollable; therefore, to ensure the successful use of stem cells in regenerative medicine, it is imperative to develop and implement appropriate strategies and technique for culturing stem cells and to confirm the genetic and epigenetic safety of these stem cells before employing them in clinical trials.

Dipeptide species regulate p38MAPK–Smad3 signalling to maintain chronic myelogenous leukaemia stem cells

PubMed Central

Naka, Kazuhito; Jomen, Yoshie; Ishihara, Kaori; Kim, Junil; Ishimoto, Takahiro; Bae, Eun-Jin; Mohney, Robert P.; Stirdivant, Steven M.; Oshima, Hiroko; Oshima, Masanobu; Kim, Dong-Wook; Nakauchi, Hiromitsu; Takihara, Yoshihiro; Kato, Yukio; Ooshima, Akira; Kim, Seong-Jin

2015-01-01

Understanding the specific survival of the rare chronic myelogenous leukaemia (CML) stem cell population could provide a target for therapeutics aimed at eradicating these cells. However, little is known about how survival signalling is regulated in CML stem cells. In this study, we survey global metabolic differences between murine normal haematopoietic stem cells (HSCs) and CML stem cells using metabolomics techniques. Strikingly, we show that CML stem cells accumulate significantly higher levels of certain dipeptide species than normal HSCs. Once internalized, these dipeptide species activate amino-acid signalling via a pathway involving p38MAPK and the stemness transcription factor Smad3, which promotes CML stem cell maintenance. Importantly, pharmacological inhibition of dipeptide uptake inhibits CML stem cell activity in vivo. Our results demonstrate that dipeptide species support CML stem cell maintenance by activating p38MAPK–Smad3 signalling in vivo, and thus point towards a potential therapeutic target for CML treatment. PMID:26289811

Engineering Stem Cells for Biomedical Applications.

PubMed

Yin, Perry T; Han, Edward; Lee, Ki-Bum

2016-01-07

Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications. These engineered stem cells can take on a number of forms. For instance, engineered stem cells encompass the genetic modification of stem cells as well as the use of stem cells for gene delivery, nanoparticle loading and delivery, and even small molecule drug delivery. The present Review gives an in-depth account of the current status of engineered stem cells, including potential cell sources, the most common methods used to engineer stem cells, and the utilization of engineered stem cells in various biomedical applications, with a particular focus on tissue regeneration, the treatment of immunodeficiency diseases, and cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling TSC and LAM Using Patient Derived Induced Pluripotent Stem Cells

DTIC Science & Technology

2016-10-01

lentiviral knockdown, and CRISPR /Cas9 genome editing in embryonic stem cells (ESCs). We have characterized the iPSCs extensively and found that they display...induced pluripotent stem cells (iPSCs) embryonic stem cells (ESCs) reprogramming CRISPR /Cas9 genome editing neural stem cells (NSCs) neural crest... CRISPR /cas9 in two additional human pluripotent stem cell lines (WA07 (H7) – female cell line registry #0061; and a control male iPSC lines generated

Biochemistry of epidermal stem cells☆

PubMed Central

Eckert, Richard L.; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan C.; Boucher, Shayne E.; Bickenbach, Jackie R.; Kerr, Candace

2014-01-01

Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. PMID:22820019

Cryopreservation of Human Stem Cells for Clinical Application: A Review

PubMed Central

Hunt, Charles J.

2011-01-01

Summary Stem cells have been used in a clinical setting for many years. Haematopoietic stem cells have been used for the treatment of both haematological and non-haematological disease; while more recently mesenchymal stem cells derived from bone marrow have been the subject of both laboratory and early clinical studies. Whilst these cells show both multipotency and expansion potential, they nonetheless do not form stable cell lines in culture which is likely to limit the breadth of their application in the field of regenerative medicine. Human embryonic stem cells are pluripotent cells, capable of forming stable cell lines which retain the capacity to differentiate into cells from all three germ layers. This makes them of special significance in both regenerative medicine and toxicology. Induced pluripotent stem (iPS) cells may also provide a similar breadth of utility without some of the confounding ethical issues surrounding embryonic stem cells. An essential pre-requisite to the commercial and clinical application of stem cells are suitable cryopreservation protocols for long-term storage. Whilst effective methods for cryopreservation and storage have been developed for haematopoietic and mesenchymal stem cells, embryonic cells and iPS cells have proved more refractory. This paper reviews the current state of cryopreservation as it pertains to stem cells and in particular the embryonic and iPS cell. PMID:21566712

Cryopreservation of Human Stem Cells for Clinical Application: A Review.

PubMed

Hunt, Charles J

2011-01-01

SUMMARY: Stem cells have been used in a clinical setting for many years. Haematopoietic stem cells have been used for the treatment of both haematological and non-haematological disease; while more recently mesenchymal stem cells derived from bone marrow have been the subject of both laboratory and early clinical studies. Whilst these cells show both multipotency and expansion potential, they nonetheless do not form stable cell lines in culture which is likely to limit the breadth of their application in the field of regenerative medicine. Human embryonic stem cells are pluripotent cells, capable of forming stable cell lines which retain the capacity to differentiate into cells from all three germ layers. This makes them of special significance in both regenerative medicine and toxicology. Induced pluripotent stem (iPS) cells may also provide a similar breadth of utility without some of the confounding ethical issues surrounding embryonic stem cells. An essential pre-requisite to the commercial and clinical application of stem cells are suitable cryopreservation protocols for long-term storage. Whilst effective methods for cryopreservation and storage have been developed for haematopoietic and mesenchymal stem cells, embryonic cells and iPS cells have proved more refractory. This paper reviews the current state of cryopreservation as it pertains to stem cells and in particular the embryonic and iPS cell.

YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Dasol; Byun, Sung-Hyun; Park, Soojeong

Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and sizemore » of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.« less

Recent progress in stem cell differentiation directed by material and mechanical cues.

PubMed

Lin, Xunxun; Shi, Yuan; Cao, Yilin; Liu, Wei

2016-02-02

Stem cells play essential roles in tissue regeneration in vivo via specific lineage differentiation induced by environmental factors. In the past, biochemical signals were the focus of induced stem cell differentiation. As reported by Engler et al (2006 Cell 126 677-89), biophysical signal mediated stem cell differentiation could also serve as an important inducer. With the advancement of material science, it becomes a possible strategy to generate active biophysical signals for directing stem cell fate through specially designed material microstructures. In the past five years, significant progress has been made in this field, and these designed biophysical signals include material elasticity/rigidity, micropatterned structure, extracellular matrix (ECM) coated materials, material transmitted extracellular mechanical force etc. A large number of investigations involved material directed differentiation of mesenchymal stem cells, neural stem/progenitor cells, adipose derived stem cells, hematopoietic stem/progenitor cells, embryonic stem cells and other cells. Hydrogel based materials were commonly used to create varied mechanical properties via modifying the ratio of different components, crosslinking levels, matrix concentration and conjugation with other components. Among them, polyacrylamide (PAM) and polydimethylsiloxane (PDMS) hydrogels remained the major types of material. Specially designed micropatterning was not only able to create a unique topographical surface to control cell shape, alignment, cell-cell and cell-matrix contact for basic stem cell biology study, but also could be integrated with 3D bioprinting to generate micropattered 3D structure and thus to induce stem cell based tissue regeneration. ECM coating on a specific topographical structure was capable of inducing even more specific and potent stem cell differentiation along with soluble factors and mechanical force. The article overviews the progress of the past five years in this particular field.

Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche.

PubMed

Madl, Christopher M; Heilshorn, Sarah C

2018-06-04

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell-cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.

Incorporation of Biomaterials in Multicellular Aggregates Modulates Pluripotent Stem Cell Differentiation

PubMed Central

Bratt-Leal, Andrés M.; Carpenedo, Richard L.; Ungrin, Mark; Zandstra, Peter W.; McDevitt, Todd C.

2010-01-01

Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell-biomaterial interactions have largely been studied by introducing stem cells into artificial environments, such as 2D cell culture on biomaterial surfaces, encapsulation of cell suspensions within hydrogel materials, or cell seeding on 3D polymeric scaffolds. In this study, microparticles fabricated from different materials, such as agarose, PLGA and gelatin, were stably integrated, in a dose-dependent manner, within aggregates of pluripotent stem cells (PSCs) prior to differentiation as a means to directly examine stem cell-biomaterial interactions in 3D. Interestingly, the presence of the materials within the stem cell aggregates differentially modulated the gene and protein expression patterns of several differentiation markers without adversely affecting cell viability. Microparticle incorporation within 3D stem cell aggregates can control the spatial presentation of extracellular environmental cues (i.e. soluble factors, extracellular matrix and intercellular adhesion molecules) as a means to direct the differentiation of stem cells for tissue engineering and regenerative medicine applications. In addition, these results suggest that the physical presence of microparticles within stem cell aggregates does not compromise PSC differentiation, but in fact the choice of biomaterials can impact the propensity of stem cells to adopt particular differentiated cell phenotypes. PMID:20864164

Markers for the identification of tendon-derived stem cells in vitro and tendon stem cells in situ - update and future development.

PubMed

Lui, Pauline Po Yee

2015-06-02

The efficacy of tendon-derived stem cells (TDSCs) for the promotion of tendon and tendon-bone junction repair has been reported in animal studies. Modulation of the tendon stem cell niche in vivo has also been reported to influence tendon structure. There is a need to have specific and reliable markers that can define TDSCs in vitro and tendon stem cells in situ for several reasons: to understand the basic biology of TDSCs and their subpopulations in vitro; to understand the identity, niches and functions of tendon/progenitor stem cells in vivo; to meet the governmental regulatory requirements for quality of TDSCs when translating the exciting preclinical findings into clinical trial/practice; and to develop new treatment strategies for mobilizing endogenous stem/progenitor cells in tendon. TDSCs were reported to express the common mesenchymal stem cell (MSC) markers and some embryonic stem cell (ESC) markers, and there were attempts to use these markers to label tendon stem cells in situ. Are these stem cell markers useful for the identification of TDSCs in vitro and tracking of tendon stem cells in situ? This review aims to discuss the values of the panel of MSC, ESC and tendon-related markers for the identification of TDSCs in vitro. Important factors influencing marker expression by TDSCs are discussed. The usefulness and limitations of the panel of MSC, ESC and tendon-related markers for tracking stem cells in tendon, especially tendon stem cells, in situ are then reviewed. Future research directions are proposed.

Haematopoietic stem and progenitor cells from human pluripotent stem cells

PubMed Central

Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

2018-01-01

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure.

PubMed

Yun, Hongmin; Zhou, Yi; Wills, Andrew; Du, Yiqin

2016-06-01

Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration.

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

PubMed Central

Yun, Hongmin; Zhou, Yi; Wills, Andrew

2016-01-01

Abstract Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration. PMID:27183473

New perspectives in human stem cell therapeutic research.

PubMed

Trounson, Alan

2009-06-11

Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action of many of these cells are unknown and this raises the concern of unpredictable results in the future. Nevertheless there is considerable optimism that immune suppression and anti-inflammatory properties of mesenchymal stem cells will be of benefit for many conditions such as graft versus host disease, solid organ transplants and pulmonary fibrosis. Where bone marrow and mesenchymal stem cells are being studied for heart disease, stroke and other neurodegenerative disorders, again progress is mixed and mostly without significant benefit. However, correction of multiple sclerosis, at least in the short term is encouraging. Clinical trials on the use of embryonic stem cell derivatives for spinal injury and macular degeneration are beginning and a raft of other clinical trials can be expected soon, for example, the use of neural stem cells for killing inoperable glioma and embryonic stem cells for regenerating beta islet cells for diabetes. The change in attitude to embryonic stem cell research with the incoming Obama administration heralds a new co-operative environment for study and evaluation of stem cell therapies. The Californian stem cell initiative (California Institute for Regenerative Medicine) has engendered global collaboration for this new medicine that will now also be supported by the US Federal Government. The active participation of governments, academia, biotechnology, pharmaceutical companies, and private investment is a powerful consortium for advances in health.

Invincible, but not invisible: imaging approaches toward in vivo detection of cancer stem cells.

PubMed

Hart, Lori S; El-Deiry, Wafik S

2008-06-10

With evidence emerging in support of a cancer stem-cell model of carcinogenesis, it is of paramount importance to identify and image these elusive cells in their natural environment. The cancer stem-cell hypothesis has the potential to explain unresolved questions of tumorigenesis, tumor heterogeneity, chemotherapeutic and radiation resistance, and even the metastatic phenotype. Intravital imaging of cancer stem cells could be of great value for determining prognosis, as well as monitoring therapeutic efficacy and influencing therapeutic protocols. Cancer stem cells represent a rare population of cells, as low as 0.1% of cells within a human tumor, and the phenotype of isolated cancer stem cells is easily altered when placed under in vitro conditions. This represents a challenge in studying cancer stem cells without manipulation or extraction from their natural environment. Advanced imaging techniques allow for the in vivo observation of physiological events at cellular resolution. Cancer stem-cell studies must take advantage of such technology to promote a better understanding of the cancer stem-cell model in relation to tumor growth and metastasis, as well as to potentially improve on the principles by which cancers are treated. This review examines the opportunities for in vivo imaging of putative cancer stem cells with regard to currently accepted cancer stem-cell characteristics and advanced imaging technologies.

Neural stem cell-based treatment for neurodegenerative diseases.

PubMed

Kim, Seung U; Lee, Hong J; Kim, Yun B

2013-10-01

Human neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generation of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenerative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury. © 2013 Japanese Society of Neuropathology.

Constitutive Proteasomal Degradation of TWIST-1 in Epithelial Ovarian Cancer Stem Cells Impacts Differentiation and Metastatic Potential

PubMed Central

Yin, Gang; Alvero, Ayesha B.; Craveiro, Vinicius; Holmberg, Jennie C.; Fu, Han-Hsuan; Montagna, Michele K.; Yang, Yang; Chefetz-Menaker, Ilana; Nuti, Sudhakar; Rossi, Michael; Silasi, Dan-Arin; Rutherford, Thomas; Mor, Gil

2013-01-01

Epithelial-mesenchymal transition (EMT) is a critical process for embryogenesis but is abnormally activated during cancer metastasis and recurrence. This process enables epithelial cancer cells to acquire mobility and traits associated with stemness. It is unknown whether epithelial stem cells or epithelial cancer stem cells are able to undergo EMT, and what molecular mechanism regulates this process in these specific cell types. We found that Epithelial Ovarian Cancer Stem cells (EOC stem cells) are the source of metastatic progenitor cells through a differentiation process involving EMT and Mesenchymal-Epithelial Transition (MET). We demonstrate both in vivo and in vitro the differentiation of EOC stem cells into mesenchymal spheroid-forming cells (MSFCs) and their capacity to initiate an active carcinomatosis. Furthermore, we demonstrate that human EOC stem cells injected i.p in mice are able to form ovarian tumors, suggesting that the EOC stem cells have the ability to “home” to the ovaries and establish tumors. Most interestingly, we found that TWIST1 is constitutively degraded in EOC stem cells, and that the acquisition of TWIST1 requires additional signals that will trigger the differentiation process. These findings are relevant for understanding the differentiation and metastasis process in EOC stem cells. PMID:22349827

Hepatic differentiation of pluripotent stem cells.

PubMed

Loya, Komal; Eggenschwiler, Reto; Ko, Kinarm; Sgodda, Malte; André, Francoise; Bleidissel, Martina; Schöler, Hans R; Cantz, Tobias

2009-10-01

In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine.

Effect of Dedifferentiation on Time to Mutation Acquisition in Stem Cell-Driven Cancers

PubMed Central

Jilkine, Alexandra; Gutenkunst, Ryan N.

2014-01-01

Accumulating evidence suggests that many tumors have a hierarchical organization, with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells. It is unclear, however, whether cancer stem cells originate from normal stem cells or from dedifferentiated progenitor cells. To address this, we mathematically modeled the effect of dedifferentiation on carcinogenesis. We considered a hybrid stochastic-deterministic model of mutation accumulation in both stem cells and progenitors, including dedifferentiation of progenitor cells to a stem cell-like state. We performed exact computer simulations of the emergence of tumor subpopulations with two mutations, and we derived semi-analytical estimates for the waiting time distribution to fixation. Our results suggest that dedifferentiation may play an important role in carcinogenesis, depending on how stem cell homeostasis is maintained. If the stem cell population size is held strictly constant (due to all divisions being asymmetric), we found that dedifferentiation acts like a positive selective force in the stem cell population and thus speeds carcinogenesis. If the stem cell population size is allowed to vary stochastically with density-dependent reproduction rates (allowing both symmetric and asymmetric divisions), we found that dedifferentiation beyond a critical threshold leads to exponential growth of the stem cell population. Thus, dedifferentiation may play a crucial role, the common modeling assumption of constant stem cell population size may not be adequate, and further progress in understanding carcinogenesis demands a more detailed mechanistic understanding of stem cell homeostasis. PMID:24603301

Generation and characterisation of decellularised human corneal limbus.

PubMed

Spaniol, Kristina; Witt, Joana; Mertsch, Sonja; Borrelli, Maria; Geerling, Gerd; Schrader, Stefan

2018-03-01

Limbal epithelial stem cells (LESC) reside in a niche in the corneo-scleral transition zone. Deficiency leads to pain, corneal opacity, and eventually blindness. LESC transplantation of ex-vivo expanded human LESC on a carrier such as human amniotic membrane is a current treatment option. We evaluated decellularised human limbus (DHL) as a potential carrier matrix for the transplantation of LESC. Human corneas were obtained from the local eye bank. The limbal tissue was decellularised by sodium desoxychelate and DNase solution and sterilised by γ-irradiation. Native limbus- and DHL-surface structures were assessed by scanning electron microscopy and collagen ultrastructure using transmission electron microscopy. Presence and preservation of limbal basement membrane proteins in native limbus and DHL were analysed immunohistochemically. Absence of DNA after decellularisation was assessed by Feulgen staining and DNA quantification. Presence of immune cells was explored by CD45 staining, and potential cytotoxicity was tested using a cell viability assay. In the DHL, the DNA content was reduced from 1.5 ± 0.3 μg/mg to 0.15 ± 0.01 μg/mg; the three-dimensional structure and the arrangement of the collagen fibrils were preserved. Main basement membrane proteins such as collagen IV, laminin, and fibronectin were still present after decellularisation and γ-irradiation. CD45-expressing cells were evident neither in the native limbus nor in the DHL. DHL did not convey cytotoxicity. The extracellular matrix (ECM) of the limbus provides a tissue specific morphology and three-dimensionality consisting of particular ECM proteins. It therefore represents a substantial component of the stem cell niche. The DHL provides a specific limbal niche surrounding, and might serve as an easily producible carrier matrix for LESC transplantation.

Effect of different freezing rates during cryopreservation of rat mesenchymal stem cells using combinations of hydroxyethyl starch and dimethylsulfoxide

PubMed Central

2012-01-01

Background Mesenchymal stem cells (MSCs) are increasingly used as therapeutic agents as well as research tools in regenerative medicine. Development of technologies which allow storing and banking of MSC with minimal loss of cell viability, differentiation capacity, and function is required for clinical and research applications. Cryopreservation is the most effective way to preserve cells long term, but it involves potentially cytotoxic compounds and processing steps. Here, we investigate the effect of decreasing dimethyl sulfoxide (DMSO) concentrations in cryosolution by substituting with hydroxyethyl starch (HES) of different molecular weights using different freezing rates. Post-thaw viability, phenotype and osteogenic differentiation capacity of MSCs were analysed. Results The study confirms that, for rat MSC, cryopreservation effects need to be assessed some time after, rather than immediately after thawing. MSCs cryopreserved with HES maintain their characteristic cell surface marker expression as well as the osteogenic, adipogenic and chondrogenic differentiation potential. HES alone does not provide sufficient cryoprotection for rat MSCs, but provides good cryoprotection in combination with DMSO, permitting the DMSO content to be reduced to 5%. There are indications that such a combination would seem useful not just for the clinical disadvantages of DMSO but also based on a tendency for reduced osteogenic differentiation capacity of rat MSC cryopreserved with high DMSO concentration. HES molecular weight appears to play only a minor role in its capacity to act as a cryopreservation solution for MSC. The use of a ‘straight freeze’ protocol is no less effective in maintaining post-thaw viability of MSC compared to controlled rate freezing methods. Conclusion A 5% DMSO / 5% HES solution cryopreservation solution using a ‘straight freeze’ approach can be recommended for rat MSC. PMID:22889198

PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.

PubMed

Lin, Meng-Chieh; Chen, Shih-Yin; Tsai, Ho-Min; He, Pei-Lin; Lin, Yen-Chun; Herschman, Harvey; Li, Hua-Jung

2017-02-01

Prostaglandin E 2 (PGE 2 )-initiated signaling contributes to stem cell homeostasis and regeneration. However, it is unclear how PGE 2 signaling controls cell stemness. This study identifies a previously unknown mechanism by which PGE 2 /prostaglandin E receptor 4 (EP 4 ) signaling regulates multiple signaling pathways (e.g., PI3K/Akt signaling, TGFβ signaling, Wnt signaling, EGFR signaling) which maintain the basal mammary stem cell phenotype. A shift of basal mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non-basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP 4 ) antagonism. EP 4 antagonists elicit release of signaling components, by controlling their trafficking into extracellular vesicles/exosomes in a lipid raft/caveolae-dependent manner. Consequently, EP 4 antagonism indirectly inactivates, through induced extracellular vesicle/exosome release, pathways required for mammary epithelial stem cell homeostasis, e.g. canonical/noncanonical Wnt, TGFβ and PI3K/Akt pathways. EP 4 antagonism causes signaling receptors and signaling components to shift from non-lipid raft fractions to lipid raft fractions, and to then be released in EP 4 antagonist-induced extracellular vesicles/exosomes, resulting in the loss of the stem cell state by mammary epithelial stem cells. In contrast, luminal mammary epithelial cells can acquire basal stem cell properties following ingestion of EP 4 antagonist-induced stem cell extracellular vesicles/exosomes, and can then form mammary glands. These findings demonstrate that PGE 2 /EP 4 signaling controls homeostasis of mammary epithelial stem cells through regulating extracellular vesicle/exosome release. Reprogramming of mammary epithelial cells can result from EP 4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells. Stem Cells 2017;35:425-444. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals.

PubMed

Decotto, Eva; Spradling, Allan C

2005-10-01

The stem cell niches at the apex of Drosophila ovaries and testes have been viewed as distinct in two major respects. While both contain germline stem cells, the testis niche also contains "cyst progenitor" stem cells, which divide to produce somatic cells that encase developing germ cells. Moreover, while both niches utilize BMP signaling, the testis niche requires a key JAK/STAT signal. We now show, by lineage marking, that the ovarian niche also contains a second type of stem cell. These "escort stem cells" morphologically resemble testis cyst progenitor cells and their daughters encase developing cysts before undergoing apoptosis at the time of follicle formation. In addition, we show that JAK/STAT signaling also plays a critical role in ovarian niche function, and acts within escort cells. These observations reveal striking similarities in the stem cell niches of male and female gonads, and suggest that they are largely governed by common mechanisms.

Placenta-an alternative source of stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matikainen, Tiina; Laine, Jarmo

2005-09-01

The two most promising practical applications of human stem cells are cellular replacement therapies in human disease and toxicological screening of candidate drug molecules. Both require a source of human stem cells that can be isolated, purified, expanded in number and differentiated into the cell type of choice in a controlled manner. Currently, uses of both embryonic and adult stem cells are investigated. While embryonic stem cells are pluripotent and can differentiate into any specialised cell type, their use requires establishment of embryonic stem cell lines using the inner cell mass of an early pre-implantation embryo. As the blastocyst ismore » destroyed during the process, ethical issues need to be carefully considered. The use of embryonic stem cells is also limited by the difficulties in growing large numbers of the cells without inducing spontaneous differentiation, and the problems in controlling directed differentiation of the cells. The use of adult stem cells, typically derived from bone marrow, but also from other tissues, is ethically non-controversial but their differentiation potential is more limited than that of the embryonic stem cells. Since human cord blood, umbilical cord, placenta and amnion are normally discarded at birth, they provide an easily accessible alternative source of stem cells. We review the potential and current status of the use of adult stem cells derived from the placenta or umbilical cord in therapeutic and toxicological applications.« less

Pluripotent stem cells and reprogrammed cells in farm animals.

PubMed

Nowak-Imialek, Monika; Kues, Wilfried; Carnwath, Joseph W; Niemann, Heiner

2011-08-01

Pluripotent cells are unique because of their ability to differentiate into the cell lineages forming the entire organism. True pluripotent stem cells with germ line contribution have been reported for mice and rats. Human pluripotent cells share numerous features of pluripotentiality, but confirmation of their in vivo capacity for germ line contribution is impossible due to ethical and legal restrictions. Progress toward derivation of embryonic stem cells from domestic species has been made, but the derived cells were not able to produce germ line chimeras and thus are termed embryonic stem-like cells. However, domestic animals, in particular the domestic pig (Sus scrofa), are excellent large animals models, in which the clinical potential of stem cell therapies can be studied. Reprogramming technologies for somatic cells, including somatic cell nuclear transfer, cell fusion, in vitro culture in the presence of cell extracts, in vitro conversion of adult unipotent spermatogonial stem cells into germ line derived pluripotent stem cells, and transduction with reprogramming factors have been developed with the goal of obtaining pluripotent, germ line competent stem cells from domestic animals. This review summarizes the present state of the art in the derivation and maintenance of pluripotent stem cells in domestic animals.

Information on Stem Cell Research

MedlinePlus

... of stem cells share similar properties there are differences as well. For example, ES cells and iPS cells are able to differentiate into any type of cell, whereas adult stem cells are more restricted in their potential. The promise of all stem cells for use ...

The Development of Stem Cell-Based Treatment for Liver Failure.

PubMed

Zhu, Tiantian; Li, Yuwen; Guo, Yusheng; Zhu, Chuanlong

2017-01-01

Liver failure is a devastating clinical syndrome with a persistently mortality rate despite advanced care. Orthotopic liver transplantation protected patients from hepatic failure. Yet, limitations including postoperative complications, high costs, and shortages of donor organs defect its application. The development of stem cell therapy complements the deficiencies of liver transplantation, due to the inherent ability of stem cells to proliferate and differentiate. Understand the source of stem cells, as well as the advantages and disadvantages of stem cell therapy. Based on published papers, we discussed the cell sources and therapeutic effect of stem cells. We also summarized the pros and cons, as well as optimization of stem cell-based treatment. Finally outlook future prospects of stem cell therapy. Stem cells may be harvested from a variety of human tissues, and then used to promote the convalescence of hepatocellular function. The emergence of the co-cultured system, tissueengineered technology and genetic modfication has further enhanced the functionality of stem cells. However, the tumorigenicity, the low survival rate and the scarcity of long-term treatment effect are obstacles for the further development of stem cell therapy. In this review, we highlight current research findings and present the future prospects in the area of stem cell-based treatment for liver failure. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

76 FR 11491 - Advisory Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members AGENCY: Health... on Blood Stem Cell Transplantation. The Advisory Council on Blood Stem Cell Transplantation was...: Nominations should be submitted to the Executive Secretary, Advisory Council on Blood Stem Cell...

3 CFR - Guidelines for Human Stem Cell Research

Code of Federal Regulations, 2010 CFR

2010-01-01

... 3 The President 1 2010-01-01 2010-01-01 false Guidelines for Human Stem Cell Research Presidential Documents Other Presidential Documents Memorandum of July 30, 2009 Guidelines for Human Stem Cell Research..., scientifically worthy human stem cell research, including human embryonic stem cell research, to the extent...

Aging, metabolism and stem cells: Spotlight on muscle stem cells.

PubMed

García-Prat, Laura; Muñoz-Cánoves, Pura

2017-04-15

All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vitro spatially organizing the differentiation in individual multicellular stem cell aggregates.

PubMed

Qi, Hao; Huang, Guoyou; Han, Yu Long; Lin, Wang; Li, Xiujun; Wang, Shuqi; Lu, Tian Jian; Xu, Feng

2016-01-01

With significant potential as a robust source to produce specific somatic cells for regenerative medicine, stem cells have attracted increasing attention from both academia and government. In vivo, stem cell differentiation is a process under complicated regulations to precisely build tissue with unique spatial structures. Since multicellular spheroidal aggregates of stem cells, commonly called as embryoid bodies (EBs), are considered to be capable of recapitulating the events in early stage of embryonic development, a variety of methods have been developed to form EBs in vitro for studying differentiation of embryonic stem cells. The regulation of stem cell differentiation is crucial in directing stem cells to build tissue with the correct spatial architecture for specific functions. However, stem cells within the three-dimensional multicellular aggregates undergo differentiation in a less unpredictable and spatially controlled manner in vitro than in vivo. Recently, various microengineering technologies have been developed to manipulate stem cells in vitro in a spatially controlled manner. Herein, we take the spotlight on these technologies and researches that bring us the new potential for manipulation of stem cells for specific purposes.

Stem cells in nephrology: present status and future.

PubMed

Watorek, Ewa; Klinger, Marian

2006-01-01

Stem cell biology is currently developing rapidly because of the potential therapeutic utility of stem cells. The ability to acquire any desired phenotype raises hope for regenerative therapies. Manipulation of these cells is a potentially valuable tool; however, the mechanisms of stem cell differentiation and plasticity are currently beyond our control. In the field of nephrology, the presence of adult kidney stem cells has been debated. Renal adult stem cells may be descendants of some early kidney progenitors, or may be derived from bone marrow. Evidence of a hematopoietic stem-cell contribution to renal repair encourages the possibility of bone marrow or stem cell transplantation as a means of treating autoimmune glomerulopathies. The transplantation of fetal kidney tissue containing renal progenitors, which then develop into functional nephrons, is a step towards renal regeneration. According to recent reports, the development of functional nephrons from human mesenchymal stem cells in rodent whole-embryo culture is possible. Establishing in vitro self organs from autologous stem cells would be a promising therapeutic solution in light of the shortage of allogenic organs and the unresolved problem of chronic allograft rejection.

Socializing with the neighbors: stem cells and their niche.

PubMed

Fuchs, Elaine; Tumbar, Tudorita; Guasch, Geraldine

2004-03-19

The potential of stem cells in regenerative medicine relies upon removing them from their natural habitat, propagating them in culture, and placing them into a foreign tissue environment. To do so, it is essential to understand how stem cells interact with their microenvironment, the so-called stem cell niche, to establish and maintain their properties. In this review, we examine adult stem cell niches and their impact on stem cell biology.

Stem Cells News Update: A Personal Perspective

PubMed Central

Wong, SC

2013-01-01

This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy. PMID:24778557

Stem cells news update: a personal perspective.

PubMed

Wong, Sc

2013-12-01

This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy.

Platelet-rich plasma derived growth factors contribute to stem cell differentiation in musculoskeletal regeneration

NASA Astrophysics Data System (ADS)

Qian, Yun; Han, Qixin; Chen, Wei; Song, Jialin; Zhao, Xiaotian; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

2017-10-01

Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of platelet-rich plasma derived growth factors with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.

Elements of the niche for adult stem cell expansion

PubMed Central

Redondo, Patricia A; Pavlou, Marina; Loizidou, Marilena; Cheema, Umber

2017-01-01

Adult stem cells are crucial for tissue homeostasis. These cells reside within exclusive locations in tissues, termed niches, which protect adult stem cell fidelity and regulate their many functions through biophysical-, biochemical- and cellular-mediated mechanisms. There is a growing understanding of how these mechanisms and their components contribute towards maintaining stem cell quiescence, self-renewal, expansion and differentiation patterns. In vitro expansion of adult stem cells is a powerful tool for understanding stem cell biology, and for tissue engineering and regenerative medicine applications. However, it is technically challenging, since adult stem cell removal from their native microenvironment has negative repercussions on their sustainability. In this review, we overview specific elements of the biomimetic niche and how recreating such elements can help in vitro propagation of adult stem cells. PMID:28890779

Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration.

PubMed

Qian, Yun; Han, Qixin; Chen, Wei; Song, Jialin; Zhao, Xiaotian; Ouyang, Yuanming; Yuan, Weien; Fan, Cunyi

2017-01-01

Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of PRP derived GFs with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.

Elements of the niche for adult stem cell expansion.

PubMed

Redondo, Patricia A; Pavlou, Marina; Loizidou, Marilena; Cheema, Umber

2017-01-01

Adult stem cells are crucial for tissue homeostasis. These cells reside within exclusive locations in tissues, termed niches, which protect adult stem cell fidelity and regulate their many functions through biophysical-, biochemical- and cellular-mediated mechanisms. There is a growing understanding of how these mechanisms and their components contribute towards maintaining stem cell quiescence, self-renewal, expansion and differentiation patterns. In vitro expansion of adult stem cells is a powerful tool for understanding stem cell biology, and for tissue engineering and regenerative medicine applications. However, it is technically challenging, since adult stem cell removal from their native microenvironment has negative repercussions on their sustainability. In this review, we overview specific elements of the biomimetic niche and how recreating such elements can help in vitro propagation of adult stem cells.

Stem cell maintenance by manipulating signaling pathways: past, current and future

PubMed Central

Chen, Xi; Ye, Shoudong; Ying, Qi-Long

2015-01-01

Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways. [BMB Reports 2015; 48(12): 668-676] PMID:26497581

Stem cells and female reproduction.

PubMed

Du, Hongling; Taylor, Hugh S

2009-02-01

Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent.

The potential of nanofibers in tissue engineering and stem cell therapy.

PubMed

Gholizadeh-Ghaleh Aziz, Shiva; Gholizadeh-Ghaleh Aziz, Sara; Akbarzadeh, Abolfazl

2016-08-01

Electrospinning is a technique in which materials in solution are shaped into continuous nano- and micro-sized fibers. Combining stem cells with biomaterial scaffolds and nanofibers affords a favorable approach for bone tissue engineering, stem cell growth and transfer, ocular surface reconstruction, and treatment of congenital corneal diseases. This review seeks to describe the current examples of the use of scaffolds in stem cell therapy. Stem cells are classified as adult or embryonic stem (ES) cells, and the advantages and drawbacks of each group are detailed. The nanofibers and scaffolds are further classified in Tables I and II , which describe specific examples from the literature. Finally, the current applications of biomaterial scaffolds containing stem cells for tissue engineering applications are presented. Overall, this review seeks to give an overview of the biomaterials available for use in combination with stem cells, and the application of nanofibers in stem cell therapy.

The stem cell patent landscape as relevant to cancer vaccines.

PubMed

Wang, Shyh-Jen

2011-10-01

Cancer vaccine targeting cancer stem cells is proposed to serve as a potent immunotherapy. Thus, it would be useful to examine the main trends in stem cell patenting activity as a guide for those seeking to develop such cancer vaccines. We found that a substantial number of stem cell patents were granted up to the end of 2010, including ~2000 issued in the US. Many of these have been filed since 2001, including 7,551 applications in the US. Stem cell development, as evidenced by the numbers of PubMed articles, has matured steadily in recent years. However, the other metrics, such as the number of patent applications, the technology-science linkage and the number of patent assignees, have been stagnant. Moreover, the ownership of stem cell patents is still quiet fragmented across multiple organizations, and the number of stem cell patent assignees from the business sector has not increased significantly. Academic and nonprofit institutions not only account for a large share of stem cell patents but also apply for patents continually. Based on this analysis, the strength of stem cell resources seems to remain stagnant in recent years due to the ban on government funding of embryonic stem cell research. Furthermore, the patent prosecution or technical barriers in the field of stem cells would be another main reason that the number of US-issued stem cell patents for each application have been in gradual decline since 2000. Therefore, we consider stem cell technology to still be under development.

Fraudsters operate and officialdom turns a blind eye: a proposal for controlling stem cell therapy in China.

PubMed

Jiang, Li; Dong, Bing He

2016-09-01

Stem cell tourism-the flow of patients from home countries to destination countries to obtain stem cell treatment-is a growing business in China. Many concerns have been raised regarding fraudsters that operate unsafe stem cell therapies and an officialdom that turns a blind eye to the questionable technology. The Chinese regulatory approach to stem cell research is based on Guidelines and Administrative Measures, rather than legislation, and may have no binding force on certain institutions, such as military hospitals. There is no liability and traceability system and no visible set of penalties for non-compliance in the stem cell legal framework. In addition to the lack of safety and efficacy systems in the regulations, no specific expert authority has been established to monitor stem cell therapy to date. Recognizing the global nature of stem cell tourism, this article argues that resolving stem cell tourism issues may require not only the Chinese government but also an international mechanism for transparency and ethical oversight. A stringent set of international regulations that govern stem cell therapies can encourage China to improve stem cell regulation and enforcement to fulfill its obligations. Through an international consensus, a minimum standard for clinical stem cell research and a central enforcement system will be provided. As a result, rogue clinics that conduct unauthorized stem cell therapies can be penalized, and countries that are reluctant to implement the reconciled regulations should be sanctioned.

Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

PubMed Central

Beerman, Isabel; Rossi, Derrick J.

2015-01-01

Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

Attitude of A Sample of Iranian Researchers toward The Future of Stem Cell Research.

PubMed

Lotfipanah, Mahdi; Azadeh, Fereydoon; Totonchi, Mehdi; Omani-Samani, Reza

2018-10-01

Stem cells that have unlimited proliferation potential as well as differentiation potency are considered to be a promising future treatment method for incurable diseases. The aim of the present study is to evaluate the future trend of stem cell researches from researchers' viewpoints. This was a cross-sectional descriptive study on researchers involved in stem cell research at Royan Institute. We designed a questionnaire using a qualitative study based on expert opinion and a literature review. Content validity was performed using three rounds of the Delphi method with experts. Face validity was undertaken by a Persian literature expert and a graphics designer. The questionnaire was distributed among 150 researchers involved in stem cell studies in Royan Institute biology laboratories. We collected 138 completed questionnaires. The mean age of participants was 31.13 ± 5.8 years; most (60.9%) were females. Participants (76.1%) considered the budget to be the most important issue in stem cell research, 79.7% needed financial support from the government, and 77.5% felt that charities could contribute substantially to stem cell research. A total of 90.6% of participants stated that stem cells should lead to commercial usage which could support future researches (86.2%). The aim of stem cell research was stipulated as increasing health status of the society according to 92.8% of the participants. At present, among cell types, importance was attached to cord blood and adult stem cells. Researchers emphasized the importance of mesenchymal stem cells (MSCs) rather than hematopoietic stem cells (HSCs, 57.73%). The prime priorities were given to cancer so that stem cell research could be directed to sphere stem cell research whereas the least preference was given to skin research. Regenerative medicine is considered the future of stem cell research with emphasis on application of these cells, especially in cancer treatment. Copyright© by Royan Institute. All rights reserved.

Translating stem cell research: challenges at the research frontier.

PubMed

Magnus, David

2010-01-01

This paper will address the translation of basic stem cell research into clinical research. While "stem cell" trials are sometimes used to describe established practices of bone marrow transplantation or transplantation of primary cells derived from bone marrow, for the purposes of this paper, I am primarily focusing on stem cell trials which are far less established, including use of hESC derived stem cells. The central ethical challenges in stem cell clinical trials arise in frontier research, not in standard, well-established areas of research.

Murine hepatocellular carcinoma derived stem cells reveal epithelial-to-mesenchymal plasticity.

PubMed

Jayachandran, Aparna; Shrestha, Ritu; Dhungel, Bijay; Huang, I-Tao; Vasconcelos, Marianna Yumi Kawashima; Morrison, Brian J; Ramlogan-Steel, Charmaine A; Steel, Jason C

2017-09-26

To establish a model to enrich and characterize stem-like cells from murine normal liver and hepatocellular carcinoma (HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition (EMT). In this study, we utilized a stem cell conditioned serum-free medium to enrich stem-like cells from mouse HCC and normal liver cell lines, Hepa 1-6 and AML12, respectively. We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating the RNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR (qRT-PCR). Next, we examined the relationship between stem cells and EMT using qRT-PCR. Three-dimensional spheres were enriched by culturing murine HCC and normal hepatocyte cell lines in stem cell conditioned serum-free medium supplemented with epidermal growth factor, basic fibroblast growth factor and heparin sulfate. The 3-dimensional spheres had enhanced stemness markers such as Klf4 and Bmi1 and hepatic cancer stem cell (CSC) marker Cd44 compared to parental cells grown as adherent cultures. We report that epithelial markers E-cadherin and ZO-1 were downregulated, while mesenchymal markers Vimentin and Fibronectin were upregulated in 3-dimensional spheres. The 3-dimensional spheres also exhibited changes in expression of Snai , Zeb and Twist family of EMT transcription factors. Our novel method successfully enriched stem-like cells which possessed an EMT phenotype. The isolation and characterization of murine hepatic CSCs could establish a precise target for the development of more effective therapies for HCC.

Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells.

PubMed

Zhang, Zhaocheng; Nör, Felipe; Oh, Min; Cucco, Carolina; Shi, Songtao; Nör, Jacques E

2016-06-01

Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/β-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, β-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/β-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587. © 2016 AlphaMed Press.

MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

PubMed

Zhou, Nan; Hao, Shuang; Huang, Zongqiang; Wang, Weiwei; Yan, Penghui; Zhou, Wei; Zhu, Qihang; Liu, Xiaokang

2018-01-01

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

International Society for Stem Cell Research

MedlinePlus

... cell and regenerative medicine community. More stem cell research Take a closer look Recent Blogs View All ... nonprofit organization & the voice of the stem cell research community The International Society for Stem Cell Research ( ...

Stem cell regenerative potential combined with nanotechnology and tissue engineering for myocardial regeneration.

PubMed

Calin, Manuela; Stan, Daniela; Simion, Viorel

2013-07-01

The stem cell-based therapy for post-infarction myocardial regeneration has been introduced more than a decade ago, but the functional improvement obtained is limited due to the poor retention and short survival rate of transplanted cells into the damaged myocardium. More recently, the emerging nanotechnology concepts for advanced diagnostics and therapy provide promising opportunities of using stem cells for myocardial regeneration. In this paper will be provided an overview of the use of nanotechnology approaches in stem cell research for: 1) cell labeling to track the distribution of stem cells after transplantation, 2) nanoparticle-mediated gene delivery to stem cells to promote their homing, engraftment, survival and differentiation in the ischemic myocardium and 3) obtaining of bio-inspired materials to provide suitable myocardial scaffolds for delivery of stem cells or stem cell-derived factors.

Advances in Bone Marrow Stem Cell Therapy for Retinal Dysfunction

PubMed Central

Park, Susanna S.; Moisseiev, Elad; Bauer, Gerhard; Anderson, Johnathon D.; Grant, Maria B.; Zam, Azhar; Zawadzki, Robert J.; Werner, John S.; Nolta, Jan A.

2016-01-01

The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue. Since the paracrine trophic effects can have regenerative effects on multiple cells in the retina, the use of this cell therapy is not limited to a particular retinal condition. Autologous bone marrow-derived stem cells are being explored in early clinical trials as therapy for various retinal conditions. These bone marrow stem cells include mesenchymal stem cells, mononuclear cells and CD34+ cells. Autologous therapy requires no systemic immunosuppression or donor matching. Intravitreal delivery of CD34+ cells and mononuclear cells appears to be tolerated and is being explored since some of these cells can home into the damaged retina after intravitreal administration. The safety of intravitreal delivery of mesenchymal stem cells has not been well established. This review provides an update of the current evidence in support of the use of bone marrow stem cells as treatment for retinal dysfunction. The potential limitations and complications of using certain forms of bone marrow stem cells as therapy are discussed. Future directions of research include methods to optimize the therapeutic potential of these stem cells, non-cellular alternatives using extracellular vesicles, and in vivo high-resolution retinal imaging to detect cellular changes in the retina following cell therapy. PMID:27784628

Role of stem cell derived exosomes in tumor biology.

PubMed

Sharma, Aman

2018-03-15

Exosomes are nano-scale messengers loaded with bio-molecular cargo of RNA, DNA, and Proteins. As a master regulator of cellular signaling, stem cell (both normal, and cancer stem cells) secreted exosome orchestrate various autocrine and paracrine functions which alter tumor micro-environment, growth and progression. Exosomes secreted by one of the two important stem cell phenotypes in cancers a) Mesenchymal stem cells, and b) Cancer stem cells not only promote cancerous growth but also impart therapy resistance in cancer cells. In tumors, normal or mesenchymal stem cell (MSCs) derived exosomes (MSC-exo) modulate tumor hallmarks by delivering unique miRNA species to neighboring cells and help in tumor progression. Apart from regulating tumor cell fate, MSC-exo are also capable of inducing physiological processes, for example, angiogenesis, metastasis and so forth. Similarly, cancer stem cells (CSCs) derived exosomes (CSC-exo) contain stemness-specific proteins, self-renewal promoting regulatory miRNAs, and survival factors. CSC-exo specific cargo maintains tumor heterogeneity and alters tumor progression. In this review we critically discuss the importance of stem cell specific exosomes in tumor cell signaling pathways with their role in tumor biology. © 2017 UICC.

Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics

NASA Astrophysics Data System (ADS)

Smith, Quinton; Stukalin, Evgeny; Kusuma, Sravanti; Gerecht, Sharon; Sun, Sean X.

2015-07-01

Stem cell differentiation underlies many fundamental processes such as development, tissue growth and regeneration, as well as disease progression. Understanding how stem cell differentiation is controlled in mixed cell populations is an important step in developing quantitative models of cell population dynamics. Here we focus on quantifying the role of cell-cell interactions in determining stem cell fate. Toward this, we monitor stem cell differentiation in adherent cultures on micropatterns and collect statistical cell fate data. Results show high cell fate variability and a bimodal probability distribution of stem cell fraction on small (80-140 μm diameter) micropatterns. On larger (225-500 μm diameter) micropatterns, the variability is also high but the distribution of the stem cell fraction becomes unimodal. Using a stochastic model, we analyze the differentiation dynamics and quantitatively determine the differentiation probability as a function of stem cell fraction. Results indicate that stem cells can interact and sense cellular composition in their immediate neighborhood and adjust their differentiation probability accordingly. Blocking epithelial cadherin (E-cadherin) can diminish this cell-cell contact mediated sensing. For larger micropatterns, cell motility adds a spatial dimension to the picture. Taken together, we find stochasticity and cell-cell interactions are important factors in determining cell fate in mixed cell populations.

NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

PubMed

Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

2012-02-01

Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.

PubMed

Hu, Wen-Yang; Hu, Dan-Ping; Xie, Lishi; Li, Ye; Majumdar, Shyama; Nonn, Larisa; Hu, Hong; Shioda, Toshi; Prins, Gail S

2017-08-01

Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers. Knockdown of KRT13 or PRAC1 reduced sphere formation and symmetric self-renewal highlighting their role in stem cell maintenance. Pathways analysis identified ribosome biogenesis and membrane estrogen-receptor signaling enriched in stem cells with NF-ĸB signaling enriched in progenitors; activities that were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Materials as stem cell regulators

PubMed Central

Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

2014-01-01

The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine. PMID:24845994

Stem cells in genetically-engineered mouse models of prostate cancer

PubMed Central

Shibata, Maho; Shen, Michael M.

2015-01-01

The cancer stem cell model proposes that tumors have a hierarchical organization in which tumorigenic cells give rise to non-tumorigenic cells, with only a subset of stem-like cells able to propagate the tumor. In the case of prostate cancer, recent analyses of genetically engineered mouse (GEM) models have provided evidence supporting the existence of cancer stem cells in vivo. These studies suggest that cancer stem cells capable of tumor propagation exist at various stages of tumor progression from prostatic intraepithelial neoplasia (PIN) to advanced metastatic and castration-resistant disease. However, studies of stem cells in prostate cancer have been limited by available approaches for evaluating their functional properties in cell culture and transplantation assays. Given the role of the tumor microenvironment and the putative cancer stem cell niche, future studies using GEM models to analyze cancer stem cells in their native tissue microenvironment are likely to be highly informative. PMID:26341780

The evolution of chicken stem cell culture methods.

PubMed

Farzaneh, M; Attari, F; Mozdziak, P E; Khoshnam, S E

2017-12-01

1. The avian embryo is an excellent model for studying embryology and the production of pharmaceutical proteins in transgenic chickens. Furthermore, chicken stem cells have the potential for proliferation and differentiation and emerged as an attractive tool for various cell-based technologies. 2. The objective of these studies is the derivation and culture of these stem cells is the production of transgenic birds for recombinant biomaterials and vaccine manufacture, drug and cytotoxicity testing, as well as to gain insight into basic science, including cell tracking. 3. Despite similarities among the established chicken stem cell lines, fundamental differences have been reported between their culture conditions and applications. Recent conventional protocols used for expansion and culture of chicken stem cells mostly depend on feeder cells, serum-containing media and static culture. 4. Utilising chicken stem cells for generation of cell-based transgenic birds and a variety of vaccines requires large-scale cell production. However, scaling up the conventional adherent chicken stem cells is challenging and labour intensive. Development of a suspension cell culture process for chicken embryonic stem cells (cESCs), chicken primordial germ cells (PGCs) and chicken induced pluripotent stem cells (ciPSCs) will be an important advance for increasing the growth kinetics of these cells. 6. This review describes various approaches and suggestions to achieve optimal cell growth for defined chicken stem cells cultures and use in future manufacturing applications.

Development of hematopoietic stem and progenitor cells from human pluripotent stem cells.

PubMed

Chen, Tong; Wang, Fen; Wu, Mengyao; Wang, Zack Z

2015-07-01

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), provide a new cell source for regenerative medicine, disease modeling, drug discovery, and preclinical toxicity screening. Understanding of the onset and the sequential process of hematopoietic cells from differentiated hPSCs will enable the achievement of personalized medicine and provide an in vitro platform for studying of human hematopoietic development and disease. During embryogenesis, hemogenic endothelial cells, a specified subset of endothelial cells in embryonic endothelium, are the primary source of multipotent hematopoietic stem cells. In this review, we discuss current status in the generation of multipotent hematopoietic stem and progenitor cells from hPSCs via hemogenic endothelial cells. We also review the achievements in direct reprogramming from non-hematopoietic cells to hematopoietic stem and progenitor cells. Further characterization of hematopoietic differentiation in hPSCs will improve our understanding of blood development and expedite the development of hPSC-derived blood products for therapeutic purpose. © 2015 Wiley Periodicals, Inc.

Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome

PubMed Central

Tang, Junnan; Shen, Deliang; Caranasos, Thomas George; Wang, Zegen; Vandergriff, Adam C.; Allen, Tyler A.; Hensley, Michael Taylor; Dinh, Phuong-Uyen; Cores, Jhon; Li, Tao-Sheng; Zhang, Jinying; Kan, Quancheng; Cheng, Ke

2017-01-01

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell–cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration. PMID:28045024

Stem cell plasticity enables hair regeneration following Lgr5+ cell loss.

PubMed

Hoeck, Joerg D; Biehs, Brian; Kurtova, Antonina V; Kljavin, Noelyn M; de Sousa E Melo, Felipe; Alicke, Bruno; Koeppen, Hartmut; Modrusan, Zora; Piskol, Robert; de Sauvage, Frederic J

2017-06-01

Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5 + (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5 + cells in mice abrogates hair regeneration but this is reversible. During recovery, CD34 + (CD34 antigen) stem cells activate inflammatory response programs and start dividing. Pharmacological attenuation of inflammation inhibits CD34 + cell proliferation. Subsequently, the Wnt pathway controls the recovery of Lgr5 + cells and inhibition of Wnt signalling prevents Lgr5 + cell and hair germ recovery. Thus, our study uncovers a compensatory relationship between two stem cell populations and the underlying molecular mechanisms that enable hair follicle regeneration.

SILAC proteomics of planarians identifies Ncoa5 as a conserved component of pluripotent stem cells.

PubMed

Böser, Alexander; Drexler, Hannes C A; Reuter, Hanna; Schmitz, Henning; Wu, Guangming; Schöler, Hans R; Gentile, Luca; Bartscherer, Kerstin

2013-11-27

Planarian regeneration depends on the presence of pluripotent stem cells in the adult. We developed an in vivo stable isotope labeling by amino acids in cell culture (SILAC) protocol in planarians to identify proteins that are enriched in planarian stem cells. Through a comparison of SILAC proteomes of normal and stem cell-depleted planarians and of a stem cell-enriched population of sorted cells, we identified hundreds of stem cell proteins. One of these is an ortholog of nuclear receptor coactivator-5 (Ncoa5/CIA), which is known to regulate estrogen-receptor-mediated transcription in human cells. We show that Ncoa5 is essential for the maintenance of the pluripotent stem cell population in planarians and that a putative mouse ortholog is expressed in pluripotent cells of the embryo. Our study thus identifies a conserved component of pluripotent stem cells, demonstrating that planarians, in particular, when combined with in vivo SILAC, are a powerful model in stem cell research. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Stem cells in reproductive medicine: ready for the patient?

PubMed

Vassena, R; Eguizabal, C; Heindryckx, B; Sermon, K; Simon, C; van Pelt, A M M; Veiga, A; Zambelli, F

2015-09-01

Are there effective and clinically validated stem cell-based therapies for reproductive diseases? At the moment, clinically validated stem cell treatments for reproductive diseases and alterations are not available. Research in stem cells and regenerative medicine is growing in scope, and its translation to the clinic is heralded by the recent initiation of controlled clinical trials with pluripotent derived cells. Unfortunately, stem cell 'treatments' are currently offered to patients outside of the controlled framework of scientifically sound research and regulated clinical trials. Both physicians and patients in reproductive medicine are often unsure about stem cells therapeutic options. An international working group was assembled to review critically the available scientific literature in both the human species and animal models. This review includes work published in English until December 2014, and available through Pubmed. A few areas of research in stem cell and reproductive medicine were identified: in vitro gamete production, endometrial regeneration, erectile dysfunction amelioration, vaginal reconstruction. The stem cells studied range from pluripotent (embryonic stem cells and induced pluripotent stem cells) to monopotent stem cells, such as spermatogonial stem cells or mesenchymal stem cells. The vast majority of studies have been carried out in animal models, with data that are preliminary at best. This review was not conducted in a systematic fashion, and reports in publications not indexed in Pubmed were not analyzed. A much broader clinical knowledge will have to be acquired before translation to the clinic of stem cell therapies in reproductive medicine; patients and physicians should be wary of unfounded claims of improvement of existing medical conditions; at the moment, effective stem cell treatment for reproductive diseases and alterations is not available. None. NA. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Distinct roles of neuroepithelial-like and radial glia-like progenitor cells in cerebellar regeneration.

PubMed

Kaslin, Jan; Kroehne, Volker; Ganz, Julia; Hans, Stefan; Brand, Michael

2017-04-15

Zebrafish can regenerate after brain injury, and the regenerative process is driven by resident stem cells. Stem cells are heterogeneous in the vertebrate brain, but the significance of having heterogeneous stem cells in regeneration is not understood. Limited availability of specific stem cells might impair the regeneration of particular cell lineages. We studied regeneration of the adult zebrafish cerebellum, which contains two major stem and progenitor cell types: ventricular zone and neuroepithelial cells. Using conditional lineage tracing we demonstrate that cerebellar regeneration depends on the availability of specific stem cells. Radial glia-like cells are thought to be the predominant stem cell type in homeostasis and after injury. However, we find that radial glia-like cells play a minor role in adult cerebellar neurogenesis and in recovery after injury. Instead, we find that neuroepithelial cells are the predominant stem cell type supporting cerebellar regeneration after injury. Zebrafish are able to regenerate many, but not all, cell types in the cerebellum, which emphasizes the need to understand the contribution of different adult neural stem and progenitor cell subtypes in the vertebrate central nervous system. © 2017. Published by The Company of Biologists Ltd.

Role of the Stem Cell Niche in Hormone-induced Tumorigenesis in Fetal Mouse Mammary Epithelium

DTIC Science & Technology

2006-08-01

Develop an immunohistochemical method for identifying stem cells and stem cell niches, and to use this to determine if in utero estrogenic...overstimulation causes changes in the number of stem cells or their niches. To extend the power of ex vivo stem cell isolation and enumeration by providing a...marginal success due primarily to 1) most antibodies previously reputed to be stem cell specific turned out to be present in differentiated mammary

Wnt and BMP Signaling Crosstalk in Regulating Dental Stem Cells: Implications in Dental Tissue Engineering

PubMed Central

Zhang, Fugui; Song, Jinglin; Zhang, Hongmei; Huang, Enyi; Song, Dongzhe; Tollemar, Viktor; Wang, Jing; Wang, Jinhua; Mohammed, Maryam; Wei, Qiang; Fan, Jiaming; Liao, Junyi; Zou, Yulong; Liu, Feng; Hu, Xue; Qu, Xiangyang; Chen, Liqun; Yu, Xinyi; Luu, Hue H.; Lee, Michael J.; He, Tong-Chuan; Ji, Ping

2016-01-01

Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling. Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance, essential oral functions and the quality of life. Regenerative dentistry holds great promise in treating oral/dental disorders. The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells, along with the signaling mechanisms governing stem cell self-renewal and differentiation. In this review, we first summarize the biological characteristics of seven types of dental stem cells, including dental pulp stem cells, stem cells from apical papilla, stem cells from human exfoliated deciduous teeth, dental follicle precursor cells, periodontal ligament stem cells, alveolar bone-derived mesenchymal stem cells (MSCs), and MSCs from gingiva. We then focus on how these stem cells are regulated by bone morphogenetic protein (BMP) and/or Wnt signaling by examining the interplays between these pathways. Lastly, we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways. We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications. Thus, we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade. PMID:28491933

Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

PubMed

Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

2018-03-27

Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

Knowledge and Attitude about Stem Cells and Their Application in Medicine among Nursing Students in Universiti Sains Malaysia, Malaysia

PubMed Central

LYE, Jee Leng; SOON, Lean Keng; WAN AHMAD, Wan Amir Nizam; TAN, Suat Cheng

2015-01-01

Background: Stem cell research has been extensively explored worldwide to enhance human health in medical setting. Nevertheless, there is currently no full understanding of the stem cell knowledge and attitude levels among student nurses in Malaysia. This study aimed to assess the level of stem cell knowledge, attitude toward stem cell application in medicine, and its association with years of education, among Universiti Sains Malaysia (USM) undergraduate nursing students. Methods: A cross-sectional study (n = 88) was conducted using self-administered questionnaire consisted of demographic information, stem cells knowledge and attitude statements. Data was analysed using Statistical Package Social Software 20.0. Results: The majority of participants (92%) had moderate knowledge score about stem cells. Many students (33%) worried that stem cell application might cause a harm to humanity yet had a positive (76.1%) attitude towards its therapeutic potential (45.5%). Poor correlation between knowledge and attitude (r = 0.08) indicated that acceptance towards stem cell is not solely based on the knowledge level but also on other factors including religion and culture. Conclusion: Therefore, this study suggests that various educational programs on stem cell should be implemented considering the religion, cultural, social, and behavioural determinants in the population to improve stem cell knowledge and encourage a more positive attitude towards stem cells in medicine among these nursing students. PMID:26715905

Knowledge and Attitude about Stem Cells and Their Application in Medicine among Nursing Students in Universiti Sains Malaysia, Malaysia.

PubMed

Lye, Jee Leng; Soon, Lean Keng; Wan Ahmad, Wan Amir Nizam; Tan, Suat Cheng

2015-01-01

Stem cell research has been extensively explored worldwide to enhance human health in medical setting. Nevertheless, there is currently no full understanding of the stem cell knowledge and attitude levels among student nurses in Malaysia. This study aimed to assess the level of stem cell knowledge, attitude toward stem cell application in medicine, and its association with years of education, among Universiti Sains Malaysia (USM) undergraduate nursing students. A cross-sectional study (n = 88) was conducted using self-administered questionnaire consisted of demographic information, stem cells knowledge and attitude statements. Data was analysed using Statistical Package Social Software 20.0. The majority of participants (92%) had moderate knowledge score about stem cells. Many students (33%) worried that stem cell application might cause a harm to humanity yet had a positive (76.1%) attitude towards its therapeutic potential (45.5%). Poor correlation between knowledge and attitude (r = 0.08) indicated that acceptance towards stem cell is not solely based on the knowledge level but also on other factors including religion and culture. Therefore, this study suggests that various educational programs on stem cell should be implemented considering the religion, cultural, social, and behavioural determinants in the population to improve stem cell knowledge and encourage a more positive attitude towards stem cells in medicine among these nursing students.

Stem cell motility enables a density-dependent rate of fate commitment during scaled resizing of adult organs

NASA Astrophysics Data System (ADS)

Du, Xinxin; O'Brien, Lucy; Riedel-Kruse, Ingmar

Many adult organs grow or shrink to accommodate fluctuating levels of physiological demand. Specifically, the intestine of the fruit fly (the midgut) expands four-fold in the number of mature cells and, proportionally, the number of stem cells when the fly eats. However, the cellular behaviors that give rise to this stem scaling are not well-understood. Here we present a biophysical model of the adult fly midgut. A set of differential equations can recapitulate the physiological kinetics of cells during midgut growth and shrinkage as long as the rate of stem cell fate commitment depends on the stem cell number density in the tissue. To elucidate the source of this dependence, we model the tissue in a 2D simulation with soft spheres, where stem cells choose fate commitment through Delta-Notch pathway interactions with other stem cells, a known process in fly midguts. We find that as long as stem cells exhibit a large enough amplitude of random motion through the tissue (`stem cell motility'), and explore a large enough `territory' in their lifetime, stem cell scaling can occur. These model observations are confirmed through in vivo live-imaging, where we indeed see that stem cells are motile in the fly midgut.

Ethics and Policy Issues for Stem Cell Research and Pulmonary Medicine

PubMed Central

Lowenthal, Justin

2015-01-01

Stem cell research and related initiatives in regenerative medicine, cell-based therapy, and tissue engineering have generated considerable scientific and public interest. Researchers are applying stem cell technologies to chest medicine in a variety of ways: using stem cells as models for drug discovery, testing stem cell-based therapies for conditions as diverse as COPD and cystic fibrosis, and producing functional lung and tracheal tissue for physiologic modeling and potential transplantation. Although significant scientific obstacles remain, it is likely that stem cell-based regenerative medicine will have a significant clinical impact in chest medicine. However, stem cell research has also generated substantial controversy, posing a variety of ethical and regulatory challenges for research and clinical practice. Some of the most prominent ethical questions related to the use of stem cell technologies in chest medicine include (1) implications for donors, (2) scientific prerequisites for clinical testing and use, (3) stem cell tourism, (4) innovation and clinical use of emerging stem cell-based interventions, (5) responsible translation of stem cell-based therapies to clinical use, and (6) appropriate and equitable access to emerging therapies. Having a sense of these issues should help to put emerging scientific advances into appropriate context and to ensure the responsible clinical translation of promising therapeutics. PMID:25732448

A Survey of Italian Physicians' Opinion about Stem Cells Research: What Doctors Prefer and What the Law Requires

PubMed Central

Frati, Paola; Pacchiarotti, Arianna; D'Errico, Stefano

2014-01-01

To evaluate the Italian physicians' knowledge/information level about the therapeutic potential of stem cells, the research choice between embryonic and cordonal stem cells, and the preference between autologous and heterologous storage of cordonal stem cells, we performed a national survey. The questionnaire—distributed to 3361 physicians—involved physicians of different religious orientations and of different medical specialities. Most of the physicians involved (67%) were Catholics, and the majority were gynaecologists and paediatricians (43%) who are mainly in charge to inform future mothers about the possibility of cordonal stem cells conservation. The majority of the physicians interviewed do not have specific knowledge about stem cells (59%), most of them having only generic information (92%). The largest part of physicians prefer to use umbilical cord blood cells rather than embryonic stem cells. Nevertheless, a large percentage of physicians were in favour of embryo research, especially when embryos are supernumerary (44% versus 34%). Eighty-seven % of the physicians interviewed proved to have a general knowledge about stem cells and believe in their therapeutic potential. They prefer research on cordonal stem cells rather than on embryo stem cells. Although they are in favour of heterologous stem cells donation, they still prefer cryopreservation for personal use. PMID:24877099

Ethics and policy issues for stem cell research and pulmonary medicine.

PubMed

Lowenthal, Justin; Sugarman, Jeremy

2015-03-01

Stem cell research and related initiatives in regenerative medicine, cell-based therapy, and tissue engineering have generated considerable scientific and public interest. Researchers are applying stem cell technologies to chest medicine in a variety of ways: using stem cells as models for drug discovery, testing stem cell-based therapies for conditions as diverse as COPD and cystic fibrosis, and producing functional lung and tracheal tissue for physiologic modeling and potential transplantation. Although significant scientific obstacles remain, it is likely that stem cell-based regenerative medicine will have a significant clinical impact in chest medicine. However, stem cell research has also generated substantial controversy, posing a variety of ethical and regulatory challenges for research and clinical practice. Some of the most prominent ethical questions related to the use of stem cell technologies in chest medicine include (1) implications for donors, (2) scientific prerequisites for clinical testing and use, (3) stem cell tourism, (4) innovation and clinical use of emerging stem cell-based interventions, (5) responsible translation of stem cell-based therapies to clinical use, and (6) appropriate and equitable access to emerging therapies. Having a sense of these issues should help to put emerging scientific advances into appropriate context and to ensure the responsible clinical translation of promising therapeutics.

Propagation of human spermatogonial stem cells in vitro.

PubMed

Sadri-Ardekani, Hooman; Mizrak, Sefika C; van Daalen, Saskia K M; Korver, Cindy M; Roepers-Gajadien, Hermien L; Koruji, Morteza; Hovingh, Suzanne; de Reijke, Theo M; de la Rosette, Jean J M C H; van der Veen, Fulco; de Rooij, Dirk G; Repping, Sjoerd; van Pelt, Ans M M

2009-11-18

Young boys treated with high-dose chemotherapy are often confronted with infertility once they reach adulthood. Cryopreserving testicular tissue before chemotherapy and autotransplantation of spermatogonial stem cells at a later stage could theoretically allow for restoration of fertility. To establish in vitro propagation of human spermatogonial stem cells from small testicular biopsies to obtain an adequate number of cells for successful transplantation. Study performed from April 2007 to July 2009 using testis material donated by 6 adult men who underwent orchidectomy as part of prostate cancer treatment. Testicular cells were isolated and cultured in supplemented StemPro medium; germline stem cell clusters that arose were subcultured on human placental laminin-coated dishes in the same medium. Presence of spermatogonia was determined by reverse transcriptase polymerase chain reaction and immunofluorescence for spermatogonial markers. To test for the presence of functional spermatogonial stem cells in culture, xenotransplantation to testes of immunodeficient mice was performed, and migrated human spermatogonial stem cells after transplantation were detected by COT-1 fluorescence in situ hybridization. The number of colonized spermatogonial stem cells transplanted at early and later points during culture were counted to determine propagation. Propagation of spermatogonial stem cells over time. Testicular cells could be cultured and propagated up to 15 weeks. Germline stem cell clusters arose in the testicular cell cultures from all 6 men and could be subcultured and propagated up to 28 weeks. Expression of spermatogonial markers on both the RNA and protein level was maintained throughout the entire culture period. In 4 of 6 men, xenotransplantation to mice demonstrated the presence of functional spermatogonial stem cells, even after prolonged in vitro culture. Spermatogonial stem cell numbers increased 53-fold within 19 days in the testicular cell culture and increased 18,450-fold within 64 days in the germline stem cell subculture. Long-term culture and propagation of human spermatogonial stem cells in vitro is achievable.

Stem cell technology for drug discovery and development.

PubMed

Hook, Lilian A

2012-04-01

Stem cells have enormous potential to revolutionise the drug discovery process at all stages, from target identification through to toxicology studies. Their ability to generate physiologically relevant cells in limitless supply makes them an attractive alternative to currently used recombinant cell lines or primary cells. However, realisation of the full potential of stem cells is currently hampered by the difficulty in routinely directing stem cell differentiation to reproducibly and cost effectively generate pure populations of specific cell types. In this article we discuss how stem cells have already been used in the drug discovery process and how novel technologies, particularly in relation to stem cell differentiation, can be applied to attain widespread adoption of stem cell technology by the pharmaceutical industry. Copyright © 2011 Elsevier Ltd. All rights reserved.

College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

NASA Astrophysics Data System (ADS)

Concannon, James P.; Siegel, Marcelle A.; Halverson, Kristy; Freyermuth, Sharyn

2010-04-01

In this study, we examined 96 undergraduate non-science majors' conceptions of stem cells, stem cell research, and cloning. This study was performed at a large, Midwest, research extensive university. Participants in the study were asked to answer 23 questions relating to stem cells, stem cell research, and cloning in an on-line assessment before and after instruction. Two goals of the instruction were to: (1) help students construct accurate scientific ideas, and (2) enhance their reasoning about socioscientific issues. The course structure included interactive lectures, case discussions, hands-on activities, and independent projects. Overall, students' understandings of stem cells, stem cell research, and cloning increased from pre-test to post-test. For example, on the post-test, students gained knowledge concerning the age of an organism related to the type of stem cell it possesses. However, we found that some incorrect ideas that were evident on the pre-test persisted after instruction. For example, before and after instruction several students maintained the idea that stem cells can currently be used to produce organs.

Advances and Prospects in Stem Cells for Cartilage Regeneration

PubMed Central

Wang, Mingjie; Yuan, Zhiguo; Ma, Ning; Hao, Chunxiang; Guo, Weimin; Zou, Gengyi; Zhang, Yu; Chen, Mingxue; Gao, Shuang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Lu, Shibi

2017-01-01

The histological features of cartilage call attention to the fact that cartilage has a little capacity to repair itself owing to the lack of a blood supply, nerves, or lymphangion. Stem cells have emerged as a promising option in the field of cartilage tissue engineering and regenerative medicine and could lead to cartilage repair. Much research has examined cartilage regeneration utilizing stem cells. However, both the potential and the limitations of this procedure remain controversial. This review presents a summary of emerging trends with regard to using stem cells in cartilage tissue engineering and regenerative medicine. In particular, it focuses on the characterization of cartilage stem cells, the chondrogenic differentiation of stem cells, and the various strategies and approaches involving stem cells that have been used in cartilage repair and clinical studies. Based on the research into chondrocyte and stem cell technologies, this review discusses the damage and repair of cartilage and the clinical application of stem cells, with a view to increasing our systematic understanding of the application of stem cells in cartilage regeneration; additionally, several advanced strategies for cartilage repair are discussed. PMID:28246531

Stem Cell-Derived Exosome in Cardiovascular Diseases: Macro Roles of Micro Particles.

PubMed

Yuan, Ye; Du, Weijie; Liu, Jiaqi; Ma, Wenya; Zhang, Lai; Du, Zhimin; Cai, Benzhi

2018-01-01

The stem cell-based therapy has emerged as the promising therapeutic strategies for cardiovascular diseases (CVDs). Recently, increasing evidence suggest stem cell-derived active exosomes are important communicators among cells in the heart via delivering specific substances to the adjacent/distant target cells. These exosomes and their contents such as certain proteins, miRNAs and lncRNAs exhibit huge beneficial effects on preventing heart damage and promoting cardiac repair. More importantly, stem cell-derived exosomes are more effective and safer than stem cell transplantation. Therefore, administration of stem cell-derived exosomes will expectantly be an alternative stem cell-based therapy for the treatment of CVDs. Furthermore, modification of stem cell-derived exosomes or artificial synthesis of exosomes will be the new therapeutic tools for CVDs in the future. In addition, stem cell-derived exosomes also have been implicated in the diagnosis and prognosis of CVDs. In this review, we summarize the current advances of stem cell-derived exosome-based treatment and prognosis for CVDs, including their potential benefits, underlying mechanisms and limitations, which will provide novel insights of exosomes as a new tool in clinical therapeutic translation in the future.

Stem cells and reproduction.

PubMed

Du, Hongling; Taylor, Hugh S

2010-06-01

To review the latest developments in reproductive tract stem cell biology. In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cryopreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent.

Biliary tract cancer stem cells - translational options and challenges

PubMed Central

Mayr, Christian; Ocker, Matthias; Ritter, Markus; Pichler, Martin; Neureiter, Daniel; Kiesslich, Tobias

2017-01-01

Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells - the cancer stem cells - possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells. PMID:28465631

Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging

PubMed Central

Panich, Uraiwan; Sittithumcharee, Gunya; Rathviboon, Natwarath

2016-01-01

Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been linked to impaired skin homeostasis (e.g., skin premature aging and skin cancers). Skin stem cells, with self-renewal capability and multipotency, are frequently affected by environment. Ultraviolet radiation (UVR), a major cause of stem cell DNA damage, can contribute to depletion of stem cells (ESCs and mesenchymal stem cells) and damage of stem cell niche, eventually leading to photoinduced skin aging. In this review, we discuss the role of UV-induced DNA damage and oxidative stress in the skin stem cell aging in order to gain insights into the pathogenesis and develop a way to reduce photoaging of skin cells. PMID:27148370

Identification of Metastatic Tumor Stem Cell

DTIC Science & Technology

2010-09-01

addition to a tumor stem cell , an existence of a metastatic stem cell is predicted. Despite the critical importance of the concept, this idea has not been...isolating stem cell population from a unique set of breast tumor cell lines and by examining their metastatic behavior in an animal model. The overall...will (i) isolate stem - cell population from non-metastatic and metastatic cells of a pair of syngenic breast tumor cell lines, and test their metastatic

Roles of neural stem cells in the repair of peripheral nerve injury.

PubMed

Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

2017-12-01

Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

Day-night cycles and the sleep-promoting factor, Sleepless, affect stem cell activity in the Drosophila testis.

PubMed

Tulina, Natalia M; Chen, Wen-Feng; Chen, Jung Hsuan; Sowcik, Mallory; Sehgal, Amita

2014-02-25

Adult stem cells maintain tissue integrity and function by renewing cellular content of the organism through regulated mitotic divisions. Previous studies showed that stem cell activity is affected by local, systemic, and environmental cues. Here, we explore a role of environmental day-night cycles in modulating cell cycle progression in populations of adult stem cells. Using a classic stem cell system, the Drosophila spermatogonial stem cell niche, we reveal daily rhythms in division frequencies of germ-line and somatic stem cells that act cooperatively to produce male gametes. We also examine whether behavioral sleep-wake cycles, which are driven by the environmental day-night cycles, regulate stem cell function. We find that flies lacking the sleep-promoting factor Sleepless, which maintains normal sleep in Drosophila, have increased germ-line stem cell (GSC) division rates, and this effect is mediated, in part, through a GABAergic signaling pathway. We suggest that alterations in sleep can influence the daily dynamics of GSC divisions.

IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells.

PubMed

Bie, Qingli; Zhang, Bin; Sun, Caixia; Ji, Xiaoyun; Barnie, Prince Amoah; Qi, Chen; Peng, Jingjing; Zhang, Danyi; Zheng, Dong; Su, Zhaoliang; Wang, Shengjun; Xu, Huaxi

2017-03-21

Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.

A Phenotype-Based RNAi Screening for Ras-ERK/MAPK Signaling-Associated Stem Cell Regulators in C. elegans.

PubMed

Lee, Myon-Hee; Yoon, Dong Suk

2017-01-01

Stem cells have the ability to self-renew and to generate differentiated cell types. A regulatory network that controls this balance is critical for stem cell homeostasis and normal animal development. Particularly, Ras-ERK/MAPK signaling pathway is critical for stem cell self-renewal and differentiation in mammals, including humans. Aberrant regulation of Ras-ERK/MAPK signaling pathway results in either stem cell or overproliferation. Therefore, the identification of Ras-ERK/MAPK signaling pathway-associated regulators is critical to understand the mechanism of stem cell (possibly cancer stem cell) control. In this report, using the nematode C. elegans mutants, we developed a methodology for a phenotype-based RNAi screening that identifies stem cell regulator genes associated with Ras-ERK/MAPK signaling within the context of a whole organism. Importantly, this phenotype-based RNAi screening can be applied for other stem cell-associated signaling pathways such as Wnt/β-catenin and Notch using the C. elegans.

Adipose-derived mesenchymal stem cells and regenerative medicine.

PubMed

Konno, Masamitsu; Hamabe, Atsushi; Hasegawa, Shinichiro; Ogawa, Hisataka; Fukusumi, Takahito; Nishikawa, Shimpei; Ohta, Katsuya; Kano, Yoshihiro; Ozaki, Miyuki; Noguchi, Yuko; Sakai, Daisuke; Kudoh, Toshihiro; Kawamoto, Koichi; Eguchi, Hidetoshi; Satoh, Taroh; Tanemura, Masahiro; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

2013-04-01

Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

A dual role of p21 in stem cell aging.

PubMed

Ju, Zhenyu; Choudhury, Aaheli Roy; Rudolph, K Lenhard

2007-04-01

A decline in adult stem cell function occurs during aging, likely contributing to the decline in organ homeostasis and regeneration with age. An emerging field in aging research is to analyze molecular pathways limiting adult stem cell function in response to macromolecular damage accumulation during aging. Current data suggest that the p21 cell cycle inhibitor has a dual role in stem cell aging: On one hand, p21 protects adult stem cells from acute genotoxic stress by preventing inappropriate cycling of acutely damaged stem cells. On the other hand, p21 activation impairs stem cell function and survival of aging telomere dysfunctional mice indicating that p21 checkpoint function is disadvantageous in the context of chronic and persistent damage, which accumulates during aging. This article focuses on these dual roles of p21 in aging stem cells.

Stem Cell Pathology.

PubMed

Fu, Dah-Jiun; Miller, Andrew D; Southard, Teresa L; Flesken-Nikitin, Andrea; Ellenson, Lora H; Nikitin, Alexander Yu

2018-01-24

Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Therefore, there is an urgent need for developing stem cell pathology as a discipline to facilitate stem cell research and regenerative medicine. This review provides examples of anatomically defined niches suitable for evaluation by diagnostic pathologists, describes neoplastic lesions associated with them, and discusses further directions of stem cell pathology.

The clinical use of regenerative therapy in COPD

PubMed Central

Lipsi, Roberto; Rogliani, Paola; Calzetta, Luigino; Segreti, Andrea; Cazzola, Mario

2014-01-01

Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation. PMID:25548520

Plant stem cell niches.

PubMed

Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

2012-01-01

Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.

PubMed

Sampath, Srinath C; Sampath, Srihari C; Ho, Andrew T V; Corbel, Stéphane Y; Millstone, Joshua D; Lamb, John; Walker, John; Kinzel, Bernd; Schmedt, Christian; Blau, Helen M

2018-04-18

The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identifies Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent inducer of muscle stem cell (MuSC, satellite cell) quiescence. OSM is produced by muscle fibers, induces reversible MuSC cell cycle exit, and maintains stem cell regenerative capacity as judged by serial transplantation. Conditional OSM receptor deletion in satellite cells leads to stem cell depletion and impaired regeneration following injury. These results identify Oncostatin M as a secreted niche factor responsible for quiescence induction, and for the first time establish a direct connection between induction of quiescence, stemness, and transplantation potential in solid organ stem cells.

Nuclear Mechanics and Stem Cell Differentiation.

PubMed

Mao, Xinjian; Gavara, Nuria; Song, Guanbin

2015-12-01

Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

Parthenogenesis-derived Multipotent Stem Cells Adapted for Tissue Engineering Applications

PubMed Central

Koh, Chester J.; Delo, Dawn M.; Lee, Jang Won; Siddiqui, M. Minhaj; Lanza, Robert P.; Soker, Shay; Yoo, James J.; Atala, Anthony

2009-01-01

Embryonic stem cells are envisioned as a viable source of pluripotent cells for use in regenerative medicine applications when donor tissue is not available. However, most current harvest techniques for embryonic stem cells require the destruction of embryos, which has led to significant political and ethical limitations on their usage. Parthenogenesis, the process by which an egg can develop into an embryo in the absence of sperm, may be a potential source of embryonic stem cells that may avoid some of the political and ethical concerns surrounding embryonic stem cells. Here we provide the technical aspects of embryonic stem cell isolation and expansion from the parthenogenetic activation of oocytes. These cells were characterized for their stem-cell properties. In addition, these cells were induced to differentiate to the myogenic, osteogenic, adipogenic, and endothelial lineages, and were able to form muscle-like and bony-like tissue in vivo. Furthermore, parthenogenetic stem cells were able to integrate into injured muscle tissue. Together, these results demonstrate that parthenogenetic stem cells can be successfully isolated and utilized for various tissue engineering applications. PMID:18799133

The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity.

PubMed

Campbell, Clinton J V; Lee, Jung Bok; Levadoux-Martin, Marilyne; Wynder, Tracy; Xenocostas, Anargyros; Leber, Brian; Bhatia, Mickie

2010-09-02

The molecular basis for the unique proliferative and self-renewal properties that hierarchically distinguish human stem cells from progenitors and terminally differentiated cells remains largely unknown. We report a role for the Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) as an indispensable regulator of self-renewal in human stem cells and show that a functional dependence on Mcl-1 defines the human stem cell hierarchy. In vivo pharmacologic targeting of the Bcl-2 family members in human hematopoietic stem cells (HSCs) and human leukemic stem cells reduced stem cell regenerative and self-renewal function. Subsequent protein expression studies showed that, among the Bcl-2 family members, only Mcl-1 was up-regulated exclusively in the human HSC fraction on in vivo regeneration of hematopoiesis. Short hairpin RNA-knockdown of Mcl-1 in human cord blood cells did not affect survival in the HSC or hematopoietic progenitor cell fractions in vitro but specifically reduced the in vivo self-renewal function of human HSCs. Moreover, knockdown of Mcl-1 in ontogenetically primitive human pluripotent stem cells resulted in almost complete ablation of stem cell self-renewal function. Our findings show that Mcl-1 is an essential regulator of stem cell self-renewal in humans and therefore represents an axis for therapeutic interventions.

Fake news portrayals of stem cells and stem cell research.

PubMed

Marcon, Alessandro R; Murdoch, Blake; Caulfield, Timothy

2017-10-01

This study examines how stem cells and stem cell research are portrayed on websites deemed to be purveyors of distorted and dubious information. Content analysis was conducted on 224 articles from 2015 to 2016, compiled by searching with the keywords 'stem cell(s)' on a list of websites flagged for containing either 'fake' or 'junk science' news. Articles contained various exaggerated positive and negative claims about stem cells and stem cell science, health and science related conspiracy theories, and statements promoting fear and mistrust of conventional medicine. Findings demonstrate the existence of organized misinformation networks, which may lead the public away from accurate information and facilitate a polarization of public discourse.

Skin appendage-derived stem cells: cell biology and potential for wound repair.

PubMed

Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

2016-01-01

Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundamental characteristics, their preferentially expressed biomarkers, and their potential contribution involved in wound repair. Finally, we will also discuss current strategies, future applications, and limitations of these stem cells, attempting to provide some perspectives on optimizing the available therapy in cutaneous repair and regeneration.

Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

PubMed

Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

2016-07-01

First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835. © 2016 AlphaMed Press.

Basic Science and Clinical Application of Stem Cells in Veterinary Medicine

NASA Astrophysics Data System (ADS)

Ribitsch, I.; Burk, J.; Delling, U.; Geißler, C.; Gittel, C.; Jülke, H.; Brehm, W.

Stem cells play an important role in veterinary medicine in different ways. Currently several stem cell therapies for animal patients are being developed and some, like the treatment of equine tendinopathies with mesenchymal stem cells (MSCs), have already successfully entered the market. Moreover, animal models are widely used to study the properties and potential of stem cells for possible future applications in human medicine. Therefore, in the young and emerging field of stem cell research, human and veterinary medicine are intrinsically tied to one another. Many of the pioneering innovations in the field of stem cell research are achieved by cooperating teams of human and veterinary medical scientists.

CD34+ Testicular Stromal Cells Support Long-Term Expansion of Embryonic and Adult Stem and Progenitor Cells

PubMed Central

Kim, Jiyeon; Seandel, Marco; Falciatori, Ilaria; Wen, Duancheng; Rafii, Shahin

2010-01-01

Stem cells reside in specialized microenvironments created by supporting stromal cells that orchestrate self-renewal and lineage-specific differentiation. However, the precise identity of the cellular and molecular pathways that support self-renewal of stem cells is not known. For example, long-term culture of prototypical stem cells, such as adult spermatogonial stem and progenitor cells (SPCs), in vitro has been impeded by the lack of an optimal stromal cell line that initiates and sustains proliferation of these cells. Indeed, current methods, including the use of mouse embryonic fibroblasts (MEFs), have not been efficient and have generally led to inconsistent results. Here, we report the establishment of a novel CD34-positive cell line, referred to as JK1, derived from mouse testicular stromal cells that not only facilitated long-term SPC culture but also allowed faithful generation of SPCs and multipotent stem cells. SPCs generated on JK1 maintained key features of germ line stem cells, including expression of PLZF, DAZL, and GCNA. Furthermore, these feeders also promoted the long-term cultivation of other types of primitive cells including multi-potent adult spermatogonial-derived stem cells, pluripotent murine embryonic stem cells, and embryonic germ cells derived from primordial germ cells. Stem cells could be passaged serially and still maintained expression of characteristic markers such as OCT4 and NANOG in vitro, as well as the ability to generate all three germ layers in vivo. These results indicate that the JK1 cell line is capable of promoting long-term culture of primitive cells. As such, this cell line allows for identification of stromal-derived factors that support long-term proliferation of various types of stem cells and constitutes a convenient alternative to other types of feeder layers. PMID:18669907