Sample records for stem cells couples

  1. G Protein-Coupled Receptor Signaling in Stem Cells and Cancer.

    PubMed

    Lynch, Jennifer R; Wang, Jenny Yingzi

    2016-05-11

    G protein-coupled receptors (GPCRs) are a large superfamily of cell-surface signaling proteins that bind extracellular ligands and transduce signals into cells via heterotrimeric G proteins. GPCRs are highly tractable drug targets. Aberrant expression of GPCRs and G proteins has been observed in various cancers and their importance in cancer stem cells has begun to be appreciated. We have recently reported essential roles for G protein-coupled receptor 84 (GPR84) and G protein subunit Gαq in the maintenance of cancer stem cells in acute myeloid leukemia. This review will discuss how GPCRs and G proteins regulate stem cells with a focus on cancer stem cells, as well as their implications for the development of novel targeted cancer therapies.

  2. G Protein-Coupled Receptor Signaling in Stem Cells and Cancer

    PubMed Central

    Lynch, Jennifer R.; Wang, Jenny Yingzi

    2016-01-01

    G protein-coupled receptors (GPCRs) are a large superfamily of cell-surface signaling proteins that bind extracellular ligands and transduce signals into cells via heterotrimeric G proteins. GPCRs are highly tractable drug targets. Aberrant expression of GPCRs and G proteins has been observed in various cancers and their importance in cancer stem cells has begun to be appreciated. We have recently reported essential roles for G protein-coupled receptor 84 (GPR84) and G protein subunit Gαq in the maintenance of cancer stem cells in acute myeloid leukemia. This review will discuss how GPCRs and G proteins regulate stem cells with a focus on cancer stem cells, as well as their implications for the development of novel targeted cancer therapies. PMID:27187360

  3. Single-cell telomere-length quantification couples telomere length to meristem activity and stem cell development in Arabidopsis.

    PubMed

    González-García, Mary-Paz; Pavelescu, Irina; Canela, Andrés; Sevillano, Xavier; Leehy, Katherine A; Nelson, Andrew D L; Ibañes, Marta; Shippen, Dorothy E; Blasco, Maria A; Caño-Delgado, Ana I

    2015-05-12

    Telomeres are specialized nucleoprotein caps that protect chromosome ends assuring cell division. Single-cell telomere quantification in animals established a critical role for telomerase in stem cells, yet, in plants, telomere-length quantification has been reported only at the organ level. Here, a quantitative analysis of telomere length of single cells in Arabidopsis root apex uncovered a heterogeneous telomere-length distribution of different cell lineages showing the longest telomeres at the stem cells. The defects in meristem and stem cell renewal observed in tert mutants demonstrate that telomere lengthening by TERT sets a replicative limit in the root meristem. Conversely, the long telomeres of the columella cells and the premature stem cell differentiation plt1,2 mutants suggest that differentiation can prevent telomere erosion. Overall, our results indicate that telomere dynamics are coupled to meristem activity and continuous growth, disclosing a critical association between telomere length, stem cell function, and the extended lifespan of plants. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Excitation-neurogenesis coupling in adult neural stem/progenitor cells.

    PubMed

    Deisseroth, Karl; Singla, Sheela; Toda, Hiroki; Monje, Michelle; Palmer, Theo D; Malenka, Robert C

    2004-05-27

    A wide variety of in vivo manipulations influence neurogenesis in the adult hippocampus. It is not known, however, if adult neural stem/progenitor cells (NPCs) can intrinsically sense excitatory neural activity and thereby implement a direct coupling between excitation and neurogenesis. Moreover, the theoretical significance of activity-dependent neurogenesis in hippocampal-type memory processing networks has not been explored. Here we demonstrate that excitatory stimuli act directly on adult hippocampal NPCs to favor neuron production. The excitation is sensed via Ca(v)1.2/1.3 (L-type) Ca(2+) channels and NMDA receptors on the proliferating precursors. Excitation through this pathway acts to inhibit expression of the glial fate genes Hes1 and Id2 and increase expression of NeuroD, a positive regulator of neuronal differentiation. These activity-sensing properties of the adult NPCs, when applied as an "excitation-neurogenesis coupling rule" within a Hebbian neural network, predict significant advantages for both the temporary storage and the clearance of memories.

  5. 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.

  6. Stem cells--clinical application and perspectives.

    PubMed

    Brehm, Michael; Zeus, Tobias; Strauer, Bodo Eckehard

    2002-11-01

    Augmentation of myocardial performance in experimental models of therapeutic infarction and heart failure has been achieved by transplantation of exogenous cells into damaged myocardium. The quest for suitable donor cells has prompted research into the use of both embryonic stem cells and adult somatic stem cells. Recently, there has been a growing body of evidence that multipotent somatic stem cells in adult bone marrow exhibit tremendous functional plasticity and can reprogram in a new environmental tissue niche to give rise to cell lineages specific for new organ site. This phenomenon has made huge impact on myocardial biology, while multipotent adult bone marrow hematopoeitic stem cells and mesechymal stem cells can repopulate infarcted rodent myocardium and differentiate into both cardiomyocytes and new blood vessels. These data, coupled with the identification of a putative primitive cardiac stem cell population in the adult human heart, may open the way for novel therapeutic modalities for enhancing myocardial performance and treating heart failure.

  7. 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.

  8. Cellular Mechanisms of Somatic Stem Cell Aging

    PubMed Central

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  9. Stem cells in retinal regeneration: past, present and future.

    PubMed

    Ramsden, Conor M; Powner, Michael B; Carr, Amanda-Jayne F; Smart, Matthew J K; da Cruz, Lyndon; Coffey, Peter J

    2013-06-01

    Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

  10. Deubiquitylating enzymes as cancer stem cell therapeutics.

    PubMed

    Haq, Saba; Suresh, Bharathi; Ramakrishna, Suresh

    2018-01-01

    The focus of basic and applied research on core stem cell transcription factors has paved the way to initial delineation of their characteristics, their regulatory mechanisms, and the applicability of their regulatory proteins for protein-induced pluripotent stem cells (protein-IPSC) generation and in further clinical settings. Striking parallels have been observed between cancer stem cells (CSCs) and stem cells. For the maintenance of stem cells and CSC pluripotency and differentiation, post translational modifications (i.e., ubiquitylation and deubiquitylation) are tightly regulated, as these modifications result in a variety of stem cell fates. The identification of deubiquitylating enzymes (DUBs) involved in the regulation of core stem cell transcription factors and CSC-related proteins might contribute to providing novel insights into the implications of DUB regulatory mechanisms for governing cellular reprogramming and carcinogenesis. Moreover, we propose the novel possibility of applying DUBs coupled with core transcription factors to improve protein-iPSC generation efficiency. Additionally, this review article further illustrates the potential of applying DUB inhibitors as a novel therapeutic intervention for targeting CSCs. Thus, defining DUBs as core pharmacological targets implies that future endeavors to develop their inhibitors may revolutionize our ability to regulate stem cell maintenance and differentiation, somatic cell reprogramming, and cancer stem cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Stem cells for cardiac repair: an introduction

    PubMed Central

    du Pré, Bastiaan C; Doevendans, Pieter A; van Laake, Linda W

    2013-01-01

    Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires administration of stem cell-derived cardiac cells at the right time using the right mode of delivery. Once delivered, transplanted cells need vascularization, electrophysiological coupling with the injured heart, and prevention of immunological rejection. Finally, stem cell therapy needs to be safe, reproducible, and affordable. In this review, we will give an introduction to the principles of stem cell based cardiac repair. PMID:23888179

  12. 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 ...

  13. 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.

  14. Recent Advances in Lgr5+ Stem Cell Research.

    PubMed

    Leung, Carly; Tan, Si Hui; Barker, Nick

    2018-05-01

    The discovery of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) as both a marker of adult stem cells and a critical modulator of their activity via its role as an effector of Wnt/R-spondin (Rspo) signaling has driven major advances in our understanding of stem cell biology during homeostasis, regeneration, and disease. Exciting new mouse and organoid culture models developed to study the endogenous behavior of Lgr5-expressing cells in health and disease settings have revealed the existence of facultative stem cell populations responsible for tissue regeneration, cancer stem cells (CSCs) driving metastasis in the gut, and Lgr5 + niche cells in the lung. Here we review these recent advances and discuss their impact on efforts to harness the therapeutic potential of adult stem cells and their cancer counterparts in the clinic. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Generation of male differentiated germ cells from various types of stem cells.

    PubMed

    Hou, Jingmei; Yang, Shi; Yang, Hao; Liu, Yang; Liu, Yun; Hai, Yanan; Chen, Zheng; Guo, Ying; Gong, Yuehua; Gao, Wei-Qiang; Li, Zheng; He, Zuping

    2014-06-01

    Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients. © 2014 Society for Reproduction and Fertility.

  17. Local calcium signalling is mediated by mechanosensitive ion channels in mesenchymal stem cells

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

    Chubinskiy-Nadezhdin, Vladislav I., E-mail: vchubinskiy@gmail.com; Vasileva, Valeria Y.; Pugovkina, Natalia A.

    Mechanical forces are implicated in key physiological processes in stem cells, including proliferation, differentiation and lineage switching. To date, there is an evident lack of understanding of how external mechanical cues are coupled with calcium signalling in stem cells. Mechanical reactions are of particular interest in adult mesenchymal stem cells because of their promising potential for use in tissue remodelling and clinical therapy. Here, single channel patch-clamp technique was employed to search for cation channels involved in mechanosensitivity in mesenchymal endometrial-derived stem cells (hMESCs). Functional expression of native mechanosensitive stretch-activated channels (SACs) and calcium-sensitive potassium channels of different conductances inmore » hMESCs was shown. Single current analysis of stretch-induced channel activity revealed functional coupling of SACs and BK channels in plasma membrane. The combination of cell-attached and inside-out experiments have indicated that highly localized Ca{sup 2+} entry via SACs triggers BK channel activity. At the same time, SK channels are not coupled with SACs despite of high calcium sensitivity as compared to BK. Our data demonstrate novel mechanism controlling BK channel activity in native cells. We conclude that SACs and BK channels are clusterized in functional mechanosensitive domains in the plasma membrane of hMESCs. Co-clustering of ion channels may significantly contribute to mechano-dependent calcium signalling in stem cells. - Highlights: • Stretch-induced channel activity in human mesenchymal stem cells was analyzed. • Functional expression of SACs and Ca{sup 2+}-sensitive BK and SK channels was shown. • Local Ca{sup 2+} influx via stretch-activated channels triggers BK channel activity. • SK channels are not coupled with SACs despite higher sensitivity to [Ca{sup 2+}]{sub i}. • Functional clustering of SACs and BK channels in stem cell membrane is proposed.« less

  18. Human embryonic stem cell lines: socio-legal concerns and therapeutic promise.

    PubMed

    McLaren, Anne

    2002-10-01

    Stem cell lines would be very valuable for the repair of diseased or damaged organs. Stem cells derived from adult tissues raise few ethical problems, and would not be rejected if derived from the patient. They show considerable plasticity and might be appropriate for some clinical conditions, but they tend not to grow well in culture. Stem cells derived from the early human embryo proliferate indefinitely in culture and can give rise to many different tissues, but their derivation requires destruction of the embryo, which is not ethically acceptable in some countries. Other countries allow strictly regulated destructive research on human embryos, usually those that have been produced for infertile couples in infertility clinics. Embryos that are no longer required for the couple's own reproductive project could be donated for research rather than just discarded. Different approaches are being developed to avoid immunological rejection of embryonic stem cells used for therapy. Derivation of embryonic stem cell lines by somatic cell nuclear transfer ('cloning') from the patients themselves might be one possible approach, but is unlikely to be used in routine clinical practice if more cost-effective methods are available.

  19. 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 ...

  20. 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.

  1. 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.

  2. 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 ...

  3. Curbing stem cell tourism in South Africa.

    PubMed

    Meissner-Roloff, Madelein; Pepper, Michael S

    2013-12-01

    Stem cells have received much attention globally due in part to the immense therapeutic potential they harbor. Unfortunately, malpractice and exploitation (financial and emotional) of vulnerable patients have also drawn attention to this field as a result of the detrimental consequences experienced by some individuals that have undergone unproven stem cell therapies. South Africa has had limited exposure to stem cells and their applications and, while any exploitation is detrimental to the field of stem cells, South Africa is particularly vulnerable in this regard. The current absence of adequate legislation and the inability to enforce existing legislation, coupled to the sea of misinformation available on the Internet could lead to an increase in illegitimate stem cell practices in South Africa. Circumstances are already precarious because of a lack of understanding of concepts involved in stem cell applications. What is more, credible and easily accessible information is not available to the public. This in turn cultivates fears born out of existing superstitions, cultural beliefs, rituals and practices. Certain cultural or religious concerns could potentially hinder the effective application of stem cell therapies in South Africa and novel ways of addressing these concerns are necessary. Understanding how scientific progress and its implementation will affect each individual and, consequently, the community, will be of cardinal importance to the success of the fields of stem cell therapy and regenerative medicine in South Africa. A failure to understand the ethical, cultural or moral ramifications when new scientific concepts are introduced could hinder the efficacy and speed of bringing discoveries to the patient. Neglecting proper procedure for establishing the field would lead to long delays in gaining public support in South Africa. Understanding the dangers of stem cell tourism - where vulnerable patients are subjected to unproven stem cell therapies that

  4. 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

  5. Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

    PubMed

    Barut Selver, Özlem; Yağcı, Ayşe; Eğrilmez, Sait; Gürdal, Mehmet; Palamar, Melis; Çavuşoğlu, Türker; Ateş, Utku; Veral, Ali; Güven, Çağrı; Wolosin, Jose Mario

    2017-10-01

    The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using

  6. 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 ...

  7. 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.

  8. 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.

  9. 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.

  10. Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling*

    PubMed Central

    Chanmee, Theerawut; Ontong, Pawared; Izumikawa, Tomomi; Higashide, Miho; Mochizuki, Nobutoshi; Chokchaitaweesuk, Chatchadawalai; Khansai, Manatsanan; Nakajima, Kazuki; Kakizaki, Ikuko; Kongtawelert, Prachya; Taniguchi, Naoyuki; Itano, Naoki

    2016-01-01

    Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. As in many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known about how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells. These integrated approaches disclosed an acceleration of metabolic flux in the hexosamine biosynthetic pathway (HBP). A metabolic shift toward glycolysis was also evident by quantitative targeted metabolomics, which was validated by the expression profiles of key glycolytic enzymes. Forced expression of glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1), an HBP rate-limiting enzyme, resembled the results of HA overproduction with regard to HIF-1α accumulation and glycolytic program, whereas GFAT1 inhibition significantly decreased HIF-1α protein level in HA-overproducing cancer cells. Moreover, inhibition of the HBP-HIF-1 axis abrogated HA-driven glycolytic enhancement and reduced the CSC-like subpopulation. Taken together, our results provide compelling evidence that HA production regulates the metabolic and CSC-like properties of breast cancer cells via HBP-coupled HIF-1 signaling. PMID:27758869

  11. 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…

  12. 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.

  13. The mechanical coupling of adult marrow stromal stem cells during cardiac regeneration assessed in a 2-D co-culture model

    PubMed Central

    Valarmathi, Mani T.; Fuseler, John W.; Goodwin, Richard L.; Davis, Jeffrey M.; Potts, Jay D.

    2011-01-01

    Postnatal cardiomyocytes undergo terminal differentiation and a restricted number of human cardiomyocytes retain the ability to divide and regenerate in response to ischemic injury. However, whether these neo-cardiomyocytes are derived from endogenous population of resident cardiac stem cells or from the exogenous double assurance population of resident bone marrow-derived stem cells that populate the damaged myocardium is unresolved and under intense investigation. The vital challenge is to ameliorate and/or regenerate the damaged myocardium. This can be achieved by stimulating proliferation of native quiescent cardiomyocytes and/or cardiac stem cell, or by recruiting exogenous autologous or allogeneic cells such as fetal or embryonic cardiomyocyte progenitors or bone marrow-derived stromal stem cells. The prerequisites are that these neo-cardiomyocytes must have the ability to integrate well within the native myocardium and must exhibit functional synchronization. Adult bone marrow stromal cells (BMSCs) have been shown to differentiate into cardiomyocyte-like cells both in vitro and in vivo. As a result, BMSCs may potentially play an essential role in cardiac repair and regeneration, but this concept requires further validation. In this report, we have provided compelling evidence that functioning cardiac tissue can be generated by the interaction of multipotent BMSCs with embryonic cardiac myocytes (ECMs) in two-dimensional (2-D) co-cultures. The differentiating BMSCs were induced to undergo cardiomyogenic differentiation pathway and were able to express unequivocal electromechanical coupling and functional synchronization with ECMs. Our 2-D co-culture system provides a useful in vitro model to elucidate various molecular mechanisms underpinning the integration and orderly maturation and differentiation of BMSCs into neo-cardiomyocytes during myocardial repair and regeneration. PMID:21288568

  14. 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.

  15. Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.

    PubMed

    Kiratipaiboon, Chayanin; Tengamnuay, Parkpoom; Chanvorachote, Pithi

    2015-12-15

    Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated. This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells. The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry. The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles. These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. 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.

  17. In silico lineage tracing through single cell transcriptomics identifies a neural stem cell population in planarians.

    PubMed

    Molinaro, Alyssa M; Pearson, Bret J

    2016-04-27

    The planarian Schmidtea mediterranea is a master regenerator with a large adult stem cell compartment. The lack of transgenic labeling techniques in this animal has hindered the study of lineage progression and has made understanding the mechanisms of tissue regeneration a challenge. However, recent advances in single-cell transcriptomics and analysis methods allow for the discovery of novel cell lineages as differentiation progresses from stem cell to terminally differentiated cell. Here we apply pseudotime analysis and single-cell transcriptomics to identify adult stem cells belonging to specific cellular lineages and identify novel candidate genes for future in vivo lineage studies. We purify 168 single stem and progeny cells from the planarian head, which were subjected to single-cell RNA sequencing (scRNAseq). Pseudotime analysis with Waterfall and gene set enrichment analysis predicts a molecularly distinct neoblast sub-population with neural character (νNeoblasts) as well as a novel alternative lineage. Using the predicted νNeoblast markers, we demonstrate that a novel proliferative stem cell population exists adjacent to the brain. scRNAseq coupled with in silico lineage analysis offers a new approach for studying lineage progression in planarians. The lineages identified here are extracted from a highly heterogeneous dataset with minimal prior knowledge of planarian lineages, demonstrating that lineage purification by transgenic labeling is not a prerequisite for this approach. The identification of the νNeoblast lineage demonstrates the usefulness of the planarian system for computationally predicting cellular lineages in an adult context coupled with in vivo verification.

  18. 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.

  19. Concise Review: Conceptualizing Paralogous Stem-Cell Niches and Unfolding Bone Marrow Progenitor Cell Identities.

    PubMed

    Chen, Kevin G; Johnson, Kory R; McKay, Ronald D G; Robey, Pamela G

    2018-01-01

    Lineage commitment and differentiation of skeletal stem cells/bone marrow stromal cells (SSCs/BMSCs, often called bone marrow-derived "mesenchymal stem/stromal" cells) offer an important opportunity to study skeletal and hematopoietic diseases, and for tissue engineering and regenerative medicine. Currently, many studies in this field have relied on cell lineage tracing methods in mouse models, which have provided a significant advancement in our knowledge of skeletal and hematopoietic stem-cell niches in bone marrow (BM). However, there is a lack of agreement in numerous fundamental areas, including origins of various BM stem-cell niches, cell identities, and their physiological roles in the BM. In order to resolve these issues, we propose a new hypothesis of "paralogous" stem-cell niches (PSNs); that is, progressively altered parallel niches within an individual species throughout the life span of the organism. A putative PSN code seems to be plausible based on analysis of transcriptional signatures in two representative genes that encode Nes-GFP and leptin receptors, which are frequently used to monitor SSC lineage development in BM. Furthermore, we suggest a dynamic paralogous BM niche (PBMN) model that elucidates the coupling and uncoupling mechanisms between BM stem-cell niches and their zones of active regeneration during different developmental stages. Elucidation of these PBMNs would enable us to resolve the existing controversies, thus paving the way to achieving precision regenerative medicine and pharmaceutical applications based on these BM cell resources. Stem Cells 2018;36:11-21. © 2017 AlphaMed Press.

  20. The molecular signature of muscle stem cells is driven by nutrient availability and innate cell metabolism.

    PubMed

    Ryall, James G; Lynch, Gordon S

    2018-07-01

    To discuss how innate muscle stem-cell metabolism and nutrient availability can provide temporal regulation of chromatin accessibility and transcription. Fluorescence-activated cell sorting coupled with whole transcriptome sequencing revealed for the first time that quiescent and proliferating skeletal muscle stem cells exhibit a process of metabolic reprogramming, from fatty-acid oxidation during quiescence to glycolysis during proliferation. Using a combination of immunofluorescence and chromatin immunoprecipitation sequencing, this shift in metabolism has been linked to altered availability of key metabolites essential for histone (de)acetylation and (de)methylation, including acetyl-CoA, s-adenosylmethionine and α-ketoglutarate. Importantly, these changes in metabolite availability have been linked to muscle stem-cell function. Together, these results provide greater insight into how muscle stem cells interact with their local environment, with important implications for metabolic diseases, skeletal muscle regeneration and cell-transplantation therapies.

  1. 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.

  2. LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells via the IQGAP1-Rac1 pathway.

    PubMed

    Carmon, Kendra S; Gong, Xing; Yi, Jing; Wu, Ling; Thomas, Anthony; Moore, Catherine M; Masuho, Ikuo; Timson, David J; Martemyanov, Kirill A; Liu, Qingyun J

    2017-09-08

    Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts, and is highly up-regulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro ; however, deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear. Here, we show that LGR5 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1), an effector of Rac1/CDC42 GTPases, in the regulation of actin cytoskeleton dynamics and cell-cell adhesion. Specifically, LGR5 decreased levels of IQGAP1 phosphorylation at Ser-1441/1443, leading to increased binding of Rac1 to IQGAP1 and thus higher levels of cortical F-actin and enhanced cell-cell adhesion. LGR5 ablation in colon cancer cells and crypt stem cells resulted in loss of cortical F-actin, reduced cell-cell adhesion, and disrupted localization of adhesion-associated proteins. No evidence of LGR5 coupling to any of the four major subtypes of heterotrimeric G proteins was found. These findings suggest that LGR5 primarily functions via the IQGAP1-Rac1 pathway to strengthen cell-cell adhesion in normal adult crypt stem cells and colon cancer cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. The promises of stem cells: stem cell therapy for movement disorders.

    PubMed

    Mochizuki, Hideki; Choong, Chi-Jing; Yasuda, Toru

    2014-01-01

    Despite the multitude of intensive research, the exact pathophysiological mechanisms underlying movement disorders including Parkinson's disease, multiple system atrophy and Huntington's disease remain more or less elusive. Treatments to halt these disease progressions are currently unavailable. With the recent induced pluripotent stem cells breakthrough and accomplishment, stem cell research, as the vast majority of scientists agree, holds great promise for relieving and treating debilitating movement disorders. As stem cells are the precursors of all cells in the human body, an understanding of the molecular mechanisms that govern how they develop and work would provide us many fundamental insights into human biology of health and disease. Moreover, stem-cell-derived neurons may be a renewable source of replacement cells for damaged neurons in movement disorders. While stem cells show potential for regenerative medicine, their use as tools for research and drug testing is thought to have more immediate impact. The use of stem-cell-based drug screening technology could be a big boost in drug discovery for these movement disorders. Particular attention should also be given to the involvement of neural stem cells in adult neurogenesis so as to encourage its development as a therapeutic option. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Haemopoietic stem cells.

    PubMed

    Bellantuono, Ilaria

    2004-04-01

    Considerable effort has been made in recent years in understanding the mechanisms that govern stem cell generation, proliferation, self-renewal, commitment and lately plasticity. In the development of the haemopoietic system during embryonic and fetal life the notion of different pools of stem cells arising from the endothelium is gaining consensus. Gene expression profiling of populations of stem cells is bringing to light categories of genes important for self-renewal or commitment. Besides the role of transcription factors in lineage decision, the role of soluble factors and transmembrane proteins, very active at the time of embryo development, are taking central stage in the maintenance and in vitro expansion of haemopoietic stem cells (HSCs). The hierarchical model of haemopoietic development is being questioned with reports of lineage switching and plasticity of haemopoietic stem cells to non-haemopoietic cells. Yet the understanding of the overall process is still very fragmented and hypothetical. This is mainly due to the absence of appropriate markers to enable selection of homogeneous stem cell populations and the need to rely on retrospective functional assays, able only to determine the overall behaviour of a population of cells. This review is intended to be an overview of the haemopoietic system and a critical re-visitation of issues such as plasticity and self-renewal important for therapeutic applications of haemopoietic stem cells.

  6. 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.

  7. Coupling of solute transport and cell expansion in pea stems

    NASA Technical Reports Server (NTRS)

    Schmalstig, J. G.; Cosgrove, D. J.

    1990-01-01

    As cells expand and are displaced through the elongation zone of the epicotyl of etiolated pea (Pisum sativum L. var Alaska) seedlings, there is little net dilution of the cell sap, implying a coordination between cell expansion and solute uptake from the phloem. Using [14C] sucrose as a phloem tracer (applied to the hypogeous cotyledons), the pattern of label accumulation along the stem closely matched the growth rate pattern: high accumulation in the growing zone, little accumulation in nongrowing regions. Several results suggest that a major portion of phloem contents enters elongating cells through the symplast. We propose that the coordination between phloem transport and cell expansion is accomplished via regulatory pathways affecting both plasmodesmata conductivity and cell expansion.

  8. 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.

  9. 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.

  10. The potential for stem cells in cerebral palsy--piecing together the puzzle.

    PubMed

    Faulkner, Stuart D; Ruff, Crystal A; Fehlings, Michael G

    2013-06-01

    The substantial socioeconomic burden of a diagnosis of cerebral palsy, coupled with a positive anecdotal and media spin on stem cell treatments, drives many affected families to seek information and treatment outside of the current clinical and scientific realm. Preclinical studies using several types of stem and adult cells--including mesenchymal stem cells, neural precursor cells, olfactory ensheathing glia and Schwann cells--have demonstrated some regenerative and functional efficacy in neurologic paradigms. This paper describes the most common cell types investigated for transplant in vivo and summarizes the current state of early-phase clinical trials. It investigates the most relevant and promising coadministered therapies, including rehabilitation, drug targeting, magnetic stimulation, and bioengineering approaches. We highlight the need for adjunctive combinatorial strategies to successfully transfer stem cell treatments from bench to bedside. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. 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

  12. 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.

  13. Pluripotent stem cells.

    PubMed

    Verfaillie, C

    2009-05-01

    The isolation of human embryonic stem cells (ESC) in 1998 has created the hope that stem cells will one day be used to regenerate tissues and organs, even though it is obvious that a number of hurdles will need to be overcome for such therapies to become reality. The cloning of "Dolly" in 1997, more than 40 years after the first frogs were cloned, combined with the very fast progress made in our understanding of the molecular processes that govern the pluripotency of ESC has lead to the ability of scientists to recreate a pluripotent state in fibroblasts and other cells from mouse, rat and man, named induced pluripotent stem cells (iPSC). This feat makes it theoretically possible to create patient specific pluripotent stem cells whose differentiated progeny could be used in an autologous manner obviating the need for immunosuppression that would be needed to use allogeneic ESC-derived differentiated cells. In addition, the ability to generate custom made pluripotent stem cells will no doubt lead to the development of protein or small molecule drugs that can induce differentiation not only of iPSC or ESC to mature tissue cells, but also endogenous tissue stem cells. Moreover, it allows scientists to create models of human diseases and may aid the pharmaceutical industry in testing more rigorously toxicity of drugs for human differentiated cells. Thus, there is little doubt that progress in stem cell biology will change many aspects of medicine as we know it in the next one to two decades.

  14. Induced pluripotent stem (iPS) cells from human fetal stem cells.

    PubMed

    Guillot, Pascale V

    2016-02-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 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.

  16. [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.

  17. 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.

  18. Fish Stem Cell Cultures

    PubMed Central

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-01-01

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on “Fish Stem Cells and Nuclear Transfer”, we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer. PMID:21547056

  19. Fish stem cell cultures.

    PubMed

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-04-13

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on "Fish Stem Cells and Nuclear Transfer", we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  20. Sex, stem cells and tumors in the Drosophila ovary.

    PubMed

    Salz, Helen K

    2013-01-01

    The Drosophila Sex-lethal (Sxl) gene encodes a female-specific RNA binding protein that in somatic cells globally regulates all aspects of female-specific development and behavior. Sxl also has a critical, but less well understood, role in female germ cells. Germ cells without Sxl protein can adopt a stem cell fate when housed in a normal ovary, but fail to successfully execute the self-renewal differentiation fate switch. The failure to differentiate is accompanied by the inappropriate expression of a set of male specific markers, continued proliferation, and formation of a tumor. The findings in Chau et al., (2012) identify the germline stem cell maintenance factor nanos as one of its target genes, and suggest that Sxl enables the switch from germline stem cell to committed daughter cell by posttranscriptional downregulation of nanos expression. These studies provide the basis for a new model in which Sxl directly couples sexual identity with the self-renewal differentiation decision and raises several interesting questions about the genesis of the tumor phenotype.

  1. 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.

  2. Brain mesenchymal stem cells: The other stem cells of the brain?

    PubMed

    Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

    2014-04-26

    Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

  3. Autophagy in stem cells

    PubMed Central

    Guan, Jun-Lin; Simon, Anna Katharina; Prescott, Mark; Menendez, Javier A.; Liu, Fei; Wang, Fen; Wang, Chenran; Wolvetang, Ernst; Vazquez-Martin, Alejandro; Zhang, Jue

    2013-01-01

    Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future. PMID:23486312

  4. Engineering nanoscale stem cell niche: direct stem cell behavior at cell-matrix interface.

    PubMed

    Zhang, Yan; Gordon, Andrew; Qian, Weiyi; Chen, Weiqiang

    2015-09-16

    Biophysical cues on the extracellular matrix (ECM) have proven to be significant regulators of stem cell behavior and evolution. Understanding the interplay of these cells and their extracellular microenvironment is critical to future tissue engineering and regenerative medicine, both of which require a means of controlled differentiation. Research suggests that nanotopography, which mimics the local, nanoscale, topographic cues within the stem cell niche, could be a way to achieve large-scale proliferation and control of stem cells in vitro. This Progress Report reviews the history and contemporary advancements of this technology, and pays special attention to nanotopographic fabrication methods and the effect of different nanoscale patterns on stem cell response. Finally, it outlines potential intracellular mechanisms behind this response. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite

    PubMed Central

    Clingman, Carina C; Deveau, Laura M; Hay, Samantha A; Genga, Ryan M; Shandilya, Shivender MD; Massi, Francesca; Ryder, Sean P

    2014-01-01

    Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18–22 carbon ω-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi proteins are critical for development of the brain, blood, and epithelium. We identify stearoyl-CoA desaturase-1 as a MSI1 target, revealing a feedback loop between ω-9 fatty acid biosynthesis and MSI1 activity. We propose that other RRM proteins could act as metabolite sensors to couple gene expression changes to physiological state. DOI: http://dx.doi.org/10.7554/eLife.02848.001 PMID:24935936

  6. Concise Review: Plasma and Nuclear Membranes Convey Mechanical Information to Regulate Mesenchymal Stem Cell Lineage.

    PubMed

    Uzer, Gunes; Fuchs, Robyn K; Rubin, Janet; Thompson, William R

    2016-06-01

    Numerous factors including chemical, hormonal, spatial, and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well-characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on "outside-in" signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell uses integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these outside-in connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the biochemical signals generated at the cell membrane and the nucleus, and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis. Stem Cells 2016;34:1455-1463. © 2016 AlphaMed Press.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Fusion-independent expression of functional ACh receptors in mouse mesoangioblast stem cells contacting muscle cells

    PubMed Central

    Grassi, Francesca; Pagani, Francesca; Spinelli, Gabriele; Angelis, Luciana De; Cossu, Giulio; Eusebi, Fabrizio

    2004-01-01

    Mesoangioblasts are vessel-associated fetal stem cells that can be induced to differentiate into skeletal muscle, both in vitro and in vivo. Whether this is due to fusion or to transdifferentiation into bona fide satellite cells is still an open question, for mesoangioblasts as well as for other types of stem cells. The early steps of satellite cell myogenic differentiation involve MyoD activation, membrane hyperpolarization and the appearance of ACh sensitivity and gap junctional communication. If mesoangioblasts differentiate into satellite cells, these characteristics should be observed in stem cells prior to fusion into multinucleated myotubes. We have investigated the functional properties acquired by mononucleated green fluorescent protein (GFP)-positive mesoangioblasts co-cultured with differentiating C2C12 myogenic cells, using the patch-clamp technique. Mesoangioblasts whose membrane contacted myogenic cells developed a hyperpolarized membrane resting potential and ACh-evoked current responses. Dye and electrical coupling was observed among mesoangioblasts but not between mesoangioblasts and myotubes. Mouse MyoD was detected by RT-PCR both in single, mononucleated mesoangioblasts co-cultured with C2C12 myotubes and in the total mRNA from mouse mesoangioblasts co-cultured with human myotubes, but not in human myotubes or stem cells cultured in isolation. In conclusion, when co-cultured with muscle cells, mesoangioblasts acquire many of the functional characteristics of differentiating satellite cells in the absence of cell fusion, strongly indicating that these stem cells undergo transdifferentiation into satellite cells, when exposed to a myogenic environment. PMID:15319417

  13. 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

  14. Are stem cells drugs? The regulation of stem cell research and development.

    PubMed

    Rosen, Michael R

    2006-10-31

    Stem cell research and its clinical application have become political, social, and medical lightning rods, polarizing opinion among members of the lay community and among medical/scientific professionals. A potpourri of opinion, near-anecdotal observation, and scientifically sound data has sown confusion in ways rarely seen in the medical arts and sciences. A major issue is regulation, with different aspects of stem cell research falling within the purview of different government agencies and local offices. An overarching clearinghouse to review the field and recommend policy is lacking. In the following pages, I touch on the societal framework for regulation, the known and potential risks and benefits of cardiovascular stem cell therapies, whether stem cells should be regulated as drugs or in analogy to drugs, and if there is to be regulation, then by whom. In so doing, I refer to the stem cell literature only as it relates to the discussion of regulation because this is not a review of stem cell research; it is an opinion regarding regulation.

  15. Brain mesenchymal stem cells: The other stem cells of the brain?

    PubMed Central

    Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

    2014-01-01

    Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression. PMID:24772240

  16. Mesenchymal stem cells and their conditioned medium improve integration of purified induced pluripotent stem cell-derived cardiomyocyte clusters into myocardial tissue.

    PubMed

    Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E A; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad; Khalil, Markus

    2014-03-15

    Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium.

  17. Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

    PubMed

    Celià-Terrassa, Toni

    2018-05-04

    Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

  18. High-content screening of small compounds on human embryonic stem cells.

    PubMed

    Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

    2010-08-01

    Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

  19. The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells.

    PubMed

    Park, Hyo-Jung; Kim, Jun-Kyum; Jeon, Hye-Min; Oh, Se-Yeong; Kim, Sung-Hak; Nam, Do-Hyun; Kim, Hyunggee

    2010-11-01

    A growing body of evidence indicates that deregulation of stem cell fate determinants is a hallmark of many types of malignancies. The neural stem cell fate determinant TLX plays a pivotal role in neurogenesis in the adult brain by maintaining neural stem cells. Here, we report a tumorigenic role of TLX in brain tumor initiation and progression. Increased TLX expression was observed in a number of glioma cells and glioma stem cells, and correlated with poor survival of patients with gliomas. Ectopic expression of TLX in the U87MG glioma cell line and Ink4a/Arf-deficient mouse astrocytes (Ink4a/Arf(-/-) astrocytes) induced cell proliferation with a concomitant increase in cyclin D expression, and accelerated foci formation in soft agar and tumor formation in in vivo transplantation assays. Furthermore, overexpression of TLX in Ink4a/Arf(-/-) astrocytes inhibited cell migration and invasion and promoted neurosphere formation and Nestin expression, which are hallmark characteristics of glioma stem cells, under stem cell culture conditions. Our results indicate that TLX is involved in glioma stem cell genesis and represents a potential therapeutic target for this type of malignancy.

  20. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development.

    PubMed

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

    2012-12-10

    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies.

  1. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

    PubMed Central

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A

    2012-01-01

    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies. PMID:24710551

  2. 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."

  3. 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

  4. 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.

  5. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid.

    PubMed

    Aihara, Eitaro; Mahe, Maxime M; Schumacher, Michael A; Matthis, Andrea L; Feng, Rui; Ren, Wenwen; Noah, Taeko K; Matsu-ura, Toru; Moore, Sean R; Hong, Christian I; Zavros, Yana; Herness, Scott; Shroyer, Noah F; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A; Montrose, Marshall H

    2015-11-24

    Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.

  6. Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

    PubMed Central

    Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A.; Montrose, Marshall H.

    2015-01-01

    Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration. PMID:26597788

  7. 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.

  8. 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

  9. 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.

  10. When stem cells grow old: phenotypes and mechanisms of stem cell aging

    PubMed Central

    Schultz, Michael B.; Sinclair, David A.

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

  11. 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.

  12. 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 ...

  13. Adipose-derived stem cell: a better stem cell than BMSC.

    PubMed

    Zhu, Yanxia; Liu, Tianqing; Song, Kedong; Fan, Xiubo; Ma, Xuehu; Cui, Zhanfeng

    2008-08-01

    To further study the proliferation and multi-differentiation potentials of adipose-derived stem cells (ADSCs), the cells were isolated with improved methods and their growth curves were achieved with cck-8. Surface protein expression was analyzed by flow cytometry to characterize the cell phenotype. The multi-lineage potential of ADSCs was testified by differentiating cells with adipogenic, chondrogenic, osteogenic, and myogenic inducers. The results showed that about 5 x 10(5) stem cells could be obtained from 400 to 600 mg adipose tissue. The ADSCs can be continuously cultured in vitro for up to 1 month without passage and they have several logarithmic growth phases during the culture period. Also, the flow cytometry analysis showed that ADSCs expressed high levels of stem cell-related antigens (CD13, CD29, CD44, CD105, and CD166), while did not express hematopoiesis-related antigens CD34 and CD45, and human leukocyte antigen HLA-DR was also negative. Moreover, stem cell-related transcription factors, Nanog, Oct-4, Sox-2, and Rex-1 were positively expressed in ADSCs. The expression of alkaline phosphatase (ALP) was detected in the early osteogenic induction and the calcified nodules were observed by von Kossa staining. Intracellular lipid droplets could be observed by Oil Red staining. Differentiated cardiomyocytes were observed by connexin43 fluorescent staining. In order to obtain more stem cells, we can subculture ADSCs every 14 days instead of the normal 5 days. ADSCs still keep strong proliferation ability, maintain their phenotypes, and have stronger multi-differentiation potential after 25 passages. Copyright 2008 John Wiley & Sons, Ltd.

  14. Stem Cells and Aging.

    PubMed

    Koliakos, George

    2017-02-01

    The article is a presentation at the 4th Conference of ESAAM, which took place on October 30-31, 2015, in Athens, Greece. Its purpose was not to cover all aspects of cellular aging but to share with the audience of the Conference, in a 15-minute presentation, current knowledge about the rejuvenating and repairing somatic stem cells that are distinct from other stem cell types (such as embryonic or induced pluripotent stem cells), emphasize that our body in old age cannot take advantage of these rejuvenating cells, and provide some examples of novel experimental stem cell applications in the field of rejuvenation and antiaging biomedical research.

  15. 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.

  16. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  17. Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy.

    PubMed

    Pramanik, Subrata; Sulistio, Yanuar Alan; Heese, Klaus

    2017-11-01

    Neurotrophins (NTs) are members of a neuronal growth factor protein family whose action is mediated by the tropomyosin receptor kinase (TRK) receptor family receptors and the p75 NT receptor (p75NTR), a member of the tumor necrosis factor (TNF) receptor family. Although NTs were first discovered in neurons, recent studies have suggested that NTs and their receptors are expressed in various types of stem cells mediating pivotal signaling events in stem cell biology. The concept of stem cell therapy has already attracted much attention as a potential strategy for the treatment of neurodegenerative diseases (NDs). Strikingly, NTs, proNTs, and their receptors are gaining interest as key regulators of stem cells differentiation, survival, self-renewal, plasticity, and migration. In this review, we elaborate the recent progress in understanding of NTs and their action on various stem cells. First, we provide current knowledge of NTs, proNTs, and their receptor isoforms and signaling pathways. Subsequently, we describe recent advances in the understanding of NT activities in various stem cells and their role in NDs, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). Finally, we compile the implications of NTs and stem cells from a clinical perspective and discuss the challenges with regard to transplantation therapy for treatment of AD and PD.

  18. [Stem cells in adults].

    PubMed

    Borge, O J; Funderud, S

    2001-08-30

    We present a literature review of the plasticity observed by adult stem cells. We have reviewed the literature regarding stem cells from adults in order to summarise their ability to generate cells of other types than those of the tissue/organ from which they were isolated. Adult stem cells have recently been demonstrated to terminally differentiate into cells of other tissues than those from which they were originally isolated. For example, bone marrow cells have been shown to generate liver, nerve, heart and skeletal muscle cells in addition to their well-known ability to produce blood and mesenchymal cells. Most studies demonstrate a proof-of-principle in animal models; much more research is needed before adult stem cells can be utilised in human medicine. However, the published reports are encouraging and give reasons for a cautious optimism with regard to future clinical use.

  19. Quality Assurance in Stem Cell Banking: Emphasis on Embryonic and Induced Pluripotent Stem Cell Banking.

    PubMed

    Kallur, Therése; Blomberg, Pontus; Stenfelt, Sonya; Tryggvason, Kristian; Hovatta, Outi

    2017-01-01

    For quality assurance (QA) in stem cell banking, a planned system is needed to ensure that the banked products, stem cells, meet the standards required for research, clinical use, and commercial biotechnological applications. QA is process oriented, avoids, or minimizes unacceptable product defects, and particularly encompasses the management and operational systems of the bank, as well as the ethical and legal frameworks. Quality control (QC ) is product oriented and therefore ensures the stem cells of a bank are what they are expected to be. Testing is for controlling, not assuring, product quality, and is therefore a part of QC , not QA. Like QA, QC is essential for banking cells for quality research and translational application (Schwartz et al., Lancet 379:713-720, 2012). Human embryonic stem cells (hESCs), as cells derived from donated supernumerary embryos from in vitro fertilization (IVF) therapy, are different from other stem cell types in resulting from an embryo that has had two donors . This imposes important ethical and legal constraints on the utility of the cells, which, together with quite specific culture conditions, require special attention in the QA system. Importantly, although the origin and derivation of induced pluripotent stem cells (iPSCs ) differ from that of hESCs, many of the principles of QA for hESC banking are applicable to iPSC banking (Stacey et al., Cell Stem Cell 13:385-388, 2013). Furthermore, despite differences between the legal and regulatory frameworks for hESC and iPSC banking between different countries, the requirements for QA are being harmonized (Stacey et al., Cell Stem Cell 13:385-388, 2013; International Stem Cell Banking Initiative, Stem Cell Rev 5:301-314, 2009).

  20. Post-transcriptional modifications in development and stem cells.

    PubMed

    Frye, Michaela; Blanco, Sandra

    2016-11-01

    Cells adapt to their environment by linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. Among these, mechanisms that couple environmental cues to the regulation of protein translation are not well understood. Chemical modifications of RNA allow rapid cellular responses to external stimuli by modulating a wide range of fundamental biochemical properties and processes, including the stability, splicing and translation of messenger RNA. In this Review, we focus on the occurrence of N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C) and pseudouridine (Ψ) in RNA, and describe how these RNA modifications are implicated in regulating pluripotency, stem cell self-renewal and fate specification. Both post-transcriptional modifications and the enzymes that catalyse them modulate stem cell differentiation pathways and are essential for normal development. © 2016. Published by The Company of Biologists Ltd.

  1. Stem cell plasticity.

    PubMed

    Lakshmipathy, Uma; Verfaillie, Catherine

    2005-01-01

    The central dogma in stem cell biology has been that cells isolated from a particular tissue can renew and differentiate into lineages of the tissue it resides in. Several studies have challenged this idea by demonstrating that tissue specific cell have considerable plasticity and can cross-lineage restriction boundary and give rise to cell types of other lineages. However, the lack of a clear definition for plasticity has led to confusion with several reports failing to demonstrate that a single cell can indeed differentiate into multiple lineages at significant levels. Further, differences between results obtained in different labs has cast doubt on some results and several studies still await independent confirmation. In this review, we critically evaluate studies that report stem cell plasticity using three rigid criteria to define stem cell plasticity; differentiation of a single cell into multiple cell lineages, functionality of differentiated cells in vitro and in vivo, robust and persistent engraft of transplanted cells.

  2. When stem cells grow old: phenotypes and mechanisms of stem cell aging.

    PubMed

    Schultz, Michael B; Sinclair, David A

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. © 2016. Published by The Company of Biologists Ltd.

  3. The UK Stem Cell Bank: a UK government-funded, international resource center for stem cell research.

    PubMed

    Stacey, Glyn; Hunt, Charles J

    2006-01-01

    The UK Stem Cell Bank is a UK Research Council-funded initiative that aims to provide ethically sourced and quality controlled stocks of cells for researchers and also establish seed stocks of cell lines for clinical trials. Whilst the Bank is prohibited from carrying out basic stem cell research (to avoid conflicts of interest) it is working to improve stem cell banking procedures including cryopreservation, characterization and quality control. The Bank also supports training activities and has provided the hub for the International Stem Cell Initiative, which includes 17 expert stem cell centers aiming to characterize a large number of human embryonic stem cell lines in a standardized way to improve our understanding of the characteristics of these cells.

  4. 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.

  5. Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments

    PubMed Central

    Goodell, Margaret A.; Nguyen, Hoang; Shroyer, Noah

    2017-01-01

    Somatic stem cells replenish many tissues throughout life to repair damage and to maintain tissue homeostasis. Stem cell function is frequently described as following a hierarchical model in which a single master cell undergoes self-renewal and differentiation into multiple cell types and is responsible for most regenerative activity. However, recent data from studies on blood, skin and intestinal epithelium all point to the concomitant action of multiple types of stem cells with distinct everyday roles. Under stress conditions such as acute injury, the surprising developmental flexibility of these stem cells enables them to adapt to diverse roles and to acquire different regeneration capabilities. This paradigm shift raises many new questions about the developmental origins, inter-relationships and molecular regulation of these multiple stem cell types. PMID:25907613

  6. 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.

  7. What's missing? Discussing stem cell translational research in educational information on stem cell "tourism".

    PubMed

    Master, Zubin; Zarzeczny, Amy; Rachul, Christen; Caulfield, Timothy

    2013-01-01

    Stem cell tourism is a growing industry in which patients pursue unproven stem cell therapies for a wide variety of illnesses and conditions. It is a challenging market to regulate due to a number of factors including its international, online, direct-to-consumer approach. Calls to provide education and information to patients, their families, physicians, and the general public about the risks associated with stem cell tourism are mounting. Initial studies examining the perceptions of patients who have pursued stem cell tourism indicate many are highly critical of the research and regulatory systems in their home countries and believe them to be stagnant and unresponsive to patient needs. We suggest that educational material should include an explanation of the translational research process, in addition to other aspects of stem cell tourism, as one means to help promote greater understanding and, ideally, curb patient demand for unproven stem cell interventions. The material provided must stress that strong scientific research is required in order for therapies to be safe and have a greater chance at being effective. Through an analysis of educational material on stem cell tourism and translational stem cell research from patient groups and scientific societies, we describe essential elements that should be conveyed in educational material provided to patients. Although we support the broad dissemination of educational material on stem cell translational research, we also acknowledge that education may simply not be enough to engender patient and public trust in domestic research and regulatory systems. However, promoting patient autonomy by providing good quality information to patients so they can make better informed decisions is valuable in itself, irrespective of whether it serves as an effective deterrent of stem cell tourism. © 2013 American Society of Law, Medicine & Ethics, Inc.

  8. The Hippo signaling pathway in stem cell biology and cancer

    PubMed Central

    Mo, Jung-Soon; Park, Hyun Woo; Guan, Kun-Liang

    2014-01-01

    The Hippo signaling pathway, consisting of a highly conserved kinase cascade (MST and Lats) and downstream transcription coactivators (YAP and TAZ), plays a key role in tissue homeostasis and organ size control by regulating tissue-specific stem cells. Moreover, this pathway plays a prominent role in tissue repair and regeneration. Dysregulation of the Hippo pathway is associated with cancer development. Recent studies have revealed a complex network of upstream inputs, including cell density, mechanical sensation, and G-protein-coupled receptor (GPCR) signaling, that modulate Hippo pathway activity. This review focuses on the role of the Hippo pathway in stem cell biology and its potential implications in tissue homeostasis and cancer. PMID:24825474

  9. Pluripotent Stem Cells as a Robust Source of Mesenchymal Stem Cells.

    PubMed

    Luzzani, Carlos D; Miriuka, Santiago G

    2017-02-01

    Mesenchymal stem cells (MSC) have been extensively studied over the past years for the treatment of different diseases. Most of the ongoing clinical trials currently involve the use of MSC derived from adult tissues. This source may have some limitations, particularly with therapies that may require extensive and repetitive cell dosage. However, nowadays, there is a staggering growth in literature on a new source of MSC. There is now increasing evidence about the mesenchymal differentiation from pluripotent stem cell (PSC). Here, we summarize the current knowledge of pluripotent-derived mesenchymal stem cells (PD-MSC). We present a historical perspective on the subject, and then discuss some critical questions that remain unanswered.

  10. Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

    PubMed

    Duelen, Robin; Sampaolesi, Maurilio

    2017-02-01

    Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation. Copyright © 2017. Published by Elsevier B.V.

  11. Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

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

    Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth ofmore » undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.« less

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Hepatic stem/progenitor cells and stem-cell transplantation for the treatment of liver disease.

    PubMed

    Kakinuma, Sei; Nakauchi, Hiromitsu; Watanabe, Mamoru

    2009-01-01

    Allogeneic liver transplantation is still the only effective treatment available to patients with liver failure. However, because there is a serious shortage of liver donors, an alternative therapeutic approach is needed. Transplantation of mature hepatocytes has been evaluated in clinical trials, but the long-term efficacy remains unclear and the paucity of donor cells limits this strategy. Stem-cell transplantation is a more promising alternative approach. Several studies have provided information about the mechanism underlying the proliferation and differentiation of hepatic stem/progenitor cells. Moreover, in experimental models of liver disease, transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells led to donor cell-mediated repopulation of the liver and improved survival rates. However, before stem-cell transplantation can be applied in the clinic to treat liver failure in humans, it will be necessary to overcome several difficulties associated with the technique.

  17. [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.

  18. Stem Cells as Drug Delivery Methods: Application of Stem Cell Secretome for Regeneration

    PubMed Central

    Tran, Christine; Damaser, Margot S.

    2014-01-01

    Mesenchymal stem cells (MSC) are a unique cell population defined by their ability to indefinitely self-renew, differentiate into multiple cell lineages, and form clonal cell populations. It was originally thought that this ability for broad plasticity defined the therapeutic potential of MSCs. However, an expanding body of recent literature has brought growing awareness to the remarkable array of bioactive molecules produced by stem cells. This protein milieu or “secretome” comprises a diverse host of cytokines, chemokines, angiogenic factors, and growth factors. The autocrine/paracrine role of these molecules is being increasingly recognized as key to the regulation of many physiological processes including directing endogenous and progenitor cells to sites of injury as well as mediating apoptosis, scarring, and tissue revascularization. In fact, the immunomodulatory and paracrine role of these molecules may predominantly account for the therapeutic effects of MSCs given that many in vitro and in vivo studies have demonstrated limited stem cell engraftment at the site of injury. While the study of such a vast protein array remains challenging, technological advances in the field of proteomics have greatly facilitated our ability to analyze and characterize the stem cell secretome. Thus, stem cells can be considered as tunable pharmacological storehouses useful for combinatorial drug manufacture and delivery. As a cell-free option for regenerative medicine therapies, stem cell secretome has shown great potential in a variety of clinical applications including the restoration of function in cardiovascular, neurodegenerative, oncologic, and genitourinary pathologies. PMID:25451858

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Bioprinting for stem cell research

    PubMed Central

    Tasoglu, Savas; Demirci, Utkan

    2012-01-01

    Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

  4. [Bioethical challenges of stem cell tourism].

    PubMed

    Ventura-Juncá, Patricio; Erices, Alejandro; Santos, Manuel J

    2013-08-01

    Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research.

  5. 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

  6. The Emerging Cell Biology of Thyroid Stem Cells

    PubMed Central

    Latif, Rauf; Minsky, Noga C.; Ma, Risheng

    2011-01-01

    Context: Stem cells are undifferentiated cells with the property of self-renewal and give rise to highly specialized cells under appropriate local conditions. The use of stem cells in regenerative medicine holds great promise for the treatment of many diseases, including those of the thyroid gland. Evidence Acquisition: This review focuses on the progress that has been made in thyroid stem cell research including an overview of cellular and molecular events (most of which were drawn from the period 1990–2011) and discusses the remaining problems encountered in their differentiation. Evidence Synthesis: Protocols for the in vitro differentiation of embryonic stem cells, based on normal developmental processes, have generated thyroid-like cells but without full thyrocyte function. However, agents have been identified, including activin A, insulin, and IGF-I, which are able to stimulate the generation of thyroid-like cells in vitro. In addition, thyroid stem/progenitor cells have been identified within the normal thyroid gland and within thyroid cancers. Conclusions: Advances in thyroid stem cell biology are providing not only insight into thyroid development but may offer therapeutic potential in thyroid cancer and future thyroid cell replacement therapy. PMID:21778219

  7. Stem cells in pharmaceutical biotechnology.

    PubMed

    Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

    2011-11-01

    Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All

  8. HPV-Induced Field Cancerisation: Transformation of Adult Tissue Stem Cell Into Cancer Stem Cell.

    PubMed

    Olivero, Carlotta; Lanfredini, Simone; Borgogna, Cinzia; Gariglio, Marisa; Patel, Girish K

    2018-01-01

    Field cancerisation was originally described as a basis for multiple head and neck squamous cell carcinoma (HNSCC) and is a pre-malignant phenomenon that is frequently attributable to oncogenic human papillomavirus (HPV) infection. Our work on β-HPV-induced cutaneous squamous cell carcinomas identified a novel Lrig1+ hair follicle junctional zone keratinocyte stem cell population as the basis for field cancerisation. Herein, we describe the ability for HPV to infect adult tissue stem cells in order to establish persistent infection and induce their proliferation and displacement resulting in field cancerisation. By review of the HPV literature, we reveal how this mechanism is conserved as the basis of field cancerisation across many tissues. New insights have identified the capacity for HPV early region genes to dysregulate adult tissue stem cell self-renewal pathways ensuring that the expanded population preserve its stem cell characteristics beyond the stem cell niche. HPV-infected cells acquire additional transforming mutations that can give rise to intraepithelial neoplasia (IEN), from environmental factors such as sunlight or tobacco induced mutations in skin and oral cavity, respectively. With establishment of IEN, HPV viral replication is sacrificed with loss of the episome, and the tissue is predisposed to multiple cancer stem cell-driven carcinomas.

  9. Hematopoietic stem cells: can old cells learn new tricks?

    PubMed

    Ho, Anthony D; Punzel, Michael

    2003-05-01

    Since the establishment of cell lines derived from human embryonic stem (ES) cells, it has been speculated that out of such "raw material," we could some day produce all sorts of replacement parts for the human body. Human pluripotent stem cells can be isolated from embryonic, fetal, or adult tissues. Enormous self-renewal capacity and developmental potential are the characteristics of ES cells. Somatic stem cells, especially those derived from hematopoietic tissues, have also been reported to exhibit developmental potential heretofore not considered possible. The initial evidences for the plasticity potential of somatic stem cells were so encouraging that the opponents of ES cell research used them as arguments for restricting ES cell research. In the past months, however, critical issues have been raised challenging the validity and the interpretation of the initial data. Whereas hematopoietic stem-cell therapy has been a clinical reality for almost 40 years, there is still a long way to go in basic research before novel therapy strategies with stem cells as replacement for other organ systems can be established. Given the present status, we should keep all options open for research in ES cells and adult stem cells to appreciate the complexity of their differentiation pathways and the relative merits of various types of stem cells for regenerative medicine.

  10. 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

  11. The Stem Cell Club: a model for unrelated stem cell donor recruitment.

    PubMed

    Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

    2017-12-01

    Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

  12. 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.

  13. Ocular stem cells: a status update!

    PubMed Central

    2014-01-01

    Stem cells are unspecialized cells that have been a major focus of the field of regenerative medicine, opening new frontiers and regarded as the future of medicine. The ophthalmology branch of the medical sciences was the first to directly benefit from stem cells for regenerative treatment. The success stories of regenerative medicine in ophthalmology can be attributed to its accessibility, ease of follow-up and the eye being an immune-privileged organ. Cell-based therapies using stem cells from the ciliary body, iris and sclera are still in animal experimental stages but show potential for replacing degenerated photoreceptors. Limbal, corneal and conjunctival stem cells are still limited for use only for surface reconstruction, although they might have potential beyond this. Iris pigment epithelial, ciliary body epithelial and choroidal epithelial stem cells in laboratory studies have shown some promise for retinal or neural tissue replacement. Trabecular meshwork, orbital and sclera stem cells have properties identical to cells of mesenchymal origin but their potential has yet to be experimentally determined and validated. Retinal and retinal pigment epithelium stem cells remain the most sought out stem cells for curing retinal degenerative disorders, although treatments using them have resulted in variable outcomes. The functional aspects of the therapeutic application of lenticular stem cells are not known and need further attention. Recently, embryonic stem cell-derived retinal pigment epithelium has been used for treating patients with Stargardts disease and age-related macular degeneration. Overall, the different stem cells residing in different components of the eye have shown some success in clinical and animal studies in the field of regenerative medicine. PMID:25158127

  14. Progress in myeloma stem cells

    PubMed Central

    Cruz, Richard Dela; Tricot, Guido; Zangari, Maurizio; Zhan, Fenghuang

    2011-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and affects about 4 in 100,000 Americans. Even though much progress has been made in MM therapy, MM remains an incurable disease for the vast majority of patients. The existence of MM stem cell is considered one of the major causes of MM drug-resistance, leading to relapse. This highlights the importance and urgency of developing approaches to target MM stem cells. However, very little is known about the molecular characteristics of the MM stem cells, which makes it difficult to target MM stem cells therapeutically. Evidence of the existence of a myeloma stem cell has been provided by Matsui et al. showing that the CD138- and CD20+ fraction, which is a minor population of the MM cells, has a greater clonogenic potential and has the phenotype of a memory B-cell (CD19+, CD27+). In this review, we report recent progress of cell surface markers in cancer stem cells, especially in myeloma and the molecular mechanisms related to drug resistance and myeloma disease progression. PMID:22432075

  15. [Embryonic stem cells and therapeutic cloning].

    PubMed

    Sunde, A; Eftedal, I

    2001-08-30

    Increased interest in the therapeutic use of human stem cells has emerged following significant progress in ongoing research. The cloning of a sheep, the isolation of human embryonic stem cells, and the discovery that adult stem cells may be reprogrammed taken together give substance to hopes that novel principles of treatment may be developed for a variety of serious conditions. Embryonic stem cells are derived from pre-embryos at the blastocyst stage and may give rise to all bodily tissues and cells. Animal models have demonstrated that embryonic stem cells when transplanted into adult hosts may differentiate and develop into cells and tissues applicable for treatment of a variety of conditions, including Parkinson's disease, multiple sclerosis, spinal injuries, cardiac stroke and cancer. Transplanted embryonic stem cells are exposed to immune reactions similar to those acting on organ transplants, hence immunosuppression of the recipient is generally required. It is, however, possible to obtain embryonic stem cells that are genetically identical to the patient's own cells by means of therapeutic cloning techniques. The nucleus from a somatic cell is transferred into an egg after removal of the egg's own genetic material. Under specific condition the egg will use genetic information from the somatic cell in organising the formation of a blastocyst which in turn generates embryonic stem cells. These cells have a genetic composition identical to that of the patient and are suitable for stem cell therapy.

  16. Suspension culture of pluripotent stem cells: effect of shear on stem cell fate.

    PubMed

    Keller, Kevin C; Rodrigues, Beatriz; zur Nieden, Nicole I

    2014-01-01

    Despite significant promise, the routine usage of suspension cell culture to manufacture stem cell-derived differentiated cells has progressed slowly. Suspension culture is an innovative way of either expanding or differentiating cells and sometimes both are combined into a single bioprocess. Its advantages over static 2D culturing include a homogeneous and controllable culture environment and producing a large quantity of cells in a fraction of time. This feature makes suspension cell culture ideal for use in stem cell research and eventually ideal in the large-scale production of differentiated cells for regenerative medicine. Because of their tremendous differentiation capacities and unlimited growth properties, pluripotent stem cells (PSCs) in particular are considered potential sources for future cell-replacement therapies. Currently, expansion of PSCs is accomplished in 2D, which only permits a limited amount of cell growth per culture flask before cells need to be passaged. However, before stem cells can be applied clinically, several aspects of their expansion, such as directed growth, but also differentiation, need to be better controlled. This review will summarize recent advantages in suspension culture of PSCs, while at the same time highlighting current challenges.

  17. [Stem cells--cloning, plasticity, bioethic].

    PubMed

    Pflegerl, Pamina; Keller, Thomas; Hantusch, Brigitte; Hoffmann, Thomas Sören; Kenner, Lukas

    2008-01-01

    Stem cells with certain characteristics have become promising tools for molecular medicine. They have the potential to self-regenerate and to differentiate into specific tissues. Besides their great potential, embryonic stem cells (ESC) run the risk of enhanced tumorigenesis. The use of human embryonic stem cells (hESC) is ethically problematic because their isolation involves the destruction of human embryos. Recently developed methods generate are able to pluripotent stem cells from fibroblasts. Alternatives for ESC are adult stem cells (ASC) derived from bone marrow, cord blood, amniotic fluid and other tissues. The following article is on the basis of testimony of Lukas Kenner for the German Bundestag about the use of ESC for research, therapy and drug development. Ethical aspects are taken into consideration.

  18. Germline Stem Cells

    PubMed Central

    Spradling, Allan; Fuller, Margaret T.; Braun, Robert E.; Yoshida, Shosei

    2011-01-01

    Sperm and egg production requires a robust stem cell system that balances self-renewal with differentiation. Self-renewal at the expense of differentiation can cause tumorigenesis, whereas differentiation at the expense of self-renewal can cause germ cell depletion and infertility. In most organisms, and sometimes in both sexes, germline stem cells (GSCs) often reside in a defined anatomical niche. Factors within the niche regulate a balance between GSC self-renewal and differentiation. Asymmetric division of the germline stem cell to form daughter cells with alternative fates is common. The exception to both these tendencies is the mammalian testis where there does not appear to be an obvious anatomical niche and where GSC homeostasis is likely accomplished by a stochastic balance of self-renewal and differentiation and not by regulated asymmetric cell division. Despite these apparent differences, GSCs in all organisms share many common mechanisms, although not necessarily molecules, to guarantee survival of the germline. PMID:21791699

  19. 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.

  20. EuroStemCell: A European infrastructure for communication and engagement with stem cell research.

    PubMed

    Barfoot, Jan; Doherty, Kate; Blackburn, C Clare

    2017-10-01

    EuroStemCell is a large and growing network of organizations and individuals focused on public engagement with stem cells and regenerative medicine - a fluid and contested domain, where scientific, political, ethical, legal and societal perspectives intersect. Rooted in the European stem cell research community, this project has developed collaborative and innovative approaches to information provision and direct and online engagement, that reflect and respond to the dynamic growth of the field itself. EuroStemCell started as the communication and outreach component of a research consortium and subsequently continued as a stand-alone engagement initiative. The involvement of established European stem cell scientists has grown year-on-year, facilitating their participation in public engagement by allowing them to make high-value contributions with broad reach. The project has now had sustained support by partners and funders for over twelve years, and thus provides a model for longevity in public engagement efforts. This paper considers the evolution of the EuroStemCell project in response to - and in dialogue with - its evolving environment. In it, we aim to reveal the mechanisms and approaches taken by EuroStemCell, such that others within the scientific community can explore these ideas and be further enabled in their own public engagement endeavours. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Pituitary stem cells drop their mask.

    PubMed

    Vankelecom, Hugo

    2012-01-01

    The pituitary gland represents the organism's endocrine hub, integrating central and peripheral inputs to generate the appropriate hormonal signals that govern key physiological processes. To meet the changing endocrine demands, the gland has to flexibly remodel its hormone-producing cell compartment. Mechanisms underlying pituitary cellular plasticity, as well as homeostatic turnover, are poorly understood. Similar to other tissues, resident stem cells may participate in the generation of newborn cells. Although in the past recurrently postulated to exist, pituitary stem cells remained obscure until the quest recently regained momentum, resulting in a surge of studies that designated very strong candidates for the stem/progenitor cell position. The cells identified express stem cell-associated markers and signaling factors, as well as transcriptional regulators that play essential roles during pituitary embryogenesis. They exhibit the stem cell properties of multilineage differentiation and prominent efflux capacity ("side population" phenotype), and display a topographical pattern reminiscent of niche-like configurations. Yet, the stem cell tenet of long-term self-renewal remains to be unequivocally demonstrated. Taken together, pituitary stem cells commence to drop their mask. While their "face gradually becomes visible, the "character" they play in the pituitary awaits further disclosure. The aim of this review is to highlight the recent progress in pituitary stem/progenitor cell identification by sketching the historical context, describing the new findings with inclusion of critical and cautionary reflections, proposing a tentative stem/progenitor cell model, and pointing out remaining gaps and challenges. The recent acceleration in pituitary stem cell research may announce an exciting era in this endocrine field.

  2. 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 ( ...

  3. Genetics of Gonadal Stem Cell Renewal

    PubMed Central

    Greenspan, Leah Joy; de Cuevas, Margaret

    2015-01-01

    Stem cells are necessary for the maintenance of many adult tissues. Signals within the stem cell microenvironment, or niche, regulate the self-renewal and differentiation capability of these cells. Misregulation of these signals through mutation or damage can lead to overgrowth or depletion of different stem cell pools. In this review, we focus on the Drosophila testis and ovary, both of which contain well-defined niches, as well as the mouse testis, which has become a more approachable stem cell system with recent technical advances. We discuss the signals that regulate gonadal stem cells in their niches, how these signals mediate self-renewal and differentiation under homeostatic conditions, and how stress, whether from mutations or damage, can cause changes in cell fate and drive stem cell competition. PMID:26355592

  4. 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

  5. Ultra-thin Polyethylene glycol Coatings for Stem Cell Culture

    NASA Astrophysics Data System (ADS)

    Schmitt, Samantha K.

    Human mesenchymal stem cells (hMSCs) are a widely accessible and a clinically relevant cell type that are having a transformative impact on regenerative medicine. However, current clinical expansion methods can lead to selective changes in hMSC phenotype resulting from relatively undefined cell culture surfaces. Chemically defined synthetic surfaces can aid in understanding stem cell behavior. In particular we have developed chemically defined ultra-thin coatings that are stable over timeframes relevant to differentiation of hMSCs (several weeks). The approach employs synthesis of a copolymer with distinct chemistry in solution before application to a substrate. This provides wide compositional flexibility and allows for characterization of the orthogonal crosslinking and peptide binding groups. Characterization is done in solution by proton NMR and after crosslinking by X-ray photoelectron spectroscopy (XPS). The solubility of the copolymer in ethanol and low temperature crosslinking, expands its applicability to plastic substrates, in addition to silicon, glass, and gold. Cell adhesive peptides, namely Arg-Gly-Asp (RGD) fragments, are coupled to coating via different chemistries resulting in the urethane, amide or the thioester polymer-peptide bonds. Development of azlactone-based chemistry allowed for coupling in water at low peptide concentrations and resulted in either an amide or thioester bonds, depending on reactants. Characterization of the peptide functionalized coating by XPS, infrared spectroscopy and cell culture assays, showed that the amide linkages can present peptides for multiple weeks, while shorter-term presentation of a few days is possible using the more labile thioester bond. Regardless, coatings promoted initial adhesion and spreading of hMSCs in a peptide density dependent manner. These coatings address the following challenges in chemically defined cell culture simultaneously: (i) substrate adaptability, (ii) scalability over large areas

  6. 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.

  7. Cell motion predicts human epidermal stemness

    PubMed Central

    Toki, Fujio; Tate, Sota; Imai, Matome; Matsushita, Natsuki; Shiraishi, Ken; Sayama, Koji; Toki, Hiroshi; Higashiyama, Shigeki

    2015-01-01

    Image-based identification of cultured stem cells and noninvasive evaluation of their proliferative capacity advance cell therapy and stem cell research. Here we demonstrate that human keratinocyte stem cells can be identified in situ by analyzing cell motion during their cultivation. Modeling experiments suggested that the clonal type of cultured human clonogenic keratinocytes can be efficiently determined by analysis of early cell movement. Image analysis experiments demonstrated that keratinocyte stem cells indeed display a unique rotational movement that can be identified as early as the two-cell stage colony. We also demonstrate that α6 integrin is required for both rotational and collective cell motion. Our experiments provide, for the first time, strong evidence that cell motion and epidermal stemness are linked. We conclude that early identification of human keratinocyte stem cells by image analysis of cell movement is a valid parameter for quality control of cultured keratinocytes for transplantation. PMID:25897083

  8. Diabetes and Stem Cell Function

    PubMed Central

    Fujimaki, Shin; Wakabayashi, Tamami; Takemasa, Tohru; Asashima, Makoto; Kuwabara, Tomoko

    2015-01-01

    Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer's disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment. PMID:26075247

  9. 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

  10. Nanomaterials for Engineering Stem Cell Responses.

    PubMed

    Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K

    2015-08-05

    Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. The Fountain of Stem Cell-Based Youth? Online Portrayals of Anti-Aging Stem Cell Technologies.

    PubMed

    Rachul, Christen M; Percec, Ivona; Caulfield, Timothy

    2015-08-01

    The hype surrounding stem cell science has created a market opportunity for the cosmetic industry. Cosmetic and anti-aging products and treatments that make claims regarding stem cell technology are increasingly popular, despite a lack of evidence for safety and efficacy of such products. This study explores how stem cell-based products and services are portrayed to the public through online sources, in order to gain insight into the key messages available to consumers. A content analysis of 100 web pages was conducted to examine the portrayals of stem cell-based cosmetic and anti-aging products and treatments. A qualitative discourse analysis of one web page further examined how language contributes to the portrayals of these products and treatments to public audiences. The majority of web pages portrayed stem cell-based products as ready for public use. Very few web pages substantiated claims with scientific evidence, and even fewer mentioned any risks or limitations associated with stem cell science. The discourse analysis revealed that the framing and use of metaphor obscures the certainty of the efficacy of and length of time for stem cell-based anti-aging technology to be publicly available. This study highlights the need to educate patients and the public on the current limits of stem cell applications in this context. In addition, generating scientific evidence for stem cell-based anti-aging and aesthetic applications is needed for optimizing benefits and minimizing adverse effects for the public. Having more evidence on efficacy and risks will help to protect patients who are eagerly seeking out these treatments. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  12. The happy destiny of frozen haematopoietic stem cells: from immature stem cells to mature applications.

    PubMed

    de Vries, E G E; Vellenga, E; Kluin-Nelemans, J C; Mulder, N H

    2004-09-01

    Forty years ago, van Putten described in the European Journal of Cancer (see this issue) quantitative studies on the optimal storage techniques of mouse and monkey bone marrow suspensions. Survival of the animals after irradiation following injection with stored bone marrow cell suspensions was the endpoint. He observed some species differences, but based on the data obtained considered a careful trial of the glycerol-polyvinylpyrrolide (PVP) combination for storage of marrow in man was indicated. In spite of this, dimethyl sulphoxide has become the 'standard' cryopreservant for human marrow stem cells. Over the last 40 years, there has been a tremendous increase in knowledge about haematopoietic stem cells and their use in the clinic. Haematopoietic stem cells are now known to travel between the bone marrow and peripheral blood and are the best-characterised adult stem cells. These cells are currently widely used for transplantations in the clinic and are obtained from a wide variety of sources. These include the bone marrow, peripheral blood, cord blood, autologous as well as allogeneic stem cells from related or unrelated donors. Increasingly, data has become available that adult haematopoietic stem cells can generate differentiated cells belonging to other cell types, a process called "developmental plasticity". Thus, they may contribute to non-haematopoietic tissue repair in multiple organ systems. This has created a whole new potential therapeutic armamentarium for the application of haematopoietic stem cells outside of the area of malignancies and haematopoietic disorders.

  13. 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.

  14. Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue

    PubMed Central

    Yee, Karen K.; Li, Yan; Redding, Kevin M.; Iwatsuki, Ken; Margolskee, Robert F.; Jiang, Peihua

    2013-01-01

    Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knock-in allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of circumvallate and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue. PMID:23377989

  15. Stem cells: science, policy, and ethics

    PubMed Central

    Fischbach, Gerald D.; Fischbach, Ruth L.

    2004-01-01

    Human embryonic stem cells offer the promise of a new regenerative medicine in which damaged adult cells can be replaced with new cells. Research is needed to determine the most viable stem cell lines and reliable ways to promote the differentiation of pluripotent stem cells into specific cell types (neurons, muscle cells, etc.). To create new cell lines, it is necessary to destroy preimplantation blastocysts. This has led to an intense debate that threatens to limit embryonic stem cell research. The profound ethical issues raised call for informed, dispassionate debate. PMID:15545983

  16. Potential feasibility of dental stem cells for regenerative therapies: stem cell transplantation and whole-tooth engineering.

    PubMed

    Nakahara, Taka

    2011-07-01

    Multipotent mesenchymal stem cells from bone marrow are expected to be a somatic stem cell source for the development of new cell-based therapy in regenerative medicine. However, dental clinicians are unlikely to carry out autologous cell/tissue collection from patients (i.e., marrow aspiration) as a routine procedure in their clinics; hence, the utilization of bone marrow stem cells seems impractical in the dental field. Dental tissues harvested from extracted human teeth are well known to contain highly proliferative and multipotent stem cell compartments and are considered to be an alternative autologous cell source in cell-based medicine. This article provides a short overview of the ongoing studies for the potential application of dental stem cells and suggests the utilization of 2 concepts in future regenerative medicine: (1) dental stem cell-based therapy for hepatic and other systemic diseases and (2) tooth replacement therapy using the bioengineered human whole tooth, called the "test-tube dental implant." Regenerative therapies will bring new insights and benefits to the fields of clinical medicine and dentistry.

  17. A natural stem cell therapy? How novel findings and biotechnology clarify the ethics of stem cell research

    PubMed Central

    Patel, P

    2006-01-01

    The natural replacement of damaged cells by stem cells occurs actively and often in adult tissues, especially rapidly dividing cells such as blood cells. An exciting case in Boston, however, posits a kind of natural stem cell therapy provided to a mother by her fetus—long after the fetus is born. Because there is a profound lack of medical intervention, this therapy seems natural enough and is unlikely to be morally suspect. Nevertheless, we feel morally uncertain when we consider giving this type of therapy to patients who would not naturally receive it. Much has been written about the ethics of stem cell research and therapy; this paper will focus on how recent advances in biotechnology and biological understandings of development narrow the debate. Here, the author briefly reviews current stem cell research practices, revisits the natural stem cell therapy case for moral evaluation, and ultimately demonstrates the importance of permissible stem cell research and therapy, even absent an agreement about the definition of when embryonic life begins. Although one promising technology, blighted ovum utilisation, uses fertilised but developmentally bankrupt eggs, it is argued that utilisation of unfertilised eggs to derive totipotent stem cells obviates the moral debate over when life begins. There are two existing technologies that fulfil this criterion: somatic cell nuclear transfer and parthenogenic stem cell derivation. Although these technologies are far from therapeutic, concerns over the morality of embryonic stem cell derivation should not hinder their advancement. PMID:16574879

  18. 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.

  19. De novo generation of HSCs from somatic and pluripotent stem cell sources

    PubMed Central

    Vo, Linda T.

    2015-01-01

    Generating human hematopoietic stem cells (HSCs) from autologous tissues, when coupled with genome editing technologies, is a promising approach for cellular transplantation therapy and for in vitro disease modeling, drug discovery, and toxicology studies. Human pluripotent stem cells (hPSCs) represent a potentially inexhaustible supply of autologous tissue; however, to date, directed differentiation from hPSCs has yielded hematopoietic cells that lack robust and sustained multilineage potential. Cellular reprogramming technologies represent an alternative platform for the de novo generation of HSCs via direct conversion from heterologous cell types. In this review, we discuss the latest advancements in HSC generation by directed differentiation from hPSCs or direct conversion from somatic cells, and highlight their applications in research and prospects for therapy. PMID:25762177

  20. Stem cells in cardiac repair.

    PubMed

    Henning, Robert J

    2011-01-01

    Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells

  1. 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.

  2. Engineering stem cells for future medicine.

    PubMed

    Ricotti, Leonardo; Menciassi, Arianna

    2013-03-01

    Despite their great potential in regenerative medicine applications, stem cells (especially pluripotent ones) currently show a limited clinical success, partly due to a lack of biological knowledge, but also due to a lack of specific and advanced technological instruments able to overcome the current boundaries of stem cell functional maturation and safe/effective therapeutic delivery. This paper aims at describing recent insights, current limitations, and future horizons related to therapeutic stem cells, by analyzing the potential of different bioengineering disciplines in bringing stem cells toward a safe clinical use. First, we clarify how and why stem cells should be properly engineered and which could be in a near future the challenges and the benefits connected with this process. Second, we identify different routes toward stem cell differentiation and functional maturation, relying on chemical, mechanical, topographical, and direct/indirect physical stimulation. Third, we highlight how multiscale modeling could strongly support and optimize stem cell engineering. Finally, we focus on future robotic tools that could provide an added value to the extent of translating basic biological knowledge into clinical applications, by developing ad hoc enabling technologies for stem cell delivery and control.

  3. Ovarian cancer stem cells.

    PubMed

    Zeimet, A G; Reimer, D; Sopper, S; Boesch, M; Martowicz, A; Roessler, J; Wiedemair, A M; Rumpold, H; Untergasser, G; Concin, N; Hofstetter, G; Muller-Holzner, E; Fiegl, H; Marth, C; Wolf, D; Pesta, M; Hatina, J

    2012-01-01

    Because of its semi-solid character in dissemination and growth, advanced ovarian cancer with its hundreds of peritoneal tumor nodules and plaques appears to be an excellent in vivo model for studying the cancer stem cell hypothesis. The most important obstacle, however, is to adequately define and isolate these tumor-initiating cells endowed with the properties of anoikis-resistance and unlimited self-renewal. Until now, no universal single marker or marker constellation has been found to faithfully isolate (ovarian) cancer stem cells. As these multipotent cells are known to possess highly elaborated efflux systems for cytotoxic agents, these pump systems have been exploited to outline putative stem cells as a side-population (SP) via dye exclusion analysis. Furthermore, the cells in question have been isolated via flow cytometry on the basis of cell surface markers thought to be characteristic for stem cells.In the Vienna variant of the ovarian cancer cell line A2780 a proof-of-principle model with both a stable SP and a stable ALDH1A1+ cell population was established. Double staining clearly revealed that both cell fractions were not identical. Of note, A2780V cells were negative for expression of surface markers CD44 and CD117 (c-kit). When cultured on monolayers of healthy human mesothelial cells, green-fluorescence-protein (GFP)-transfected SP of A2780V exhibited spheroid-formation, whereas non-side-population (NSP) developed a spare monolayer growing over the healthy mesothelium. Furthermore, A2780V SP was found to be partially resistant to platinum. However, this resistance could not be explained by over-expression of the "excision repair cross-complementation group 1" (ERCC1) gene, which is essentially involved in the repair of platinated DNA damage. ERCC1 was, nonetheless, over-expressed in A2780V cells grown as spheres under stem cell-selective conditions as compared to adherent monolayers cultured under differentiating conditions. The same was true for

  4. Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2.

    PubMed

    Wang, Ying; Dong, Jie; Li, Dali; Lai, Li; Siwko, Stefan; Li, Yi; Liu, Mingyao

    2013-09-01

    The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1. © AlphaMed Press.

  5. Cell Cycle Regulation of Stem Cells by MicroRNAs.

    PubMed

    Mens, Michelle M J; Ghanbari, Mohsen

    2018-06-01

    MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

  6. 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

  7. 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

  8. 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.

  9. Biomechanics of stem cells

    NASA Astrophysics Data System (ADS)

    Spector, A. A.; Yuan, D.; Somers, S.; Grayson, W. L.

    2018-04-01

    Stem cells play a key role in the healthy development and maintenance of organisms. They are also critically important in medical treatments of various diseases. It has been recently demonstrated that the mechanical factors such as forces, adhesion, stiffness, relaxation, etc. have significant effects on stem cell functions. Under physiological conditions, cells (stem cells) in muscles, heart, and blood vessels are under the action of externally applied strains. We consider the stem cell microenvironment and performance associated with their conversion (differentiation) into skeletal muscle cells. Two problems are studied by using mathematical models whose parameters are then optimized by fitting experiments. First, we present our analysis of the process of stem cell differentiation under the application of cyclic unidirectional strain. This process is interpreted as a transition through several (six) stages where each of them is defined in terms of expression of a set of factors typical to skeletal muscle cells. The stem cell evolution toward muscle cells is described by a system of nonlinear ODEs. The parameters of the model are determined by fitting the experimental data on the time course of expression of the factors under consideration. Second, we analyse the mechanical (relaxation) properties of a scaffold that serves as the microenvironment for stem cells differentiation into skeletal muscle cells. This scaffold (surrounded by a liquid solution) is composed of unidirectional fibers with pores between them. The relaxation properties of the scaffold are studied in an experiment where a long cylindrical specimen is loaded by the application of ramp displacement until the strain reaches a prescribed value. The magnitude of the corresponding load is recorded. The specimen is considered as transversely isotropic poroelastic cylinder whose force relaxation is associated with liquid diffusion through the pores. An analytical solution for the total force applied to

  10. 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.

  11. Cancer stem cells, cancer cell plasticity and radiation therapy.

    PubMed

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation.

    PubMed

    Choi, Hyun Woo; Hong, Yean Ju; Kim, Jong Soo; Song, Hyuk; Cho, Ssang Gu; Bae, Hojae; Kim, Changsung; Byun, Sung June; Do, Jeong Tae

    2017-01-01

    Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Human skeletal muscle-derived stem cells retain stem cell properties after expansion in myosphere culture

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

    Wei, Yan; Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guang Zhou; Li, Yuan

    2011-04-15

    Human skeletal muscle contains an accessible adult stem-cell compartment in which differentiated myofibers are maintained and replaced by a self-renewing stem cell pool. Previously, studies using mouse models have established a critical role for resident stem cells in skeletal muscle, but little is known about this paradigm in human muscle. Here, we report the reproducible isolation of a population of cells from human skeletal muscle that is able to proliferate for extended periods of time as floating clusters of rounded cells, termed 'myospheres' or myosphere-derived progenitor cells (MDPCs). The phenotypic characteristics and functional properties of these cells were determined usingmore » reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunocytochemistry. Our results showed that these cells are clonogenic, express skeletal progenitor cell markers Pax7, ALDH1, Myod, and Desmin and the stem cell markers Nanog, Sox2, and Oct3/4 significantly elevated over controls. They could be maintained proliferatively active in vitro for more than 20 weeks and passaged at least 18 times, despite an average donor-age of 63 years. Individual clones (4.2%) derived from single cells were successfully expanded showing clonogenic potential and sustained proliferation of a subpopulation in the myospheres. Myosphere-derived cells were capable of spontaneous differentiation into myotubes in differentiation media and into other mesodermal cell lineages in induction media. We demonstrate here that direct culture and expansion of stem cells from human skeletal muscle is straightforward and reproducible with the appropriate technique. These cells may provide a viable resource of adult stem cells for future therapies of disease affecting skeletal muscle or mesenchymal lineage derived cell types.« less

  18. Intact Arabidopsis RPB1 functions in stem cell niches maintenance and cell cycling control.

    PubMed

    Zhang, Qian-Qian; Li, Ying; Fu, Zhao-Ying; Liu, Xun-Biao; Yuan, Kai; Fang, Ying; Liu, Yan; Li, Gang; Zhang, Xian-Sheng; Chong, Kang; Ge, Lei

    2018-05-12

    Plant meristem activity depends on accurate execution of transcriptional networks required for establishing optimum functioning of stem cell niches. An Arabidopsis mutant card1-1 (constitutive auxin response with DR5:GFP) that encodes a truncated RPB1 (RNA Polymerase II's largest subunit) with shortened C-terminal domain (CTD) was identified. Phosphorylation of the CTD repeats of RPB1 is coupled to transcription in eukaryotes. Here we uncover that the truncated CTD of RPB1 disturbed cell cycling and enlarged the size of shoot and root meristem. The defects in patterning of root stem cell niche in card1-1 indicates that intact CTD of RPB1 is necessary for fine-tuning the specific expression of genes responsible for cell-fate determination. The gene-edited plants with different CTD length of RPB1, created by CRISPR-CAS9 technology, confirmed that both the full length and the DK-rich tail of RPB1's CTD play roles in the accurate transcription of CYCB1;1 encoding a cell-cycle marker protein in root meristem and hence participate in maintaining root meristem size. Our experiment proves that the intact RPB1 CTD is necessary for stem cell niche maintenance, which is mediated by transcriptional regulation of cell cycling genes. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

  19. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

    NASA Astrophysics Data System (ADS)

    Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

    2015-03-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

  20. 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

  1. 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

  2. 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.

  3. Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue.

    PubMed

    Yee, Karen K; Li, Yan; Redding, Kevin M; Iwatsuki, Ken; Margolskee, Robert F; Jiang, Peihua

    2013-05-01

    Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate (CV) and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knockin allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of CV and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue. Copyright © 2013 AlphaMed Press.

  4. Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells

    PubMed Central

    Gerson, Stanton L.

    2017-01-01

    Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM), but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus. We studied PLSC linked to thymic lymphomas. In this study, we use MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of PLSC to LIC. Following BM transplantation, we found that MSH2-/- BM cells from young mice are able to fully reconstitute multiple hematopoietic lineages of lethally irradiated wild-type recipients. However, all recipients developed thymic lymphomas within three and four months post transplantation. Transplantation of different fractions of BM cells or thymocytes from young health MSH2-/- mice showed that an HSC enriched fraction always reconstituted hematopoiesis followed by lymphoma development. In addition, lymphomas did not occur in thymectomized recipients of MSH2-/- BM. These results suggest that HSCs with DNA repair defects such as MSH2-/- are PLSCs because they retain hematopoietic function, but also carry an obligate lymphomagenic potential within their T-cell progeny that is dependent on the thymic microenvironment. PMID:28767666

  5. [Stem cell therapy in cardiovascular diseases].

    PubMed

    Vértesaljai, Márton; Piróth, Zsolt; Fontos, Géza; Andréka, Gyórgy; Font, Gusztáv; Szánthó, Gergely; Réti, Marienn; Masszi, Tamás; Andréka, Peter

    2005-11-20

    Myocardial infarction is the leading cause of congestive heart failure in the industrialized world. Current treatments fail to address the underlying scarring and cell loss, which are the causes of ischaemic heart failure. Recent interest has focused on stem cells, which are undifferentiated and pluripotent cells that can proliferate, potentially self-renew, and differentiate into cardiomyocytes and endothelial cells. Myocardial regeneration is the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes were generated in what was previously considered a postmitotic organ. So far, candidates for cardiac stem cell therapy have been limited to patients with acute myocardial infarction and chronic ischaemic heart failure. Currently, bone marrow stem cells seem to be the most attractive cell type for these patients. The cells may be delivered by means of direct surgical injection, intracoronary infusion, retrograde venous infusion, and transendocardial infusion. Stem cells may directly increase cardiac contractility or passively limit infarct expansion and remodeling. Early phase I clinical studies indicate that stem cell transplantation is feasible and may have beneficial effects on ventricular remodeling after myocardial infarction. Future randomized clinical trials will establish the magnitude of benefit and the effect on mortality after stem cell therapy.

  6. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

    PubMed Central

    Chen, Song; Zhang, Wei; Wang, Ji-Ming; Duan, Hong-Tao; Kong, Jia-Hui; Wang, Yue-Xin; Dong, Meng; Bi, Xue; Song, Jian

    2016-01-01

    AIM To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC) was able to differentiate into neural stem cell and neuron in vitro. METHODS The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS), then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence (IF) analyzes. RESULTS A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2), CD73 (SH3) and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE) and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2) and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases. PMID:26949608

  7. 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

  8. Single-Cell Sequencing Technologies for Cardiac Stem Cell Studies.

    PubMed

    Liu, Tiantian; Wu, Hongjin; Wu, Shixiu; Wang, Charles

    2017-11-01

    Today with the rapid advancements in stem cell studies and the promising potential of using stem cells in clinical therapy, there is an increasing demand for in-depth comprehensive analysis on individual cell transcriptome and epigenome, as they play critical roles in a number of cell functions such as cell differentiation, growth, and reprogramming. The development of single-cell sequencing technologies has helped in revealing some exciting new perspectives in stem cells and regenerative medicine research. Among the various potential applications, single-cell analysis for cardiac stem cells (CSCs) holds tremendous promises in understanding the mechanisms of heart development and regeneration, which might light up the path toward cell therapy for cardiovascular diseases. This review briefly highlights the recent progresses in single-cell sequencing analysis technologies and their applications in CSC research.

  9. Stem cells: sources and applications.

    PubMed

    Vats, A; Tolley, N S; Polak, J M; Buttery, L D K

    2002-08-01

    Tissue engineering is a multidisciplinary area of research aimed at regeneration of tissues and restoration of function of organs through implantation of cells/tissues grown outside the body, or stimulating cells to grow into implanted matrix. In this short review, some of the most recent developments in the use of stem cells for tissue repair and regeneration will be discussed. There is no doubt that stem cells derived from adult and embryonic sources hold great therapeutic potential but it is clear that there is still much research required before their use is commonplace. There is much debate over adult versus embryonic stem cells and whether both are required. It is probably too early to disregard one or other of these cell sources. With regard to embryonic stem cells, the major concern relates to the ethics of their creation and the proposed practice of therapeutic cloning.

  10. Progress and Prospects for Stem Cell Engineering

    PubMed Central

    Ashton, Randolph S.; Keung, Albert J.; Peltier, Joseph; Schaffer, David V.

    2018-01-01

    Stem cells offer tremendous biomedical potential owing to their abilities to self-renew and differentiate into cell types of multiple adult tissues. Researchers and engineers have increasingly developed novel discovery technologies, theoretical approaches, and cell culture systems to investigate microenvironmental cues and cellular signaling events that control stem cell fate. Many of these technologies facilitate high-throughput investigation of microenvironmental signals and the intracellular signaling networks and machinery processing those signals into cell fate decisions. As our aggregate empirical knowledge of stem cell regulation grows, theoretical modeling with systems and computational biology methods has and will continue to be important for developing our ability to analyze and extract important conceptual features of stem cell regulation from complex data. Based on this body of knowledge, stem cell engineers will continue to develop technologies that predictably control stem cell fate with the ultimate goal of being able to accurately and economically scale up these systems for clinical-grade production of stem cell therapeutics. PMID:22432628

  11. Skin Stem Cells: At the Frontier Between the Laboratory and Clinical Practice. Part 1: Epidermal Stem Cells.

    PubMed

    Pastushenko, I; Prieto-Torres, L; Gilaberte, Y; Blanpain, C

    2015-11-01

    Stem cells are characterized by their ability to self-renew and differentiate into the different cell lineages of their tissue of origin. The discovery of stem cells in adult tissues, together with the description of specific markers for their isolation, has opened up new lines of investigation, expanding the horizons of biomedical research and raising new hope in the treatment of many diseases. In this article, we review in detail the main characteristics of the stem cells that produce the specialized cells of the skin (epidermal, mesenchymal, and melanocyte stem cells) and their potential implications and applications in diseases affecting the skin. Part I deals with the principal characteristics and potential applications of epidermal stem cells in dermatology. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  12. Separation technologies for stem cell bioprocessing.

    PubMed

    Diogo, Maria Margarida; da Silva, Cláudia Lobato; Cabral, Joaquim M S

    2012-11-01

    Stem cells have been the focus of an intense research due to their potential in Regenerative Medicine, drug discovery, toxicology studies, as well as for fundamental studies on developmental biology and human disease mechanisms. To fully accomplish this potential, the successful application of separation processes for the isolation and purification of stem cells and stem cell-derived cells is a crucial issue. Although separation methods have been used over the past decades for the isolation and enrichment of hematopoietic stem/progenitor cells for transplantation in hemato-oncological settings, recent achievements in the stem cell field have created new challenges including the need for novel scalable separation processes with a higher resolution and more cost-effective. Important examples are the need for high-resolution methods for the separation of heterogeneous populations of multipotent adult stem cells to study their differential biological features and clinical utility, as well as for the depletion of tumorigenic cells after pluripotent stem cell differentiation. Focusing on these challenges, this review presents a critical assessment of separation processes that have been used in the stem cell field, as well as their current and potential applications. The techniques are grouped according to the fundamental principles that govern cell separation, which are defined by the main physical, biophysical, and affinity properties of cells. A special emphasis is given to novel and promising approaches such as affinity-based methods that take advantage of the use of new ligands (e.g., aptamers, lectins), as well as to novel biophysical-based methods requiring no cell labeling and integrated with microscale technologies. Copyright © 2012 Wiley Periodicals, Inc.

  13. Stem Cells for Skeletal Muscle Tissue Engineering.

    PubMed

    Pantelic, Molly N; Larkin, Lisa M

    2018-04-19

    Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

  14. Stem cells therapy for ALS.

    PubMed

    Mazzini, Letizia; Vescovi, Angelo; Cantello, Roberto; Gelati, Maurizio; Vercelli, Alessandro

    2016-01-01

    Despite knowledge on the molecular basis of amyotrophic lateral sclerosis (ALS) having quickly progressed over the last few years, such discoveries have not yet translated into new therapeutics. With the advancement of stem cell technologies there is hope for stem cell therapeutics as novel treatments for ALS. We discuss in detail the therapeutic potential of different types of stem cells in preclinical and clinical works. Moreover, we address many open questions in clinical translation. SC therapy is a potentially promising new treatment for ALS and the need to better understand how to develop cell-based experimental treatments, and how to implement them in clinical trials, becomes more pressing. Mesenchymal stem cells and neural fetal stem cells have emerged as safe and potentially effective cell types, but there is a need to carry out appropriately designed experimental studies to verify their long-term safety and possibly efficacy. Moreover, the cost-benefit analysis of the results must take into account the quality of life of the patients as a major end point. It is our opinion that a multicenter international clinical program aime d at fine-tuning and coordinating transplantation procedures and protocols is mandatory.

  15. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    DTIC Science & Technology

    2015-07-01

    dominant role over some oncogene function.In addition, we recently reported that cancer stem cells (CSCs)- stem cell like cells in tumors that have stem ... cell properties and tumor initiating ability- retain epigenetic memories of their cells of origin (Chow et al., 2014). We showed that CSCs derived from

  16. Engineering Concepts in Stem Cell Research.

    PubMed

    Narayanan, Karthikeyan; Mishra, Sachin; Singh, Satnam; Pei, Ming; Gulyas, Balazs; Padmanabhan, Parasuraman

    2017-12-01

    The field of regenerative medicine integrates advancements made in stem cells, molecular biology, engineering, and clinical methodologies. Stem cells serve as a fundamental ingredient for therapeutic application in regenerative medicine. Apart from stem cells, engineering concepts have equally contributed to the success of stem cell based applications in improving human health. The purpose of various engineering methodologies is to develop regenerative and preventive medicine to combat various diseases and deformities. Explosion of stem cell discoveries and their implementation in clinical setting warrants new engineering concepts and new biomaterials. Biomaterials, microfluidics, and nanotechnology are the major engineering concepts used for the implementation of stem cells in regenerative medicine. Many of these engineering technologies target the specific niche of the cell for better functional capability. Controlling the niche is the key for various developmental activities leading to organogenesis and tissue homeostasis. Biomimetic understanding not only helped to improve the design of the matrices or scaffolds by incorporating suitable biological and physical components, but also ultimately aided adoption of designs that helped these materials/devices have better function. Adoption of engineering concepts in stem cell research improved overall achievement, however, several important issues such as long-term effects with respect to systems biology needs to be addressed. Here, in this review the authors will highlight some interesting breakthroughs in stem cell biology that use engineering methodologies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Non-Neuronal Release of Gamma-Aminobutyric Acid by Embryonic Pluripotent Stem Cells

    PubMed Central

    Teng, Lin; Tang, Ya-Bin; Sun, Fan; An, Shi-Min; Zhang, Chun; Yang, Xin-Jie; Lv, Hao-Yu; Lu, Qin; Cui, Yong-Yao; Hu, Jin-Jia

    2013-01-01

    γ-Aminobutyric acid (GABA), the principle inhibitory transmitter in the mature central nervous system, is also involved in activities outside the nervous system. Recent studies have shown that functional GABA receptors are expressed in embryonic stem (ES) cells and these receptors control ES cell proliferation. However, it is not clear whether ES cells have their own GABAergic transmission output machinery that can fulfill GABA release or whether the cells merely process the GABA receptors by receiving and responding to the diffused GABA released elsewhere. To get further insight into this unresolved problem, we detected the repertoire of components for GABA synthesis, storage, reaction, and termination in ES and embryonal carcinoma stem cells by biological assays, and then directly quantified released GABA in the intercellular milieu from these pluripotent stem (PS) cells by an analytical chemical assay based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). We found that embryonic PS cells processed a GABAergic circuit machinery and spontaneously released GABA, which suggests the potential that embryonic PS cells could autonomously establish a GABA niche via release of the transmitter. PMID:23799822

  18. Stem Cell Banking for Regenerative and Personalized Medicine

    PubMed Central

    Harris, David T.

    2014-01-01

    Regenerative medicine, tissue engineering and gene therapy offer the opportunity to treat and cure many of today’s intractable afflictions. These approaches to personalized medicine often utilize stem cells to accomplish these goals. However, stem cells can be negatively affected by donor variables such as age and health status at the time of collection, compromising their efficacy. Stem cell banking offers the opportunity to cryogenically preserve stem cells at their most potent state for later use in these applications. Practical stem cell sources include bone marrow, umbilical cord blood and tissue, and adipose tissue. Each of these sources contains stem cells that can be obtained from most individuals, without too much difficulty and in an economical fashion. This review will discuss the advantages and disadvantages of each stem cell source, factors to be considered when contemplating banking each stem cell source, the methodology required to bank each stem cell source, and finally, current and future clinical uses of each stem cell source. PMID:28548060

  19. When nano meets stem: the impact of nanotechnology in stem cell biology.

    PubMed

    Kaur, Savneet; Singhal, Barkha

    2012-01-01

    Nanotechnology and biomedical treatments using stem cells are among the latest conduits of biotechnological research. Even more recently, scientists have begun finding ways to mate these two specialties of science. The advent of nanotechnology has paved the way for an explicit understanding of stem cell therapy in vivo and by recapitulation of such in vivo environments in the culture, this technology seems to accommodate a great potential in providing new vistas to stem cell research. Nanotechnology carries in its wake, the development of highly stable, efficient and specific gene delivery systems for both in vitro and in vivo genetic engineering of stem cells, use of nanoscale systems (such as microarrays) for investigation of gene expression in stem cells, creation of dynamic three-dimensional nano-environments for in vitro and in vivo maintenance and differentiation of stem cells and development of extremely sensitive in vivo detection systems to gain insights into the mechanisms of stem cell differentiation and apoptosis in different disease models. The present review presents an overview of the current applications and future prospects for the use of nanotechnology in stem cell biology. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. 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.

  1. Embryonic stem cells: testing the germ-cell theory.

    PubMed

    Hochedlinger, Konrad

    2011-10-25

    The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Kidney regeneration and stem cells.

    PubMed

    Takaori, Koji; Yanagita, Motoko

    2014-01-01

    The kidney has the capacity to recover from ischemic and toxic insults. Although there has been debate about the origin of cells that replace injured epithelial cells, it is now widely recognized that intrinsic surviving tubular cells are responsible for the repair. On the other hand, the cells, which have stem cell-like characteristics, have been isolated in the kidney using various methods, but it remains unknown if these stem cells actually exist in the adult kidney and if they are involved in kidney regeneration. This review will focus on the pathophysiology of kidney regeneration and the contribution of renal stem cells. We also discuss possible therapeutic applications to kidney disease. Copyright © 2013 Wiley Periodicals, Inc.

  3. The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb.

    PubMed

    Yu, Yiqun; Moberly, Andrew H; Bhattarai, Janardhan P; Duan, Chen; Zheng, Qian; Li, Fangqi; Huang, Hugh; Olson, William; Luo, Wenqin; Wen, Tieqiao; Yu, Hongmeng; Ma, Minghong

    2017-09-27

    Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5 + cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP + cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells. SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5 + cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons. Copyright © 2017 the authors 0270-6474/17/379403-12$15.00/0.

  4. In search of adult renal stem cells.

    PubMed

    Anglani, F; Forino, M; Del Prete, D; Tosetto, E; Torregrossa, R; D'Angelo, A

    2004-01-01

    The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes - together with a knowledge of the embryonic origin of renal cells - should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

  5. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  6. Ethical Issues in Stem Cell Research

    PubMed Central

    Lo, Bernard; Parham, Lindsay

    2009-01-01

    Stem cell research offers great promise for understanding basic mechanisms of human development and differentiation, as well as the hope for new treatments for diseases such as diabetes, spinal cord injury, Parkinson’s disease, and myocardial infarction. However, human stem cell (hSC) research also raises sharp ethical and political controversies. The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood. The reprogramming of somatic cells to produce induced pluripotent stem cells avoids the ethical problems specific to embryonic stem cell research. In any hSC research, however, difficult dilemmas arise regarding sensitive downstream research, consent to donate materials for hSC research, early clinical trials of hSC therapies, and oversight of hSC research. These ethical and policy issues need to be discussed along with scientific challenges to ensure that stem cell research is carried out in an ethically appropriate manner. This article provides a critical analysis of these issues and how they are addressed in current policies. PMID:19366754

  7. Mesenchymal Stem Cells Retain Their Defining Stem Cell Characteristics After Exposure to Ionizing Radiation

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

    Nicolay, Nils H., E-mail: n.nicolay@dkfz.de; Department of Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg; Sommer, Eva

    2013-12-01

    Purpose: Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown. Methods and Materials: Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IRmore » were studied using gene arrays. Results: MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR. Conclusions: These data suggest that human MSCs are not more radiosensitive than differentiated primary fibroblasts. In addition, upon photon irradiation, MSCs were able to retain their defining stem cell characteristics both on a functional level and regarding stem cell marker expression.« less

  8. Fundamental Principles of Stem Cell Banking.

    PubMed

    Sun, Changbin; Yue, Jianhui; He, Na; Liu, Yaqiong; Zhang, Xi; Zhang, Yong

    2016-01-01

    Stem cells are highly promising resources for application in cell therapy, regenerative medicine, drug discovery, toxicology and developmental biology research. Stem cell banks have been increasingly established all over the world in order to preserve their cellular characteristics, prevent contamination and deterioration, and facilitate their effective use in basic and translational research, as well as current and future clinical application. Standardization and quality control during banking procedures are essential to allow researchers from different labs to compare their results and to develop safe and effective new therapies. Furthermore, many stem cells come from once-in-a-life time tissues. Cord blood for example, thrown away in the past, can be used to treat many diseases such as blood cancers nowadays. Meanwhile, these cells stored and often banked for long periods can be immediately available for treatment when needed and early treatment can minimize disease progression. This paper provides an overview of the fundamental principles of stem cell banking, including: (i) a general introduction of the construction and architecture commonly used for stem cell banks; (ii) a detailed section on current quality management practices; (iii) a summary of questions we should consider for long-term storage, such as how long stem cells can be stored stably, how to prevent contamination during long term storage, etc.; (iv) the prospects for stem cell banking.

  9. The continuum of stem cell transdifferentiation: possibility of hematopoietic stem cell plasticity with concurrent CD45 expression.

    PubMed

    Udani, V M

    2006-02-01

    Recent years have seen a surge of scientific research examining adult stem cell plasticity. For example, the hematopoietic stem cell has been shown to give rise to skin, respiratory epithelium, intestinal epithelium, renal epithelium, liver parenchyma, pancreas, skeletal muscle, vascular endothelium, myocardium, and central nervous system (CNS) neurons. The potential for such stem cell plasticity seems to be enhanced by stressors such as injury and neoplasia. Interestingly, recent studies have demonstrated that hematopoietic stem cells may be able to adopt certain nonhematopoietic phenotypes, such as endothelial, neural, or skeletal muscle phenotypes, without entirely losing their initial hematopoietic identity. We propose that transdifferentiation can, in certain conditions, be a partial rather than a complete event, and we encourage further investigation into the phenomenon of a stem cell simultaneously expressing phenotypic features of two distinct cell fates.

  10. Stem Cell-Like Differentiation Potentials of Endometrial Side Population Cells as Revealed by a Newly Developed In Vivo Endometrial Stem Cell Assay

    PubMed Central

    Miyazaki, Kaoru; Maruyama, Tetsuo; Masuda, Hirotaka; Yamasaki, Akiko; Uchida, Sayaka; Oda, Hideyuki; Uchida, Hiroshi; Yoshimura, Yasunori

    2012-01-01

    Background Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP), but not endometrial main population cells (EMP), exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche) to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay. Methodology/Principal Findings ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom), a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells. Conclusions/Significance We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue

  11. 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.

  12. Stem cell function during plant vascular development

    PubMed Central

    Miyashima, Shunsuke; Sebastian, Jose; Lee, Ji-Young; Helariutta, Yka

    2013-01-01

    The plant vascular system, composed of xylem and phloem, evolved to connect plant organs and transport various molecules between them. During the post-embryonic growth, these conductive tissues constitutively form from cells that are derived from a lateral meristem, commonly called procambium and cambium. Procambium/cambium contains pluripotent stem cells and provides a microenvironment that maintains the stem cell population. Because vascular plants continue to form new tissues and organs throughout their life cycle, the formation and maintenance of stem cells are crucial for plant growth and development. In this decade, there has been considerable progress in understanding the molecular control of the organization and maintenance of stem cells in vascular plants. Noticeable advance has been made in elucidating the role of transcription factors and major plant hormones in stem cell maintenance and vascular tissue differentiation. These studies suggest the shared regulatory mechanisms among various types of plant stem cell pools. In this review, we focus on two aspects of stem cell function in the vascular cambium, cell proliferation and cell differentiation. PMID:23169537

  13. In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells.

    PubMed

    Ishikura, Yukiko; Yabuta, Yukihiro; Ohta, Hiroshi; Hayashi, Katsuhiko; Nakamura, Tomonori; Okamoto, Ikuhiro; Yamamoto, Takuya; Kurimoto, Kazuki; Shirane, Kenjiro; Sasaki, Hiroyuki; Saitou, Mitinori

    2016-12-06

    The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Stem cell facelift: between reality and fiction.

    PubMed

    Atiyeh, Bishara S; Ibrahim, Amir E; Saad, Dibo A

    2013-03-01

    Stem cells are "big business" throughout medical technology, and their potential application in cosmetic procedures is no exception. One of the latest nonsurgical facial treatments (and new catchphrases) in plastic surgery is the "stem cell facelift." It is evident from the currently available scientific literature that the use of stem cell therapy for facial rejuvenation is limited to the theoretical induction of skin tightening and can in no way be equated to a facelift. In fact, what is advertised and promoted as a new and original technique of stem cell facelifting is mostly stem cell-enriched lipofilling. Despite encouraging data suggesting that adult stem cells hold promise for future applications, the data from clinical evidence available today do not substantiate the marketing and promotional claims being made to patients. To claim that the "stem cell facelift" is a complete facial rejuvenation procedure surgery is unethical.

  15. 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.

  16. A genetic framework controlling the differentiation of intestinal stem cells during regeneration in Drosophila

    PubMed Central

    Boquete, Jean-Philippe

    2017-01-01

    The speed of stem cell differentiation has to be properly coupled with self-renewal, both under basal conditions for tissue maintenance and during regeneration for tissue repair. Using the Drosophila midgut model, we analyze at the cellular and molecular levels the differentiation program required for robust regeneration. We observe that the intestinal stem cell (ISC) and its differentiating daughter, the enteroblast (EB), form extended cell-cell contacts in regenerating intestines. The contact between progenitors is stabilized by cell adhesion molecules, and can be dynamically remodeled to elicit optimal juxtacrine Notch signaling to determine the speed of progenitor differentiation. Notably, increasing the adhesion property of progenitors by expressing Connectin is sufficient to induce rapid progenitor differentiation. We further demonstrate that JAK/STAT signaling, Sox21a and GATAe form a functional relay to orchestrate EB differentiation. Thus, our study provides new insights into the complex and sequential events that are required for rapid differentiation following stem cell division during tissue replenishment. PMID:28662029

  17. 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.

  18. Intestinal stem cells and their defining niche.

    PubMed

    Tan, David Wei-Min; Barker, Nick

    2014-01-01

    The intestinal epithelium is a classic example of a rapidly self-renewing tissue fueled by dedicated resident stem cells. These stem cells reside at the crypt base, generating committed progeny that mature into the various functional epithelial lineages while following a rapid migratory path toward the villi. Two models of intestinal stem cell location were proposed half a century ago and data have been presented in support of both models, dividing the scientific community. Molecular markers have been identified and validated using new techniques such as in vivo lineage tracing and ex vivo organoid culture. The intestinal stem cell niche comprises both epithelial cells, in particular the Paneth cell, and the stromal compartment, where cell-associated ligands and soluble factors regulate stem cell behavior. This review highlights the recent advances in identifying and characterizing the intestinal stem cells and their defining niche. © 2014 Elsevier Inc. All rights reserved.

  19. Does the preference of peripheral versus central venous access in peripheral blood stem cell collection/yield change stem cell kinetics in autologous stem cell transplantation?

    PubMed

    Dogu, Mehmet Hilmi; Kaya, Ali Hakan; Berber, Ilhami; Sari, İsmail; Tekgündüz, Emre; Erkurt, Mehmet Ali; Iskender, Dicle; Kayıkçı, Ömur; Kuku, Irfan; Kaya, Emin; Keskin, Ali; Altuntaş, Fevzi

    2016-02-01

    Central venous access is often used during apheresis procedure in stem cell collection. The aim of the present study was to evaluate whether central or peripheral venous access has an effect on stem cell yield and the kinetics of the procedure and the product in patients undergoing ASCT after high dose therapy. A total of 327 patients were retrospectively reviewed. The use of peripheral venous access for stem cell yield was significantly more frequent in males compared to females (p = 0.005). Total volume of the product was significantly lower in central venous access group (p = 0.046). As being a less invasive procedure, peripheral venous access can be used for stem cell yield in eligible selected patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

    PubMed Central

    Wang, Jian-Lin; Yu, Jing-Ping; Sun, Zhi-Qiang; Sun, Su-Ping

    2014-01-01

    AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics. METHODS: A serum-free medium (SFM) suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres. A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays. Furthermore, different cells after different doses of irradiation were tested to evaluate the change in sphere formation, cell cycle and CD44+CD271+ expression of tumor stem-like spheroid cells using flow cytometry before and after irradiation. RESULTS: The cells were observed to generate an increased number of spheres in SFM with increasing cell passage. Radiation increased the rate of generation of stem-like spheres in both types of cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81 ± 0.03 vs 0.87 ± 0.01 (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69 ± 0.04 vs 0.80 ± 0.03, P < 0.05. In the esophageal parental cells, irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were resistant to irradiation-induced G2 arrest without significant changes in the percentage population of irradiated stem-like cells. Under irradiation at 0, 4, and 8 Gy, the CD44+CD271+ cell percentage for KYSE150 parental cells was 1.08% ± 0.03% vs 1.29% ± 0.07% vs 1.11% ± 0.09%, respectively; the CD44+CD271+ cell percentage for TE1 parental cells was 1.16% ± 0.11% vs 0.97% ± 0.08% vs 1.45% ± 0.35%, respectively. The differences were not statistically significant. Under irradiation at 0, 4, and 8 Gy, the CD44+CD271+ cell percentage for KYSE-150 stem

  1. Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines.

    PubMed

    Wang, Jian-Lin; Yu, Jing-Ping; Sun, Zhi-Qiang; Sun, Su-Ping

    2014-12-28

    To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics. A serum-free medium (SFM) suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres. A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays. Furthermore, different cells after different doses of irradiation were tested to evaluate the change in sphere formation, cell cycle and CD44(+)CD271(+) expression of tumor stem-like spheroid cells using flow cytometry before and after irradiation. The cells were observed to generate an increased number of spheres in SFM with increasing cell passage. Radiation increased the rate of generation of stem-like spheres in both types of cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81 ± 0.03 vs 0.87 ± 0.01 (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69 ± 0.04 vs 0.80 ± 0.03, P < 0.05. In the esophageal parental cells, irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were resistant to irradiation-induced G2 arrest without significant changes in the percentage population of irradiated stem-like cells. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE150 parental cells was 1.08% ± 0.03% vs 1.29% ± 0.07% vs 1.11% ± 0.09%, respectively; the CD44(+)CD271(+) cell percentage for TE1 parental cells was 1.16% ± 0.11% vs 0.97% ± 0.08% vs 1.45% ± 0.35%, respectively. The differences were not statistically significant. Under irradiation at 0, 4, and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE-150 stem-like spheres was

  2. Proteomics Coupled with Metabolite and Cell Wall Profiling Reveal Metabolic Processes of a Developing Rice Stem Internode

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

    Lin, Fan; Williams, Brad J.; Thangella, Padmavathi A. V.

    Internodes of grass stems function in mechanical support, transport, and, in some species, are a major sink organ for carbon in the form of cell wall polymers. This study reports cell wall composition, proteomic and metabolite analyses of the rice elongating internode. Along eight segments of the second rice internode (internode II) at booting stage, cellulose, lignin, and xylose increase as a percentage of cell wall material from the younger to the older internode segments, indicating active cell wall synthesis. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) of trypsin-digested peptides of size-fractionated proteins extracted from this internode at booting reveals 2547proteins withmore » at least two unique peptides. The dataset includes many glycosyltransferases, acyltransferases, glycosyl hydrolases, cell wall-localized proteins, and protein kinases that have or may have functions in cell wall biosynthesis or remodeling. Phospho-enrichment of the internode II peptides identified 21 unique phosphopeptides belonging to 20 phosphoproteins including an LRR-III family receptor like kinase. GO over-representation and KEGG pathway analyses highlight the abundances of internode proteins involved in biosynthetic processes, especially the synthesis of secondary metabolites such as phenylpropanoids and flavonoids. LC-MS of hot methanol-extracted secondary metabolites from internode II at four stages (elongation, early mature, mature and post mature) indicates that secondary metabolites in stems are distinct from those of roots and leaves, and differ during stem maturation. This work fills a void of knowledge of proteomics and metabolomics data for grass stems, specifically for rice, and provides baseline knowledge for more detailed studies of cell wall synthesis and other biological processes during internode development, toward improving grass agronomic properties.« less

  3. 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 ...

  4. Setting FIRES to Stem Cell Research

    ERIC Educational Resources Information Center

    Miller, Roxanne Grietz

    2005-01-01

    The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few…

  5. Review article: stem cells in human reproduction.

    PubMed

    Gargett, Caroline E

    2007-07-01

    The derivation of human embryonic stem (hES) cells heralds a new era in stem cell research, generating excitement for their therapeutic potential in regenerative medicine. Pioneering work of embryologists, developmental biologists, and reproductive medicine practitioners in in vitro fertilization clinics has facilitated hES cell research. This review summarizes current research focused on optimizing hES cell culture conditions for good manufacturing practice, directing hES cell differentiation toward trophectoderm and germ cells, and approaches used to reprogram cells for pluripotent cell derivation. The identification of germ stem cells in the testis and the recent controversy over their existence in the ovary raise the possibility of harnessing them for treating young cancer survivors. There is also the potential to harvest fetal stem cells with pluripotent cell-like properties from discarded placental tissues. The recent identification of adult stem/progenitor cell activity in the human endometrium offers a new understanding of common gynecological diseases. Discoveries resulting from research into embryonic, germ, fetal, and adult stem cells are highly relevant to human reproduction.

  6. Stem cell research in cell transplantation: sources, geopolitical influence, and transplantation.

    PubMed

    Eve, David J; Fillmore, Randolph W; Borlongan, Cesar V; Sanberg, Paul R

    2010-01-01

    If the rapidly progressing field of stem cell research reaches its full potential, successful treatments and enhanced understanding of many diseases are the likely results. However, the full potential of stem cell science will only be reached if all possible avenues can be explored and on a worldwide scale. Until 2009, the US had a highly restrictive policy on obtaining cells from human embryos and fetal tissue, a policy that pushed research toward the use of adult-derived cells. Currently, US policy is still in flux, and retrospective analysis does show the US lagging behind the rest of the world in the proportional increase in embryonic/fetal stem cell research. The majority of US studies being on either a limited number of cell lines, or on cells derived elsewhere (or funded by other sources than Federal) rather than on freshly isolated embryonic or fetal material. Neural, mesenchymal, and the mixed stem cell mononuclear fraction are the most commonly investigated types, which can generally be classified as adult-derived stem cells, although roughly half of the neural stem cells are fetal derived. Other types, such as embryonic and fat-derived stem cells, are increasing in their prominence, suggesting that new types of stem cells are still being pursued. Sixty percent of the reported stem cell studies involved transplantation, of which over three quarters were allogeneic transplants. A high proportion of the cardiovascular systems articles were on allogeneic transplants in a number of different species, including several autologous studies. A number of pharmaceutical grade stem cell products have also recently been tested and reported on. Stem cell research shows considerable promise for the treatment of a number of disorders, some of which have entered clinical trials; over the next few years it will be interesting to see how these treatments progress in the clinic.

  7. Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway.

    PubMed

    Gao, Yunhe; Cai, Aizhen; Xi, Hongqing; Li, Jiyang; Xu, Wei; Zhang, Yanmei; Zhang, Kecheng; Cui, Jianxin; Wu, Xiaosong; Wei, Bo; Chen, Lin

    2017-04-26

    Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary. Immunohistochemistry staining, western blot analysis, and quantitative reverse transcription polymerase chain reaction were used to determine the mRNA and protein expression level of RNF43 and other Wnt pathway factors. Gastric cancer stem-like cells were obtained from gastric cancer tumor and cell lines by tumorsphere culture. The adeno-associated virus system was used to upregulate RNF43 expression in cancer cells. Functional experiments including tumorsphere formation, chemotherapy resistance, surface marker detection, and tumor xenograft assay were performed to measure stem-like properties in gastric cancer stem-like cells after RNF43 overexpression. RNF43 loss was significantly associated with TNM stage, distant metastasis, and Lauren classification, and predicted worse prognosis in gastric cancer patients. RNF43 expression was even lower in tumorspheres derived from tumor tissues or cell lines compared with adherent cancer cells and normal gastric cells. Overexpression of RNF43 in gastric cancer cells impaired their stem-like properties, including sphere formation ability, chemoresistance in vitro, and tumorigenicity in vivo. Moreover, Wnt pathway-related proteins were decreased in RNF43-overexpressing cells, while Wnt pathway activators could reverse the trend to some extent. Our findings indicated that RNF43 might not only participate in gastric cancer progression, but also attenuate the stemness of gastric cancer stem-like cells through

  8. Adult Stem Cells and Diseases of Aging

    PubMed Central

    Boyette, Lisa B.; Tuan, Rocky S.

    2014-01-01

    Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan. PMID:24757526

  9. Clinical grade adult stem cell banking

    PubMed Central

    Thirumala, Sreedhar; Goebel, W Scott

    2009-01-01

    There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

  10. A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells

    PubMed Central

    Chen, Ling; Kasai, Tomonari; Li, Yueguang; Sugii, Yuh; Jin, Guoliang; Okada, Masashi; Vaidyanath, Arun; Mizutani, Akifumi; Satoh, Ayano; Kudoh, Takayuki; Hendrix, Mary J. C.; Salomon, David S.; Fu, Li; Seno, Masaharu

    2012-01-01

    Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5′-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model. PMID:22511923

  11. Bone marrow (stem cell) donation

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000839.htm Bone marrow (stem cell) donation To use the sharing features on this page, please enable ... cells are more likely to help patients than stem cells from older people. People who register must either: Use a cotton swab to take a sample of ...

  12. 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

  13. Live imaging of the Drosophila spermatogonial stem cell niche reveals novel mechanisms regulating germline stem cell output

    PubMed Central

    Sheng, X. Rebecca; Matunis, Erika

    2011-01-01

    Adult stem cells modulate their output by varying between symmetric and asymmetric divisions, but have rarely been observed in living intact tissues. Germline stem cells (GSCs) in the Drosophila testis are anchored to somatic hub cells and were thought to exclusively undergo oriented asymmetric divisions, producing one stem cell that remains hub-anchored and one daughter cell displaced out of the stem cell-maintaining micro-environment (niche). We developed extended live imaging of the Drosophila testis niche, allowing us to track individual germline cells. Surprisingly, new wild-type GSCs are generated in the niche during steady-state tissue maintenance by a previously undetected event we term `symmetric renewal', where interconnected GSC-daughter cell pairs swivel such that both cells contact the hub. We also captured GSCs undergoing direct differentiation by detaching from the hub. Following starvation-induced GSC loss, GSC numbers are restored by symmetric renewals. Furthermore, upon more severe (genetically induced) GSC loss, both symmetric renewal and de-differentiation (where interconnected spermatogonia fragment into pairs while moving towards then establishing contact with the hub) occur simultaneously to replenish the GSC pool. Thus, stereotypically oriented stem cell divisions are not always correlated with an asymmetric outcome in cell fate, and changes in stem cell output are governed by altered signals in response to tissue requirements. PMID:21752931

  14. Nanotopography Promotes Pancreatic Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.

    PubMed

    Kim, Jong Hyun; Kim, Hyung Woo; Cha, Kyoung Je; Han, Jiyou; Jang, Yu Jin; Kim, Dong Sung; Kim, Jong-Hoon

    2016-03-22

    Although previous studies suggest that nanotopographical features influence properties and behaviors of stem cells, only a few studies have attempted to derive clinically useful somatic cells from human pluripotent stem cells using nanopatterned surfaces. In the present study, we report that polystyrene nanopore-patterned surfaces significantly promote the pancreatic differentiation of human embryonic and induced pluripotent stem cells. We compared different diameters of nanopores and showed that 200 nm nanopore-patterned surfaces highly upregulated the expression of PDX1, a critical transcription factor for pancreatic development, leading to an approximately 3-fold increase in the percentage of differentiating PDX1(+) pancreatic progenitors compared with control flat surfaces. Furthermore, in the presence of biochemical factors, 200 nm nanopore-patterned surfaces profoundly enhanced the derivation of pancreatic endocrine cells producing insulin, glucagon, or somatostatin. We also demonstrate that nanopore-patterned surface-induced upregulation of PDX1 is associated with downregulation of TAZ, suggesting the potential role of TAZ in nanopore-patterned surface-mediated mechanotransduction. Our study suggests that appropriate cytokine treatments combined with nanotopographical stimulation could be a powerful tool for deriving a high purity of desired cells from human pluripotent stem cells.

  15. 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.

  16. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

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

    Hamada, Shin; Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp; Takikawa, Tetsuya

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression ofmore » pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.« less

  17. Steady advance of stem cell therapies: report from the 2011 World Stem Cell Summit, Pasadena, California, October 3-5.

    PubMed

    Swan, Melanie

    2011-12-01

    Stem cell research and related therapies (including regenerative medicine and cellular therapies) could have a significant near-term impact on worldwide public health and aging. One reason is the industry's strong linkage between policy, science, industry, and patient advocacy, as was clear in the attendance and programming at the 7(th) annual World Stem Cell Summit held in Pasadena, California, October 3-5, 2011. A special conference session sponsored by the SENS Foundation discussed how stem cell therapies are being used to extend healthy life span. Stem cells are useful not only in cell-replacement therapies, but also in disease modeling, drug discovery, and drug toxicity screening. Stem cell therapies are currently being applied to over 50 diseases, including heart, lung, neurodegenerative, and eye disease, cancer, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Dozens of companies are developing therapeutic solutions that are in different stages of clinical use and clinical trials. Some high-profile therapies include Dendreon's Provenge for prostate cancer, Geron's first-ever embryonic stem cell trials for spinal cord injury, Fibrocell's laViv cellular therapy for wrinkles, and well-established commercial skin substitutes (Organogenesis' Apligraf and Advanced BioHealing's Dermagraft). Stem cell policy issues under consideration include medical tourism, standards for large-scale stem cell manufacturing, and lingering ethical debates over the use of embryonic stem cells. Contemporary stem cell science advances include a focus on techniques for the direct reprogramming of cells from one lineage to another without returning to pluripotency as an intermediary step, improved means of generating and characterizing induced pluripotent cells, and progress in approaches to neurodegenerative disease.

  18. Could drugs inhibiting the mevalonate pathway also target cancer stem cells?

    PubMed

    Likus, Wirginia; Siemianowicz, Krzysztof; Bieńk, Konrad; Pakuła, Małgorzata; Pathak, Himani; Dutta, Chhanda; Wang, Qiong; Shojaei, Shahla; Assaraf, Yehuda G; Ghavami, Saeid; Cieślar-Pobuda, Artur; Łos, Marek J

    2016-03-01

    Understanding the connection between metabolic pathways and cancer is very important for the development of new therapeutic approaches based on regulatory enzymes in pathways associated with tumorigenesis. The mevalonate cascade and its rate-liming enzyme HMG CoA-reductase has recently drawn the attention of cancer researchers because strong evidences arising mostly from epidemiologic studies, show that it could promote transformation. Hence, these studies pinpoint HMG CoA-reductase as a candidate proto-oncogene. Several recent epidemiological studies, in different populations, have proven that statins are beneficial for the treatment-outcome of various cancers, and may improve common cancer therapy strategies involving alkylating agents, and antimetabolites. Cancer stem cells/cancer initiating cells (CSC) are key to cancer progression and metastasis. Therefore, in the current review we address the different effects of statins on cancer stem cells. The mevalonate cascade is among the most pleiotropic, and highly interconnected signaling pathways. Through G-protein-coupled receptors (GRCP), it integrates extra-, and intracellular signals. The mevalonate pathway is implicated in cell stemness, cell proliferation, and organ size regulation through the Hippo pathway (e.g. Yap/Taz signaling axis). This pathway is a prime preventive target through the administration of statins for the prophylaxis of obesity-related cardiovascular diseases. Its prominent role in regulation of cell growth and stemness also invokes its role in cancer development and progression. The mevalonate pathway affects cancer metastasis in several ways by: (i) affecting epithelial-to-mesenchymal transition (EMT), (ii) affecting remodeling of the cytoskeleton as well as cell motility, (iii) affecting cell polarity (non-canonical Wnt/planar pathway), and (iv) modulation of mesenchymal-to-epithelial transition (MET). Herein we provide an overview of the mevalonate signaling network. We then briefly

  19. [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.

  20. Effects of nanotopography on stem cell phenotypes.

    PubMed

    Ravichandran, Rajeswari; Liao, Susan; Ng, Clarisse Ch; Chan, Casey K; Raghunath, Michael; Ramakrishna, Seeram

    2009-12-31

    Stem cells are unspecialized cells that can self renew indefinitely and differentiate into several somatic cells given the correct environmental cues. In the stem cell niche, stem cell-extracellular matrix (ECM) interactions are crucial for different cellular functions, such as adhesion, proliferation, and differentiation. Recently, in addition to chemical surface modifications, the importance of nanometric scale surface topography and roughness of biomaterials has increasingly becoming recognized as a crucial factor for cell survival and host tissue acceptance in synthetic ECMs. This review describes the influence of nanotopography on stem cell phenotypes.

  1. Nanotechniques Inactivate Cancer Stem Cells

    NASA Astrophysics Data System (ADS)

    Goltsev, Anatoliy N.; Babenko, Natalya N.; Gaevskaya, Yulia A.; Bondarovich, Nikolay A.; Dubrava, Tatiana G.; Ostankov, Maksim V.; Chelombitko, Olga V.; Malyukin, Yuriy V.; Klochkov, Vladimir K.; Kavok, Nataliya S.

    2017-06-01

    One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.

  2. Oxygen transport and stem cell aggregation in stirred-suspension bioreactor cultures.

    PubMed

    Wu, Jincheng; Rostami, Mahboubeh Rahmati; Cadavid Olaya, Diana P; Tzanakakis, Emmanuel S

    2014-01-01

    Stirred-suspension bioreactors are a promising modality for large-scale culture of 3D aggregates of pluripotent stem cells and their progeny. Yet, cells within these clusters experience limitations in the transfer of factors and particularly O2 which is characterized by low solubility in aqueous media. Cultured stem cells under different O2 levels may exhibit significantly different proliferation, viability and differentiation potential. Here, a transient diffusion-reaction model was built encompassing the size distribution and ultrastructural characteristics of embryonic stem cell (ESC) aggregates. The model was coupled to experimental data from bioreactor and static cultures for extracting the effective diffusivity and kinetics of consumption of O2 within mouse (mESC) and human ESC (hESC) clusters. Under agitation, mESC aggregates exhibited a higher maximum consumption rate than hESC aggregates. Moreover, the reaction-diffusion model was integrated with a population balance equation (PBE) for the temporal distribution of ESC clusters changing due to aggregation and cell proliferation. Hypoxia was found to be negligible for ESCs with a smaller radius than 100 µm but became appreciable for aggregates larger than 300 µm. The integrated model not only captured the O2 profile both in the bioreactor bulk and inside ESC aggregates but also led to the calculation of the duration that fractions of cells experience a certain range of O2 concentrations. The approach described in this study can be employed for gaining a deeper understanding of the effects of O2 on the physiology of stem cells organized in 3D structures. Such frameworks can be extended to encompass the spatial and temporal availability of nutrients and differentiation factors and facilitate the design and control of relevant bioprocesses for the production of stem cell therapeutics.

  3. Optimizing autologous cell grafts to improve stem cell gene therapy.

    PubMed

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  4. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  5. Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells.

    PubMed

    Miszta-Lane, Helena; Mirbolooki, Mohammadreza; James Shapiro, A M; Lakey, Jonathan R T

    2006-01-01

    Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.

  6. Prion potency in stem cells biology.

    PubMed

    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  7. Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo

    PubMed Central

    Ren, Wenwen; Lewandowski, Brian C.; Watson, Jaime; Aihara, Eitaro; Iwatsuki, Ken; Bachmanov, Alexander A.; Margolskee, Robert F.; Jiang, Peihua

    2014-01-01

    Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5+) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5+ or Lgr6+ cells from taste tissue can generate continuously expanding 3D structures (“organoids”). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2’-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5+ cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6+ cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5+ or Lgr6+ cells, validating the use of this model for the study of taste cell generation. PMID:25368147

  8. Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo.

    PubMed

    Ren, Wenwen; Lewandowski, Brian C; Watson, Jaime; Aihara, Eitaro; Iwatsuki, Ken; Bachmanov, Alexander A; Margolskee, Robert F; Jiang, Peihua

    2014-11-18

    Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5(+)) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5(+) or Lgr6(+) cells from taste tissue can generate continuously expanding 3D structures ("organoids"). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2'-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5(+) cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6(+) cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5(+) or Lgr6(+) cells, validating the use of this model for the study of taste cell generation.

  9. 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.

  10. 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.

  11. [Genetic regulation of plant shoot stem cells].

    PubMed

    Al'bert, E V; Ezhova, T A

    2013-02-01

    This article describes the main features of plant stem cells and summarizes the results of studies of the genetic control of stem cell maintenance in the apical meristem of the shoot. It is demonstrated that the WUS-CLV gene system plays a key role in the maintenance of shoot apical stem cells and the formation of adventitious buds and somatic embryos. Unconventional concepts of plant stem cells are considered.

  12. Plant stem cells as innovation in cosmetics.

    PubMed

    Moruś, Martyna; Baran, Monika; Rost-Roszkowska, Magdalena; Skotnicka-Graca, Urszula

    2014-01-01

    The stem cells thanks to their ability of unlimited division number or transformation into different cell types creating organs, are responsible for regeneration processes. Depending on the organism in which the stem cells exists, they divide to the plant or animal ones. The later group includes the stem cells existing in both embryo's and adult human's organs. It includes, among others, epidermal stem cells, located in the hair follicle relieves and also in its basal layers, and responsible for permanent regeneration of the epidermis. Temporary science looks for method suitable for stimulation of the epidermis stem cells, amongst the other by delivery of e.g., growth factors for proliferation that decrease with the age. One of the methods is the use of the plant cell culture technology, including a number of methods that should ensure growth of plant cells, issues or organs in the environment with the microorganism-free medium. It uses abilities of the different plant cells to dedifferentiation into stem cells and coming back to the pluripotent status. The extracts obtained this way from the plant stem cells are currently used for production of both common or professional care cosmetics. This work describes exactly impact of the plant stem cell extract, coming from one type of the common apple tree (Uttwiler Spätlauber) to human skin as one of the first plant sorts, which are used in cosmetology and esthetic dermatology.

  13. Stem cell treatment of degenerative eye disease.

    PubMed

    Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A H; Leadbeater, Wendy; Scheven, Ben A

    2015-05-01

    Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. Copyright © 2015. Published by Elsevier B.V.

  14. Importance of the stem cell microenvironment for ophthalmological cell-based therapy

    PubMed Central

    Wan, Peng-Xia; Wang, Bo-Wen; Wang, Zhi-Chong

    2015-01-01

    Cell therapy is a promising treatment for diseases that are caused by cell degeneration or death. The cells for clinical transplantation are usually obtained by culturing healthy allogeneic or exogenous tissue in vitro. However, for diseases of the eye, obtaining the adequate number of cells for clinical transplantation is difficult due to the small size of tissue donors and the frequent needs of long-term amplification of cells in vitro, which results in low cell viability after transplantation. In addition, the transplanted cells often develop fibrosis or degrade and have very low survival. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS) are also promising candidates for cell therapy. Unfortunately, the differentiation of ESCs can bring immune rejection, tumorigenicity and undesired differentiated cells, limiting its clinical application. Although iPS cells can avoid the risk of immune rejection caused by ES cell differentiation post-transplantation, the low conversion rate, the risk of tumor formation and the potentially unpredictable biological changes that could occur through genetic manipulation hinder its clinical application. Thus, the desired clinical effect of cell therapy is impaired by these factors. Recent research findings recognize that the reason for low survival of the implanted cells not only depends on the seeded cells, but also on the cell microenvironment, which determines the cell survival, proliferation and even reverse differentiation. When used for cell therapy, the transplanted cells need a specific three-dimensional structure to anchor and specific extra cellular matrix components in addition to relevant cytokine signaling to transfer the required information to support their growth. These structures present in the matrix in which the stem cells reside are known as the stem cell microenvironment. The microenvironment interaction with the stem cells provides the necessary homeostasis for cell maintenance and growth. A

  15. 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

  16. HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells.

    PubMed

    Colamaio, Marianna; Tosti, Nadia; Puca, Francesca; Mari, Alessia; Gattordo, Rosaria; Kuzay, Yalçın; Federico, Antonella; Pepe, Anna; Sarnataro, Daniela; Ragozzino, Elvira; Raia, Maddalena; Hirata, Hidenari; Gemei, Marica; Mimori, Koshi; Del Vecchio, Luigi; Battista, Sabrina; Fusco, Alfredo

    2016-10-01

    Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.

  17. Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants.

    PubMed

    Goren Sahin, Deniz; Arat, Mutlu

    2017-12-01

    Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years' experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center. Two hundred and seven consecutive patients who underwent allogeneic peripheral blood stem cell transplantation were included in this study. Age, sex, weight, complete blood counts, CD34 + cell counts, total collected amount of CD34 + cells, CD34 + cells per 10l processed, mobilization failure and adverse events were reviewed. Median age was 40.2±12.9 (21-68) years and 46.4±13.4 (17-67) years for donors and patients, respectively. The number of donors who had undergone adequate CD34 + cell harvesting and completed the procedure on the fourth day was 67 (32.8% of all patients). Only 12 patients required cell apheresis both on day 5 and 6. Apheresis was completed on day 4 and/or day 5 in 94.2% of all our donors. There was no significant association between CD34 + stem cell volume and age, gender and weight values of donors. Mobilization failure was not seen in our series. G-CSF is highly effective in 1/3 of the donors on the 4th day in order to collect enough number of stem cells. We propose that peripheral stem cell collection might start on day 4th of G-CSF treatment for avoiding G-CSF related side effects and complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy.

    PubMed

    do Amaral, Ronaldo J F C; Almeida, Henrique V; Kelly, Daniel J; O'Brien, Fergal J; Kearney, Cathal J

    2017-01-01

    The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells.

  19. Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy

    PubMed Central

    Almeida, Henrique V.; Kelly, Daniel J.; O'Brien, Fergal J.; Kearney, Cathal J.

    2017-01-01

    The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells. PMID:29018484

  20. 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.

  1. Stem Cell-Based Therapies for Polyglutamine Diseases.

    PubMed

    Mendonça, Liliana S; Onofre, Isabel; Miranda, Catarina Oliveira; Perfeito, Rita; Nóbrega, Clévio; de Almeida, Luís Pereira

    2018-01-01

    Polyglutamine (polyQ) diseases are a family of neurodegenerative disorders with very heterogeneous clinical presentations, although with common features such as progressive neuronal death. Thus, at the time of diagnosis patients might present an extensive and irreversible neuronal death demanding cell replacement or support provided by cell-based therapies. For this purpose stem cells, which include diverse populations ranging from embryonic stem cells (ESCs), to fetal stem cells, mesenchymal stromal cells (MSCs) or induced pluripotent stem cells (iPSCs) have remarkable potential to promote extensive brain regeneration and recovery in neurodegenerative disorders. This regenerative potential has been demonstrated in exciting pre and clinical assays. However, despite these promising results, several drawbacks are hampering their successful clinical implementation. Problems related to ethical issues, quality control of the cells used and the lack of reliable models for the efficacy assessment of human stem cells. In this chapter the main advantages and disadvantages of the available sources of stem cells as well as their efficacy and potential to improve disease outcomes are discussed.

  2. In vivo stem cell tracking with imageable nanoparticles that bind bioorthogonal chemical receptors on the stem cell surface.

    PubMed

    Lee, Sangmin; Yoon, Hwa In; Na, Jin Hee; Jeon, Sangmin; Lim, Seungho; Koo, Heebeom; Han, Sang-Soo; Kang, Sun-Woong; Park, Soon-Jung; Moon, Sung-Hwan; Park, Jae Hyung; Cho, Yong Woo; Kim, Byung-Soo; Kim, Sang Kyoon; Lee, Taekwan; Kim, Dongkyu; Lee, Seulki; Pomper, Martin G; Kwon, Ick Chan; Kim, Kwangmeyung

    2017-09-01

    It is urgently necessary to develop reliable non-invasive stem cell imaging technology for tracking the in vivo fate of transplanted stem cells in living subjects. Herein, we developed a simple and well controlled stem cell imaging method through a combination of metabolic glycoengineering and bioorthogonal copper-free click chemistry. Firstly, the exogenous chemical receptors containing azide (-N 3 ) groups were generated on the surfaces of stem cells through metabolic glycoengineering using metabolic precursor, tetra-acetylated N-azidoacetyl-d-mannosamine(Ac 4 ManNAz). Next, bicyclo[6.1.0]nonyne-modified glycol chitosan nanoparticles (BCN-CNPs) were prepared as imageable nanoparticles to deliver different imaging agents. Cy5.5, iron oxide nanoparticles and gold nanoparticles were conjugated or encapsulated to BCN-CNPs for optical, MR and CT imaging, respectively. These imageable nanoparticles bound chemical receptors on the Ac 4 ManNAz-treated stem cell surface specifically via bioorthogonal copper-free click chemistry. Then they were rapidly taken up by the cell membrane turn-over mechanism resulting in higher endocytic capacity compared non-specific uptake of nanoparticles. During in vivo animal test, BCN-CNP-Cy5.5-labeled stem cells could be continuously tracked by non-invasive optical imaging over 15 days. Furthermore, BCN-CNP-IRON- and BCN-CNP-GOLD-labeled stem cells could be efficiently visualized using in vivo MR and CT imaging demonstrating utility of our stem cell labeling method using chemical receptors. These results conclude that our method based on metabolic glycoengineering and bioorthogonal copper-free click chemistry can stably label stem cells with diverse imageable nanoparticles representing great potential as new stem cell imaging technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Mesenchymal Stem Cell Fate: Applying Biomaterials for Control of Stem Cell Behavior

    PubMed Central

    Anderson, Hilary J.; Sahoo, Jugal Kishore; Ulijn, Rein V.; Dalby, Matthew J.

    2016-01-01

    The materials pipeline for biomaterials and tissue engineering applications is under continuous development. Specifically, there is great interest in the use of designed materials in the stem cell arena as materials can be used to manipulate the cells providing control of behavior. This is important as the ability to “engineer” complexity and subsequent in vitro growth of tissues and organs is a key objective for tissue engineers. This review will describe the nature of the materials strategies, both static and dynamic, and their influence specifically on mesenchymal stem cell fate. PMID:27242999

  4. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    DTIC Science & Technology

    2017-09-01

    AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...CA130273 - Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM...hypothesis, we originally proposed to transform neural stem cells (NSCs) and neural progenitor cells (NPCs) in vivo by expressing an activated form

  5. Stem cell banking: between traceability and identifiability

    PubMed Central

    2010-01-01

    Stem cell banks are increasingly seen as an essential resource of biological materials for both basic and translational research. Stem cell banks support transnational access to quality-controlled and ethically sourced stem cell lines from different origins and of varying grades. According to the Organisation for Economic Co-operation and Development, advances in regenerative medicine are leading to the development of a bioeconomy, 'a world where biotechnology contributes to a significant share of economic output'. Consequently, stem cell banks are destined to constitute a pillar of the bioeconomy in many countries. While certain ethical and legal concerns are specific to the nature of stem cells, stem cell banking could do well to examine the approaches fostered by tissue banking generally. Indeed, the past decade has seen a move to simplify and harmonize biological tissue and data banking so as to foster international interoperability. In particular, the issues of consent and of traceability illustrate not only commonalities but the opportunity for stem cell banking to appreciate the lessons learned in biobanking generally. This paper analyzes convergence and divergence in issues surrounding policy harmonization, transnational sharing, informed consent, traceability and return of results in the context of stem cell banks. PMID:20923580

  6. Stem Cell-Based Therapies for Epidermolysis Bullosa

    DTIC Science & Technology

    2014-10-01

    of human hematopoietic cells for extracellular matrix protein deficiency in epidermolysis bullosa. Stem Cells 2011, 29:900–906. 18. Di Nicola M...promotes cardiogenic gene expression in mesenchymal stem cells. Stem Cell Res Ther 2013, 4:43. 57. Herrmann JL, Wang Y, Abarbanell AM, Weil BR, Tan J

  7. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  8. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease.

    PubMed

    Fox, Ira J; Daley, George Q; Goldman, Steven A; Huard, Johnny; Kamp, Timothy J; Trucco, Massimo

    2014-08-22

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies. Copyright © 2014, American Association for the Advancement of Science.

  9. 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.

  10. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    DTIC Science & Technology

    2012-07-01

    Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

  11. Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and Metabolism on Stem Cell Potency Loss and Miscarriage.

    PubMed

    Yang, Yu; Bolnick, Alan; Shamir, Alexandra; Abdulhasan, Mohammed; Li, Quanwen; Parker, G C; Puscheck, Elizabeth E; Rappolee, D A

    2017-08-01

    Data from in vitro and in vivo models suggest that malnutrition and stress trigger adaptive responses, leading to small for gestational age (SGA) blastocysts with fewer cell numbers. These stress responses are initially adaptive, but become maladaptive with increasing stress exposures. The common stress responses of the blastocyst-derived stem cells, pluripotent embryonic and multipotent placental trophoblast stem cells (ESCs and TSCs), are decreased growth and potency, and increased, imbalanced and irreversible differentiation. SGA embryos may fail to produce sufficient antiluteolytic placental hormone to maintain corpus luteum progesterone secretion that provides nutrition at the implantation site. Myriad stress inputs for the stem cells in the embryo can occur in vitro during in vitro fertilization/assisted reproductive technology (IVF/ART) or in vivo. Paradoxically, stresses that diminish stem cell growth lead to a higher level of differentiation simultaneously which further decreases ESC or TSC numbers in an attempt to functionally compensate for fewer cells. In addition, prolonged or strong stress can cause irreversible differentiation. Resultant stem cell depletion is proposed as a cause of miscarriage via a "quiet" death of an ostensibly adaptive response of stem cells instead of a reactive, violent loss of stem cells or their differentiated progenies.

  12. 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.

  13. Applications of stem cell biology to oculoplastic surgery.

    PubMed

    Daniel, Michael G; Wu, Albert Y

    2016-09-01

    The review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery. The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in-vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte-derived stem cells offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery. The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through induced pluripotent stem cells differentiation, permitting their use in transplants for oculoplastic surgery.

  14. Odontogenic epithelial stem cells: hidden sources.

    PubMed

    Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh

    2015-12-01

    The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed.

  15. 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

  16. Droplet Microarray Based on Patterned Superhydrophobic Surfaces Prevents Stem Cell Differentiation and Enables High-Throughput Stem Cell Screening.

    PubMed

    Tronser, Tina; Popova, Anna A; Jaggy, Mona; Bastmeyer, Martin; Levkin, Pavel A

    2017-12-01

    Over the past decades, stem cells have attracted growing interest in fundamental biological and biomedical research as well as in regenerative medicine, due to their unique ability to self-renew and differentiate into various cell types. Long-term maintenance of the self-renewal ability and inhibition of spontaneous differentiation, however, still remain challenging and are not fully understood. Uncontrolled spontaneous differentiation of stem cells makes high-throughput screening of stem cells also difficult. This further hinders investigation of the underlying mechanisms of stem cell differentiation and the factors that might affect it. In this work, a dual functionality of nanoporous superhydrophobic-hydrophilic micropatterns is demonstrated in their ability to inhibit differentiation of mouse embryonic stem cells (mESCs) and at the same time enable formation of arrays of microdroplets (droplet microarray) via the effect of discontinuous dewetting. Such combination makes high-throughput screening of undifferentiated mouse embryonic stem cells possible. The droplet microarray is used to investigate the development, differentiation, and maintenance of stemness of mESC, revealing the dependence of stem cell behavior on droplet volume in nano- and microliter scale. The inhibition of spontaneous differentiation of mESCs cultured on the droplet microarray for up to 72 h is observed. In addition, up to fourfold increased cell growth rate of mESCs cultured on our platform has been observed. The difference in the behavior of mESCs is attributed to the porosity and roughness of the polymer surface. This work demonstrates that the droplet microarray possesses the potential for the screening of mESCs under conditions of prolonged inhibition of stem cells' spontaneous differentiation. Such a platform can be useful for applications in the field of stem cell research, pharmacological testing of drug efficacy and toxicity, biomedical research as well as in the field of

  17. Stem Cells and Calcium Signaling

    PubMed Central

    Tonelli, Fernanda M.P.; Santos, Anderson K.; Gomes, Dawidson A.; da Silva, Saulo L.; Gomes, Katia N.; Ladeira, Luiz O.

    2014-01-01

    The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca2+ concentration [Ca2+]i. Acting as an intracellular messenger, Ca2+ has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca2+-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential. PMID:22453975

  18. Stem cells and calcium signaling.

    PubMed

    Tonelli, Fernanda M P; Santos, Anderson K; Gomes, Dawidson A; da Silva, Saulo L; Gomes, Katia N; Ladeira, Luiz O; Resende, Rodrigo R

    2012-01-01

    The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca(2+) concentration [Ca(2+)](i). Acting as an intracellular messenger, Ca(2+) has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca(2+)-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential.

  19. 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.

  20. 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.

  1. Stem cell bioprocessing: fundamentals and principles.

    PubMed

    Placzek, Mark R; Chung, I-Ming; Macedo, Hugo M; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Cha, Jae Min; Fauzi, Iliana; Kang, Yunyi; Yeo, David C L; Ma, Chi Yip Joan; Polak, Julia M; Panoskaltsis, Nicki; Mantalaris, Athanasios

    2009-03-06

    In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the 'omics' technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical-failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications.

  2. 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...

  3. 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

  4. Mesenchymal Stem Cells Derived from Human Limbal Niche Cells

    PubMed Central

    Li, Gui-Gang; Zhu, Ying-Ting; Xie, Hua-Tao; Chen, Szu-Yu; Tseng, Scheffer C. G.

    2012-01-01

    Purpose. We investigated whether human limbal niche cells generate mesenchymal stem cells. Methods. Limbal niche cells were isolated from the limbal stroma by collagenase alone or following dispase removal of the limbal epithelium (D/C), and cultured on plastic in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS), or coated or three-dimensional Matrigel in embryonic stem cell medium with leukemia inhibitory factor and basic fibroblast growth factor. Expression of cell markers, colony-forming units-fibroblast, tri-lineage differentiation, and ability of supporting limbal epithelial stem/progenitor cells were compared to limbal residual stromal cells. Results. Stromal cells expressing angiogenesis markers were found perivascularly, subjacent to limbal basal epithelial cells, and in D/C and limbal residual stromal cells. When seeded in three-dimensional Matrigel, D/C but not limbal residual stromal cells yielded spheres of angiogenesis progenitors that stabilized vascular networks. Similar to collagenase-isolated cells, D/C cells could be expanded on coated Matrigel for more than 12 passages, yielding spindle cells expressing angiogenesis and mesenchymal stem cells markers, and possessing significantly higher colony-forming units-fibroblast and more efficient tri-lineage differentiation than D/C and limbal residual stromal cells expanded on plastic in DMEM with 10% FBS, of which both lost the pericyte phenotype while limbal residual stromal cells turned into myofibroblasts. Upon reunion with limbal epithelial stem/progenitor cells to form spheres, D/C cells expanded on coated Matrigel maintained higher expression of p63α and lower expression of cytokeratin 12 than those expanded on plastic in DMEM with 10% FBS, while spheres formed with human corneal fibroblasts expressed cytokeratin 12 without p63α. Conclusions. In the limbal stroma, cells subjacent to limbal basal epithelial cells serve as niche cells, and generate progenitors with

  5. 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.

  6. 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.

  7. 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

  8. Spermatogonial stem cell regulation and spermatogenesis

    PubMed Central

    Phillips, Bart T.; Gassei, Kathrin; Orwig, Kyle E.

    2010-01-01

    This article will provide an updated review of spermatogonial stem cells and their role in maintaining the spermatogenic lineage. Experimental tools used to study spermatogonial stem cells (SSCs) will be described, along with research using these tools to enhance our understanding of stem cell biology and spermatogenesis. Increased knowledge about the biology of SSCs improves our capacity to manipulate these cells for practical application. The chapter concludes with a discussion of future directions for fundamental investigation and practical applications of SSCs. PMID:20403877

  9. 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.

  10. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Boadi, Joseph; Matcher, Stephen; MacNeil, Sheila; Sangwan, Virender S.

    2016-04-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells are continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. In the event that the cornea is damaged and the limbal stem cell population is severely reduced, this condition known as Limbal Stem Cell Deficiency and can lead to blindness. There are numerous treatments but most have high long term failure rates. Most treatment methods include the transplantation of limbal stem cells into damaged limbus with hope of repopulating the region and regenerating at healthy corneal epithelium. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images. A bespoke OCT has been built to investigate the trajectories of these limbal stem cells after transplantation to see whether if they do repopulate the damaged limbus or not. In the experimentation magneto-labelling was used to track the limbal stem cells. For the magneto-labelling a mixture of limbal stem cells and cornea epithelium are cultured with super paramagnetic iron (Fe3O4) nanoparticles (20-30nm in size) for 24hours, to allow for uptake. The cells are then transplanted onto the denuded cornea. The transplanted cell mixture with the encapsulated magnetic nanoparticles is actuated with an external magnetic field 0.08T leading to a phase modulation on the signal. A Phase sensitive Magneto-motive OCT is used to locate the transplanted cells. The location of the cells with embed SPIOs were located both in 2D and 3D.

  11. Biophysical regulation of stem cell differentiation.

    PubMed

    Govey, Peter M; Loiselle, Alayna E; Donahue, Henry J

    2013-06-01

    Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

  12. Colon Stem Cell and Crypt Dynamics Exposed by Cell Lineage Reconstruction

    PubMed Central

    Itzkovitz, Shalev; Elbaz, Judith; Maruvka, Yosef E.; Segev, Elad; Shlush, Liran I.; Dekel, Nava; Shapiro, Ehud

    2011-01-01

    Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems. PMID:21829376

  13. Stem-cell Based Therapies for Epidermolysis Bullosa

    DTIC Science & Technology

    2013-10-01

    This application addresses the FY11 PRMRP Topic Area, Epidermolysis Bullosa, and proposes to develop stem - cell based therapies for junctional...accomplish this goal, we are proposing to develop stem - cell based therapies for EB using autologous induced pluripotent stem cells (iPSCs) derived from

  14. Stem-Cell Based Therapies for Epidermolysis Bullosa

    DTIC Science & Technology

    2014-10-01

    This application addresses the FY11 PRMRP Topic Area, Epidermolysis Bullosa, and proposes to develop stem - cell based therapies for junctional...accomplish this goal, we are proposing to develop stem - cell based therapies for EB using autologous induced pluripotent stem cells (iPSCs) derived from

  15. Representations of stem cell clinics on Twitter.

    PubMed

    Kamenova, Kalina; Reshef, Amir; Caulfield, Timothy

    2014-12-01

    The practice of travelling abroad to receive unproven and unregulated stem cell treatments has become an increasingly problematic global phenomenon known as 'stem cell tourism'. In this paper, we examine representations of nine major clinics and providers of such treatments on the microblogging network Twitter. We collected and conducted a content analysis of Twitter posts (n = 363) by these establishments and by other users mentioning them, focusing specifically on marketing claims about treatment procedures and outcomes, discussions of safety and efficacy of stem cell transplants, and specific representations of patients' experiences. Our analysis has shown that there were explicit claims or suggestions of benefits associated with unproven stem cell treatments in approximately one third of the tweets and that patients' experiences, whenever referenced, were presented as invariably positive and as testimonials about the efficacy of stem cell transplants. Furthermore, the results indicated that the tone of most tweets (60.2 %) was overwhelmingly positive and there were rarely critical discussions about significant health risks associated with unproven stem cell therapies. When placed in the context of past research on the problems associated with the marketing of unproven stem cell therapies, this analysis of representations on Twitter suggests that discussions in social media have also remained largely uncritical of the stem cell tourism phenomenon, with inaccurate representations of risks and benefits for patients.

  16. Epigenetics in cancer stem cells.

    PubMed

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  17. 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

  18. Pluripotent Stem Cells and Gene Therapy

    PubMed Central

    Simara, Pavel; Motl, Jason A.; Kaufman, Dan S.

    2013-01-01

    Human pluripotent stem cells represent an accessible cell source for novel cell-based clinical research and therapies. With the realization of induced pluripotent stem cells (iPSCs), it is possible to produce almost any desired cell type from any patient's cells. Current developments in gene modification methods have opened the possibility for creating genetically corrected human iPSCs for certain genetic diseases that could be used later in autologous transplantation. Promising preclinical studies have demonstrated correction of disease-causing mutations in a number of hematological, neuronal and muscular disorders. This review aims to summarize these recent advances with a focus on iPSC generation techniques, as well as gene modification methods. We will then further discuss some of the main obstacles remaining to be overcome before successful application of human pluripotent stem cell-based therapy arrives in the clinic and what the future of stem cell research may look like. PMID:23353080

  19. 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...

  20. Technology advancement for integrative stem cell analyses.

    PubMed

    Jeong, Yoon; Choi, Jonghoon; Lee, Kwan Hyi

    2014-12-01

    Scientists have endeavored to use stem cells for a variety of applications ranging from basic science research to translational medicine. Population-based characterization of such stem cells, while providing an important foundation to further development, often disregard the heterogeneity inherent among individual constituents within a given population. The population-based analysis and characterization of stem cells and the problems associated with such a blanket approach only underscore the need for the development of new analytical technology. In this article, we review current stem cell analytical technologies, along with the advantages and disadvantages of each, followed by applications of these technologies in the field of stem cells. Furthermore, while recent advances in micro/nano technology have led to a growth in the stem cell analytical field, underlying architectural concepts allow only for a vertical analytical approach, in which different desirable parameters are obtained from multiple individual experiments and there are many technical challenges that limit vertically integrated analytical tools. Therefore, we propose--by introducing a concept of vertical and horizontal approach--that there is the need of adequate methods to the integration of information, such that multiple descriptive parameters from a stem cell can be obtained from a single experiment.

  1. Development of bioengineering system for stem cell proliferation

    NASA Astrophysics Data System (ADS)

    Park, H. S.; Shah, R.; Shah, C.

    2016-08-01

    From last decades, intensive research in the field of stem cells proliferation had been promoted due to the unique property of stem cells to self-renew themselves into multiples and has potential to replicate into an organ or tissues and so it's highly demanding though challenging. Bioreactor, a mechanical device, works as a womb for stem cell proliferation by providing nutritious environment for the proper growth of stem cells. Various factors affecting stem cells growth are the bioreactor mechanism, feeding of continuous nutrients, healthy environment, etc., but it always remains a challenge for controlling biological parameters. The present paper unveils the design of mechanical device commonly known as bioreactor in tissues engineering and biotech field, use for proliferation of stem cells and imparts the proper growing condition for stem cells. This high functional bioreactor provides automation mixing of cell culture and stem cells. This design operates in conjunction with mechanism of reciprocating motion. Compare to commercial bioreactors, this proposed design is more convenient, easy to operate and less maintenance is required as bioreactor culture bag is made of polyethylene which is single use purpose. Development of this bioengineering system will be beneficial for better growth and expansion of stem cell

  2. Stomach development, stem cells and disease

    PubMed Central

    Kim, Tae-Hee; Shivdasani, Ramesh A.

    2016-01-01

    The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms. PMID:26884394

  3. 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.

  4. 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.

  5. Cancer stem cells of the digestive system.

    PubMed

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Age-related Deterioration of Hematopoietic Stem Cells.

    PubMed

    Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

    2008-11-01

    Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

  7. Age-related Deterioration of Hematopoietic Stem Cells

    PubMed Central

    Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

    2008-01-01

    Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail. PMID:24855509

  8. Progeroid syndromes: models for stem cell aging?

    PubMed

    Bellantuono, I; Sanguinetti, G; Keith, W N

    2012-02-01

    Stem cells are responsible for tissue repair and maintenance and it is assumed that changes observed in the stem cell compartment with age underlie the concomitant decline in tissue function. Studies in murine models have highlighted the importance of intrinsic changes occurring in stem cells with age. They have also drawn the attention to other factors, such as changes in the local or systemic environment as the primary cause of stem cell dysfunction. Whilst knowledge in murine models has been advancing rapidly there has been little translation of these data to human aging. This is most likely due to the difficulties of testing the regenerative capacity of human stem cells in vivo and to substantial differences in the aging phenotype within humans. Here we summarize evidence to show how progeroid syndromes, integrated with other models, can be valuable tools in addressing questions about the role of stem cell aging in human degenerative diseases of older age and the molecular pathways involved.

  9. Spermatogonial Stem Cell Niche and Spermatogonial Stem Cell Transplantation in Zebrafish

    PubMed Central

    Nóbrega, Rafael Henrique; Greebe, Caaj Douwe; van de Kant, Henk; Bogerd, Jan; de França, Luiz Renato; Schulz, Rüdiger W.

    2010-01-01

    Background Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis, and reside within a specific microenvironment in the testes called “niche” which regulates stem cell properties, such as, self-renewal, pluripotency, quiescence and their ability to differentiate. Methodology/Principal Findings Here, we introduce zebrafish as a new model for the study of SSCs in vertebrates. Using 5′-bromo-2′-deoxyuridine (BrdU), we identified long term BrdU-retaining germ cells, type A undifferentiated spermatogonia as putative stem cells in zebrafish testes. Similar to rodents, these cells were preferentially located near the interstitium, suggesting that the SSC niche is related to interstitial elements and might be conserved across vertebrates. This localization was also confirmed by analyzing the topographical distribution of type A undifferentiated spermatogonia in normal, vasa::egfp and fli::egfp zebrafish testes. In the latter one, the topographical arrangement suggested that the vasculature is important for the SSC niche, perhaps as a supplier of nutrients, oxygen and/or signaling molecules. We also developed an SSC transplantation technique for both male and female recipients as an assay to evaluate the presence, biological activity, and plasticity of the SSC candidates in zebrafish. Conclusions/Significance We demonstrated donor-derived spermato- and oogenesis in male and female recipients, respectively, indicating the stemness of type A undifferentiated spermatogonia and their plasticity when placed into an environment different from their original niche. Similar to other vertebrates, the transplantation efficiency was low. This might be attributed to the testicular microenvironment created after busulfan depletion in the recipients, which may have caused an imbalance between factors regulating self-renewal or differentiation of the transplanted SSCs. PMID:20862221

  10. Chromatin remodeling and stem cell theory of relativity.

    PubMed

    Cerny, Jan; Quesenberry, Peter J

    2004-10-01

    The field of stem cell biology is currently being redefined. Stem cell (hematopoietic and non-hematopoietic) differentiation has been considered hierarchical in nature, but recent data suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. The stem cell (hematopoietic and non-hematopoietic) phenotype, the total differentiation capacity (hematopoietic and non-hematopoietic), gene expression as well as other stem cell functional characteristics (homing, receptor and adhesion molecule expression) vary throughout a cell-cycle transit widely. This seems to be dependent on shifting chromatin and gene expression with cell-cycle transit. The published data on DNA methylation, histone acetylation, and also RNAi, the major regulators of gene expression, conjoins very well and provides an explanation for the major issues of stem cell biology. Those features of stem cells mentioned above can be rather difficult to apprehend when a classical hierarchy biology view is applied, but they become clear and easier to understand once they are correlated with the underlining epigenetic changes. We are entering a new era of stem cell biology the era of "chromatinomics." We are one step closer to the practical use of cellular therapy for degenerative diseases.

  11. A paired comparison between glioblastoma "stem cells" and differentiated cells.

    PubMed

    Schneider, Matthias; Ströbele, Stephanie; Nonnenmacher, Lisa; Siegelin, Markus D; Tepper, Melanie; Stroh, Sebastien; Hasslacher, Sebastian; Enzenmüller, Stefanie; Strauss, Gudrun; Baumann, Bernd; Karpel-Massler, Georg; Westhoff, Mike-Andrew; Debatin, Klaus-Michael; Halatsch, Marc-Eric

    2016-04-01

    Cancer stem cells (CSC) have been postulated to be responsible for the key features of a malignancy and its maintenances, as well as therapy resistance, while differentiated cells are believed to make up the rapidly growing tumour bulk. It is therefore important to understand the characteristics of those two distinct cell populations in order to devise treatment strategies which effectively target both cohorts, in particular with respect to cancers, such as glioblastoma. Glioblastoma is the most common primary brain tumour in adults, with a mean patient survival of 12-15 months. Importantly, therapeutic improvements have not been forthcoming in the last decade. In this study we compare key features of three pairs of glioblastoma cell populations, each pair consisting of stem cell-like and differentiated cells derived from an individual patient. Our data suggest that while growth rates and expression of key survival- and apoptosis-mediating proteins are more similar according to differentiation status than genetic similarity, we found no intrinsic differences in response to standard therapeutic interventions, namely exposure to radiation or the alkylating agent temozolomide. Interestingly, we could demonstrate that both stem cell-like and differentiated cells possess the ability to form stem cell-containing tumours in immunocompromised mice and that differentiated cells could potentially be dedifferentiated to potential stem cells. Taken together our data suggest that the differences between tumour stem cell and differentiated cell are particular fluent in glioblastoma. © 2015 UICC.

  12. Stem Cell Banking: A Global View.

    PubMed

    Stacey, Glyn

    2017-01-01

    Stem cell banking has been a topic of discussion and debate for more than a decade since the first public services to supply human embryonic stem cells (hESCs) were established in the USA and the UK. This topic has received a recent revival with numerous ambitious programmes announced to deliver large collections of human induced pluripotency cell (hiPSC) lines. This chapter will provide a brief overview charting the development of stem cell banks, their value, and their likely role in the future.

  13. Biomaterials and Stem Cells for Tissue Engineering

    PubMed Central

    Zhang, Zhanpeng; Gupte, Melanie J.; Ma, Peter X.

    2013-01-01

    Importance of the field Organ failure and tissue loss are challenging health issues due to widespread injury, the lack of organs for transplantation, and limitations of conventional artificial implants. The field of tissue engineering aims to provide alternative living substitutes that restore, maintain or improve tissue function. Areas covered in this review In this paper, a wide range of porous scaffolds are reviewed, with an emphasis on phase separation techniques that generate advantageous nanofibrous 3D scaffolds for stem cell-based tissue engineering applications. In addition, methods for presentation and delivery of bioactive molecules to mimic the properties of stem cell niche are summarized. Recent progress in using these bio-instructive scaffolds to support stem cell differentiation and tissue regeneration is also presented. What the reader will gain Stem cells have great clinical potential because of their capability to differentiate into multiple cell types. Biomaterials have served as artificial extracellular environments to regulate stem cell behavior. Biomaterials with various physical, mechanical, and chemical properties can be designed to control stem cell development for regeneration. Take home message The research at the interface of stem cell biology and biomaterials has made and will continue to make exciting advances in tissue engineering. PMID:23327471

  14. Stem cell transplantation (cord blood transplants).

    PubMed

    Chao, Nelson J; Emerson, Stephen G; Weinberg, Kenneth I

    2004-01-01

    Allogeneic stem cell transplantation is an accepted treatment modality for selected malignant and non-malignant diseases. However, the ability to identify suitably matched related or unrelated donors can be difficult in some patients. Alternative sources of stem cells such as cord blood provide a readily available graft for such patients. Data accumulated over the past several years have demonstrated that the use of cord blood is an accepted source of stem cells for pediatric patients. Since the cell numbers of hematopoietic progenitors in cord blood is limited and the collection can occur only in a single occasion, its use in adult patients can be more problematic. Here, new developments in the use of cord blood for adults and studies aimed at expansion of cord blood cells and immune reconstitution are described. In Section I, Dr. Nelson Chao describes the early data in cord blood transplantation in adult patients. The patient outcomes are reviewed and analyzed for various factors such as cell dose, HLA typing, and patient selection that could have contributed to the final outcome of these adult patients. Myeloablative as well as nonmyeloablative approaches are presented. Discussion of the various benefits and risks are presented. More recent data from multiple single institutions as well as larger registry data comparisons are also provided. Analyses of these studies suggest methods to improve on the outcome. These newer data should lead to a logical progression in the use of cord blood cells in adult patients. In Section II, Dr. Stephen Emerson describes the historical efforts associated with expansion of hematopoietic stem cells, specifically with cord blood cells. These efforts to expand cord blood cells continue with novel methods. Moreover, a better understanding of stem cell biology and signaling is critical if we are to be able to effectively expand these cells for clinical use. An alternative, more direct, approach to expanding stem cells could be

  15. 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

  16. Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

    PubMed Central

    Wu, Jincheng; Tzanakakis, Emmanuel S.

    2014-01-01

    Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

  17. 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.

  18. Cell adhesion monitoring of human induced pluripotent stem cell based on intrinsic molecular charges

    NASA Astrophysics Data System (ADS)

    Sugimoto, Haruyo; Sakata, Toshiya

    2014-01-01

    We have shown a simple way for real-time, quantitative, non-invasive, and non-label monitoring of human induced pluripotent stem (iPS) cell adhesion by use of a biologically coupled-gate field effect transistor (bio-FET), which is based on detection of molecular charges at cell membrane. The electrical behavior revealed quantitatively the electrical contacts of integrin-receptor at the cell membrane with RGDS peptide immobilized at the gate sensing surface, because that binding site was based on cationic α chain of integrin. The platform based on the bio-FET would provide substantial information to evaluate cell/material bio-interface and elucidate biding mechanism of adhesion molecules, which could not be interpreted by microscopic observation.

  19. 3D modeling of cancer stem cell niche

    PubMed Central

    He, Jun; Xiong, Li; Li, Qinglong; Lin, Liangwu; Miao, Xiongying; Yan, Shichao; Hong, Zhangyong; Yang, Leping; Wen, Yu; Deng, Xiyun

    2018-01-01

    Cancer stem cells reside in a distinct microenvironment called niche. The reciprocal interactions between cancer stem cells and niche contribute to the maintenance and enrichment of cancer stem cells. In order to simulate the interactions between cancer stem cells and niche, three-dimensional models have been developed. These in vitro culture systems recapitulate the spatial dimension, cellular heterogeneity, and the molecular networks of the tumor microenvironment and show great promise in elucidating the pathophysiology of cancer stem cells and designing more clinically relavant treatment modalites. PMID:29416698

  20. Stem cells for the treatment of neurodegenerative diseases

    PubMed Central

    2010-01-01

    Stem cells offer an enormous pool of resources for the understanding of the human body. One proposed use of stem cells has been as an autologous therapy. The use of stem cells for neurodegenerative diseases has become of interest. Clinical applications of stem cells for Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis will increase in the coming years, and although great care will need to be taken when moving forward with prospective treatments, the application of stem cells is highly promising. PMID:21144012

  1. Stem cell bioprocessing: fundamentals and principles

    PubMed Central

    Placzek, Mark R.; Chung, I-Ming; Macedo, Hugo M.; Ismail, Siti; Mortera Blanco, Teresa; Lim, Mayasari; Min Cha, Jae; Fauzi, Iliana; Kang, Yunyi; Yeo, David C.L.; Yip Joan Ma, Chi; Polak, Julia M.; Panoskaltsis, Nicki; Mantalaris, Athanasios

    2008-01-01

    In recent years, the potential of stem cell research for tissue engineering-based therapies and regenerative medicine clinical applications has become well established. In 2006, Chung pioneered the first entire organ transplant using adult stem cells and a scaffold for clinical evaluation. With this a new milestone was achieved, with seven patients with myelomeningocele receiving stem cell-derived bladder transplants resulting in substantial improvements in their quality of life. While a bladder is a relatively simple organ, the breakthrough highlights the incredible benefits that can be gained from the cross-disciplinary nature of tissue engineering and regenerative medicine (TERM) that encompasses stem cell research and stem cell bioprocessing. Unquestionably, the development of bioprocess technologies for the transfer of the current laboratory-based practice of stem cell tissue culture to the clinic as therapeutics necessitates the application of engineering principles and practices to achieve control, reproducibility, automation, validation and safety of the process and the product. The successful translation will require contributions from fundamental research (from developmental biology to the ‘omics’ technologies and advances in immunology) and from existing industrial practice (biologics), especially on automation, quality assurance and regulation. The timely development, integration and execution of various components will be critical—failures of the past (such as in the commercialization of skin equivalents) on marketing, pricing, production and advertising should not be repeated. This review aims to address the principles required for successful stem cell bioprocessing so that they can be applied deftly to clinical applications. PMID:19033137

  2. Manifestations and mechanisms of stem cell aging

    PubMed Central

    Liu, Ling

    2011-01-01

    Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell–based therapy of age-related diseases. PMID:21502357

  3. Generation of functional organs from stem cells.

    PubMed

    Liu, Yunying; Yang, Ru; He, Zuping; Gao, Wei-Qiang

    2013-01-01

    We are now well entering the exciting era of stem cells. Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, diabetes, and etc. It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue. In fact, organ transplantation has been successfully practiced in clinics for liver or kidney failure. However, the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs. Toward that direction, generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists. Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells, a blastocyst complementation system, tissue decellularization/recellularization and a combination of stem cells and tissue engineering.

  4. Stem Cells, Science, and Public Reasoning

    ERIC Educational Resources Information Center

    Hurlbut, J. Benjamin; Robert, Jason Scott

    2012-01-01

    These are interesting days in the scientific, social, and political debates about human embryonic stem cell research. Pluripotent stem cells--cells that can, in principle, give rise to the body's full range of cell types--were previously derivable only from human embryos that were destroyed in the process. Now, a variety of somatic cell types can…

  5. Variability of human pluripotent stem cell lines.

    PubMed

    Ortmann, Daniel; Vallier, Ludovic

    2017-10-01

    Human pluripotent stem cells derived from embryos (human Embryonic Stem Cells or hESCs) or generated by direct reprogramming of somatic cells (human Induced Pluripotent Stem Cells or hiPSCs) can proliferate almost indefinitely in vitro while maintaining the capacity to differentiate into a broad diversity of cell types. These two properties (self-renewal and pluripotency) confers human pluripotent stem cells a unique interest for clinical applications since they could allow the production of infinite quantities of cells for disease modelling, drug screening and cell based therapy. However, recent studies have clearly established that human pluripotent stem cell lines can display variable capacity to differentiate into specific lineages. Consequently, the development of universal protocols of differentiation which could work efficiently with any human pluripotent cell line is complicated substantially. As a consequence, each protocol needs to be adapted to every cell line thereby limiting large scale applications and precluding personalised therapies. Here, we summarise our knowledge concerning the origin of this variability and describe potential solutions currently available to bypass this major challenge. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Evolution of Energy Metabolism, Stem Cells and Cancer Stem Cells: How the Warburg and Barker Hypotheses Might Be Linked

    PubMed Central

    Trosko, James E.; Kang, Kyung-Sun

    2012-01-01

    The evolutionary transition from single cells to the metazoan forced the appearance of adult stem cells and a hypoxic niche, when oxygenation of the environment forced the appearance of oxidative phosphorylation from that of glycolysis. The prevailing paradigm in the cancer field is that cancers start from the “immortalization” or “re-programming” of a normal, differentiated cell with many mitochondria, that metabolize via oxidative phosphorylation. This paradigm has been challenged with one that assumes that the target cell for carcinogenesis is the normal, immortal adult stem cell, with few mitochondria. This adult organ-specific stem cell is blocked from “mortalizing” or from “programming” to be terminally differentiated. Two hypotheses have been offered to explain cancers, namely, the “stem cell theory” and the “de-differentiation” or “re-programming” theory. This Commentary postulates that the paleochemistry of the oceans, which, initially, provided conditions for life’ s energy to arise via glycolysis, changed to oxidative phosphorylation for life’ s processes. In doing so, stem cells evolved, within hypoxic niches, to protect the species germinal and somatic genomes. This Commentary provides support for the “stem cell theory”, in that cancer cells, which, unlike differentiated cells, have few mitochondria and metabolize via glycolysis. The major argument against the “de-differentiation theory” is that, if re-programming of a differentiated cell to an “induced pluri-potent stem cell” happened in an adult, teratomas, rather than carcinomas, should be the result. PMID:24298354

  7. Craniofacial Tissue Engineering by Stem Cells

    PubMed Central

    Mao, J.J.; Giannobile, W.V.; Helms, J.A.; Hollister, S.J.; Krebsbach, P.H.; Longaker, M.T.; Shi, S.

    2008-01-01

    Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures—such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue—have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss. PMID:17062735

  8. 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.

  9. Nanotechnology in stem cells research: advances and applications.

    PubMed

    Deb, Kaushik Dilip; Griffith, May; Muinck, Ebo De; Rafat, Mehrdad

    2012-01-01

    Human beings suffer from a myriad of disorders caused by biochemical or biophysical alteration of physiological systems leading to organ failure. For a number of these conditions, stem cells and their enormous reparative potential may be the last hope for restoring function to these failing organ or tissue systems. To harness the potential of stem cells for biotherapeutic applications, we need to work at the size scale of molecules and processes that govern stem cells fate. Nanotechnology provides us with such capacity. Therefore, effective amalgamation of nanotechnology and stem cells - medical nanoscience or nanomedicine - offers immense benefits to the human race. The aim of this paper is to discuss the role and importance of nanotechnology in stem cell research by focusing on several important areas such as stem cell visualization and imaging, genetic modifications and reprogramming by gene delivery systems, creating stem cell niche, and similar therapeutic applications.

  10. 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.

  11. Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

    PubMed

    Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

    2018-02-27

    Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

  12. EMPOWERING ADULT STEM CELLS FOR MYOCARDIAL REGENERATION

    PubMed Central

    Mohsin, Sadia; Siddiqi, Sailay; Collins, Brett; Sussman, Mark A.

    2012-01-01

    Treatment strategies for heart failure remain a high priority for ongoing research due to the profound unmet need in clinical disease coupled with lack of significant translational progress. The underlying issue is the same whether the cause is acute damage, chronic stress from disease, or aging: progressive loss of functional cardiomyocytes and diminished hemodynamic output. To stave off cardiomyocyte losses, a number of strategic approaches have been embraced in recent years involving both molecular and cellular approaches to augment myocardial structure and performance. Resultant excitement surrounding regenerative medicine in the heart has been tempered by realizations that reparative processes in the heart are insufficient to restore damaged myocardium to normal functional capacity and that cellular cardiomyoplasty is hampered by poor survival, proliferation, engraftment and differentiation of the donated population. To overcome these limitations, a combination of molecular and cellular approaches needs to be adopted involving use of genetic engineering to enhance resistance to cell death and increase regenerative capacity. This review will highlight biological properties of approached to potentiate stem cell-mediated regeneration to promote enhanced myocardial regeneration, persistence of donated cells, and long lasting tissue repair. Optimizing cell delivery and harnessing the power of survival signaling cascades for ex vivo genetic modification of stem cells prior to reintroduction into the patient will be critical to enhance the efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based therapy has great promise for treatment of heart failure to combat the loss of cardiac structure and function associated with acute damage, chronic disease or aging. PMID:22158649

  13. Müller stem cell dependent retinal regeneration.

    PubMed

    Chohan, Annu; Singh, Usha; Kumar, Atul; Kaur, Jasbir

    2017-01-01

    Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas. Here, we review the current status of retinal regeneration of the human eye by Müller stem cells. This review elucidates the current status of retinal regeneration by Müller stem cells, along with major retinal degenerative diseases where these stem cells play regenerative role in retinal repair and replacement. Copyright © 2016. Published by Elsevier B.V.

  14. Advances in reprogramming somatic cells to induced pluripotent stem cells.

    PubMed

    Patel, Minal; Yang, Shuying

    2010-09-01

    Traditionally, nuclear reprogramming of cells has been performed by transferring somatic cell nuclei into oocytes, by combining somatic and pluripotent cells together through cell fusion and through genetic integration of factors through somatic cell chromatin. All of these techniques changes gene expression which further leads to a change in cell fate. Here we discuss recent advances in generating induced pluripotent stem cells, different reprogramming methods and clinical applications of iPS cells. Viral vectors have been used to transfer transcription factors (Oct4, Sox2, c-myc, Klf4, and nanog) to induce reprogramming of mouse fibroblasts, neural stem cells, neural progenitor cells, keratinocytes, B lymphocytes and meningeal membrane cells towards pluripotency. Human fibroblasts, neural cells, blood and keratinocytes have also been reprogrammed towards pluripotency. In this review we have discussed the use of viral vectors for reprogramming both animal and human stem cells. Currently, many studies are also involved in finding alternatives to using viral vectors carrying transcription factors for reprogramming cells. These include using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. Applications of these techniques have been discussed in detail including its advantages and disadvantages. Finally, current clinical applications of induced pluripotent stem cells and its limitations have also been reviewed. Thus, this review is a summary of current research advances in reprogramming cells into induced pluripotent stem cells.

  15. Concise Review: Stem Cells in Osteoimmunology.

    PubMed

    Fierro, Fernando A; Nolta, Jan A; Adamopoulos, Iannis E

    2017-06-01

    Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent. Latest advances in the area of stem cell biology have enabled us to gain a better understanding of how these differentiation processes occur in physiological and pathological conditions. In this review we postulate that modulation of stem cells during inflammatory conditions is a necessary prerequisite of bone remodeling and therefore an essential new component to the field of osteoimmunology. In this context, we highlight the role of transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1), because it directly links inflammation with differentiation of osteoclasts and osteoblasts. Stem Cells 2017;35:1461-1467. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  16. Bioreactor Engineering of Stem Cell Environments

    PubMed Central

    Tandon, Nina; Marolt, Darja; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2013-01-01

    Stem cells hold promise to revolutionize modern medicine by development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to translation of stem cell based therapies into the clinic. PMID:23531529

  17. Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells.

    PubMed

    Hamano, Sayuri; Tomokiyo, Atsushi; Hasegawa, Daigaku; Yoshida, Shinichiro; Sugii, Hideki; Mitarai, Hiromi; Fujino, Shoko; Wada, Naohisa; Maeda, Hidefumi

    2018-01-15

    The periodontal ligament (PDL) plays an important role in anchoring teeth in the bone socket. Damage to the PDL, such as after severe inflammation, can be treated with a therapeutic strategy that uses stem cells derived from PDL tissue (PDLSCs), a strategy that has received intense scrutiny over the past decade. However, there is an insufficient number of PDLSCs within the PDL for treating such damage. Therefore, we sought to induce the differentiation of induced pluripotent stem (iPS) cells into PDLSCs as an initial step toward PDL therapy. To this end, we first induced iPS cells into neural crest (NC)-like cells. We then captured the p75 neurotrophic receptor-positive cells (iPS-NC cells) and cultured them on an extracellular matrix (ECM) produced by human PDL cells (iPS-NC-PDL cells). These iPS-NC-PDL cells showed reduced expression of embryonic stem cell and NC cell markers as compared with iPS and iPS-NC cells, and enrichment of mesenchymal stem cell markers. The cells also had a higher proliferative capacity, multipotency, and elevated expression of PDL-related markers than iPS-NC cells cultured on fibronectin and laminin (iPS-NC-FL cells) or ECM produced by human skin fibroblast cells (iPS-NC-SF cells). Overall, we present a culture method to produce high number of PDLSC-like cells from iPS cells as a first step toward a strategy for PDL regeneration.

  18. Stomach development, stem cells and disease.

    PubMed

    Kim, Tae-Hee; Shivdasani, Ramesh A

    2016-02-15

    The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms. © 2016. Published by The Company of Biologists Ltd.

  19. Stem cell-based biological tooth repair and regeneration

    PubMed Central

    Volponi, Ana Angelova; Pang, Yvonne; Sharpe, Paul T.

    2010-01-01

    Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease. PMID:21035344

  20. Proinflammatory Stem Cell Signaling in Cardiac Ischemia

    PubMed Central

    Herrmann, Jeremy L.; Markel, Troy A.; Abarbanell, Aaron M.; Weil, Brent R.; Wang, Meijing; Wang, Yue; Tan, Jiangning

    2009-01-01

    Abstract Cardiovascular disease remains a leading cause of mortality in developed nations, despite continued advancement in modern therapy. Progenitor and stem cell–based therapy is a novel treatment for cardiovascular disease, and modest benefits in cardiac recovery have been achieved in small clinical trials. This therapeutic modality remains challenged by limitations of low donor-cell survival rates, transient recovery of cardiac function, and the technical difficulty of applying directed cell therapy. Understanding the signaling mechanisms involved in the stem cell response to ischemia has revealed opportunities to modify directly aspects of these pathways to improve their cardioprotective abilities. This review highlights general considerations of stem cell therapy for cardiac disease, reviews the major proinflammatory signaling pathways of mesenchymal stem cells, and reviews ex vivo modifications of stem cells based on these pathways. Antioxid. Redox Signal. 11, 1883–1896. PMID:19187005

  1. Hardwiring stem cell communication through tissue structure

    PubMed Central

    Xin, Tianchi; Greco, Valentina; Myung, Peggy

    2016-01-01

    Adult stem cells across diverse organs self-renew and differentiate to maintain tissue homeostasis. How stem cells receive input to preserve tissue structure and function largely relies on their communication with surrounding cellular and non-cellular elements. As such, how tissues are organized and patterned not only reflects organ function but also inherently hardwires networks of communication between stem cells and their environment to direct tissue homeostasis and injury repair. This review highlights how different methods of stem cell communication reflect the unique organization and function of diverse tissues. PMID:26967287

  2. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma.

    PubMed

    Mark, Tomer; Stern, Jessica; Furst, Jessica R; Jayabalan, David; Zafar, Faiza; LaRow, April; Pearse, Roger N; Harpel, John; Shore, Tsiporah; Schuster, Michael W; Leonard, John P; Christos, Paul J; Coleman, Morton; Niesvizky, Ruben

    2008-07-01

    A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte-colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobilization at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy plus G-CSF, versus 33% mobilized with G-CSF alone (P < .0001). The duration of prior lenalidomide therapy did not correlate with success of stem cell harvests (P = .91). In conclusion, Cy can be added to G-CSF for stem cell mobilization to successfully overcome the suppressive effect of prior treatment with lenalidomide.

  3. Stem Cell Mobilization with Cyclophosphamide Overcomes the Suppressive Effect of Lenalidomide Therapy on Stem Cell Collection in Multiple Myeloma

    PubMed Central

    Mark, Tomer; Stern, Jessica; Furst, Jessica R.; Jayabalan, David; Zafar, Faiza; LaRow, April; Pearse, Roger N.; Harpel, John; Shore, Tsiporah; Schuster, Michael W.; Leonard, John P.; Christos, Paul J.; Coleman, Morton; Niesvizky, Ruben

    2013-01-01

    A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte- colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobilization at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy plus G-CSF, versus 33% mobilized with G-CSF alone (P<.0001). The duration of prior lenalidomide therapy did not correlate with success of stem cell harvests (P = .91). In conclusion, Cy can be added to G-CSF for stem cell mobilization to successfully overcome the suppressive effect of prior treatment with lenalidomide. PMID:18541199

  4. [A comparative study on inducing non-homologous mesenchymal stem cells to differentiate into neural stem cells using non-homologous cerebrospinal fluid].

    PubMed

    Ren, Chao; Liu, Xiaoyun; Wan, Meirong; Geng, Deqin; Ge, Wei; Li, Jinmei; Zhang, Weiwei

    2013-12-01

    In order to set up a base for stem cells to be widely used in clinical medicine, we tried to optimize, in this study, the technique that induces human mesenchymal stem cells (hMSCs) to differentiate into neural stem cells by using cerebrospinal fluid (CSF) from the different groups. After the induction, presence of neural stem cells was confirmed with microscope observation, flow cytometry analysis, immunohistochemistry and fluorescent immunohistochemistry. At the same time, we also compared and analysed the data of the number of stem cells when it totally met the requirements for clinical treatment and the days required. At last, we confirmed that hMSCs could be induced to differentiate into neural stem cells, and that the number of cells totally met the requirements for clinical treatment. But there were some differences both in the number of cells and the days required. Among the groups, the group that marrow mesenchymal stem cells from patients own induced by CSF from healthy volunteers used the shortest time and the quantity of the cells was significantly higher than those of the others.

  5. 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.

  6. Technology Advancement for Integrative Stem Cell Analyses

    PubMed Central

    Jeong, Yoon

    2014-01-01

    Scientists have endeavored to use stem cells for a variety of applications ranging from basic science research to translational medicine. Population-based characterization of such stem cells, while providing an important foundation to further development, often disregard the heterogeneity inherent among individual constituents within a given population. The population-based analysis and characterization of stem cells and the problems associated with such a blanket approach only underscore the need for the development of new analytical technology. In this article, we review current stem cell analytical technologies, along with the advantages and disadvantages of each, followed by applications of these technologies in the field of stem cells. Furthermore, while recent advances in micro/nano technology have led to a growth in the stem cell analytical field, underlying architectural concepts allow only for a vertical analytical approach, in which different desirable parameters are obtained from multiple individual experiments and there are many technical challenges that limit vertically integrated analytical tools. Therefore, we propose—by introducing a concept of vertical and horizontal approach—that there is the need of adequate methods to the integration of information, such that multiple descriptive parameters from a stem cell can be obtained from a single experiment. PMID:24874188

  7. 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

  8. Modulating the stem cell niche for tissue regeneration

    PubMed Central

    Lane, Steven W; Williams, David A; Watt, Fiona M

    2015-01-01

    The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell–extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell–niche interactions. PMID:25093887

  9. PLURIPOTENT STEM CELL APPLICATIONS FOR REGENERATIVE MEDICINE

    PubMed Central

    Angelos, Mathew G.; Kaufman, Dan S.

    2015-01-01

    Purpose of Review In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We also discuss combined cell and gene therapy via correction of defined mutations in human pluripotent stem cells and provide commentary on key obstacles facing wide-scale clinical adoption of pluripotent stem cell-based therapy. Recent Findings Initial data suggest hESC/hiPSC-derived cell products used for retinal repair and spinal cord injury are safe for human use. Early stage studies for treatment of cardiac injury and diabetes are also in progress. However, there remain key concerns regarding the safety and efficacy of these cells that need to be addressed in additional well-designed clinical trials. Advances using the CRISPR/Cas9 gene-editing system offer an improved tool for more rapid and on-target gene correction of genetic diseases. Combined gene and cell therapy using human pluripotent stem cells may provide an additional curative approach for disabling or lethal genetic and degenerative diseases where there are currently limited therapeutic opportunities. Summary Human pluripotent stem cells are emerging as a promising tool to produce cells and tissues suitable for regenerative therapy for a variety of genetic and degenerative diseases. PMID:26536430

  10. Satellite Cells and the Muscle Stem Cell Niche

    PubMed Central

    Yin, Hang; Price, Feodor

    2013-01-01

    Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905

  11. Isolation and morphology of Stem Cells from Deciduous Tooth (SHED) and Human Dental Pulp Stem Cells (hDPSC)

    NASA Astrophysics Data System (ADS)

    Ariffin, Shahrul Hisham Zainal; Manogaran, Thanaletchumi; Abidin, Intan Zarina Zainol; Senafi, Sahidan; Wahab, Rohaya Megat Abdul

    2016-11-01

    Dental pulp is a tissue obtained from pulp chamber of deciduous and permanent tooth which contain stem cells. Stem cell isolation procedure is performed to obtain cells from tissue using enzymatic digestion. The aim of this study is to isolate and observe the morphology of stem cells during passage 0 and passage 3. Dental pulp from deciduous and permanent tooth was enzymatically digested using collagenase Type I and cells obtained were cultured in DMEM-KO that contains 10% fetal bovine serum, 1% antibiotic-antimycotic solution and 0.001× GlutaMax®. During culture, cell morphology was observed under the microscope on day 3, 16 and 33 and captured using cellB software. Giemsa staining was conducted on cells at passage 3. Cells attached at the bottom of the flask on day 3 and started forming small colonies. Cells became confluent after approximately 4 weeks. Both Stem Cells from Deciduous Tooth (SHED) and Human Dental Pulp Stem Cells (hDPSC) exhibited fibroblast-like morphology during passage 0 and passage 3. Meanwhile, Giemsa staining at passage 3 revealed single intact nucleus surrounded by fibroblastic cytoplasm structure. It can be concluded that SHED and hDPSC showed consistent fibroblast-like morphology throughout culture period.

  12. The retinoblastoma tumor suppressor and stem cell biology.

    PubMed

    Sage, Julien

    2012-07-01

    Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. A better understanding of stem cell biology, including embryonic and adult stem cells, will allow the scientific community to better comprehend a number of pathologies and possibly design novel approaches to treat patients with a variety of diseases. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In some contexts, loss of RB function in stem or progenitor cells is a key event in the initiation of cancer and determines the subtype of cancer arising from these pluripotent cells by altering their fate. In other cases, RB inactivation is often not sufficient to initiate cancer but may still lead to some stem cell expansion, raising the possibility that strategies aimed at transiently inactivating RB might provide a novel way to expand functional stem cell populations. Future experiments dedicated to better understanding how RB and the RB pathway control a stem cell's decisions to divide, self-renew, or give rise to differentiated progeny may eventually increase our capacity to control these decisions to enhance regeneration or help prevent cancer development.

  13. Asymmetric cell division of stem cells in the lung and other systems

    PubMed Central

    Berika, Mohamed; Elgayyar, Marwa E.; El-Hashash, Ahmed H. K.

    2014-01-01

    New insights have been added to identification, behavior and cellular properties of embryonic and tissue-specific stem cells over the last few years. The modes of stem cell division, asymmetric vs. symmetric, are tightly regulated during development and regeneration. The proper choice of a stem cell to divide asymmetrically or symmetrically has great consequences for development and disease because inappropriate asymmetric division disrupts organ morphogenesis, whereas uncontrolled symmetric division induces tumorigenesis. Therefore, understanding the behavior of lung stem cells could identify innovative solutions for restoring normal morphogenesis and/or regeneration of different organs. In this concise review, we describe recent studies in our laboratory about the mode of division of lung epithelial stem cells. We also compare asymmetric cell division (ACD) in the lung stem cells with other tissues in different organisms. PMID:25364740

  14. Intestinal stem cells in the adult Drosophila midgut

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

    Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu; Edgar, Bruce A., E-mail: b.edgar@dkfz.de; Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights:more » Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.« less

  15. Stem cells in clinical practice: applications and warnings.

    PubMed

    Lodi, Daniele; Iannitti, Tommaso; Palmieri, Beniamino

    2011-01-17

    Stem cells are a relevant source of information about cellular differentiation, molecular processes and tissue homeostasis, but also one of the most putative biological tools to treat degenerative diseases. This review focuses on human stem cells clinical and experimental applications. Our aim is to take a correct view of the available stem cell subtypes and their rational use in the medical area, with a specific focus on their therapeutic benefits and side effects. We have reviewed the main clinical trials dividing them basing on their clinical applications, and taking into account the ethical issue associated with the stem cell therapy. We have searched Pubmed/Medline for clinical trials, involving the use of human stem cells, using the key words "stem cells" combined with the key words "transplantation", "pathology", "guidelines", "properties" and "risks". All the relevant clinical trials have been included. The results have been divided into different categories, basing on the way stem cells have been employed in different pathological conditions.

  16. Coculturing with endothelial cells promotes in vitro maturation and electrical coupling of human embryonic stem cell-derived cardiomyocytes.

    PubMed

    Pasquier, Jennifer; Gupta, Renuka; Rioult, Damien; Hoarau-Véchot, Jessica; Courjaret, Raphael; Machaca, Khaled; Al Suwaidi, Jassim; Stanley, Edouard G; Rafii, Shahin; Elliott, David A; Abi Khalil, Charbel; Rafii, Arash

    2017-06-01

    Pluripotent human embryonic stem cells (hESC) are a promising source of repopulating cardiomyocytes. We hypothesized that we could improve maturation of cardiomyocytes and facilitate electrical interconnections by creating a model that more closely resembles heart tissue; that is, containing both endothelial cells (ECs) and cardiomyocytes. We induced cardiomyocyte differentiation in the coculture of an hESC line expressing the cardiac reporter NKX2.5-green fluorescent protein (GFP), and an Akt-activated EC line (E4 + ECs). We quantified spontaneous beating rates, synchrony, and coordination between different cardiomyocyte clusters using confocal imaging of Fura Red-detected calcium transients and computer-assisted image analysis. After 8 days in culture, 94% ± 6% of the NKX2-5GFP + cells were beating when hESCs embryonic bodies were plated on E4 + ECs compared with 34% ± 12.9% for controls consisting of hESCs cultured on BD Matrigel (BD Biosciences) without ECs at Day 11 in culture. The spatial organization of beating areas in cocultures was different. The GFP + cardiomyocytes were close to the E4 + ECs. The average beats/min of the cardiomyocytes in coculture was faster and closer to physiologic heart rates compared with controls (50 ± 14 [n = 13] vs 25 ± 9 [n = 8]; p < 0.05). The coculture with ECs led to synchronized beating relying on the endothelial network, as illustrated by the loss of synchronization upon the disruption of endothelial bridges. The coculturing of differentiating cardiomyocytes with Akt-activated ECs but not EC-conditioned media results in (1) improved efficiency of the cardiomyocyte differentiation protocol and (2) increased maturity leading to better intercellular coupling with improved chronotropy and synchrony. Copyright © 2017. Published by Elsevier Inc.

  17. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    PubMed

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  18. The epithelial-mesenchymal transition generates cells with properties of stem cells.

    PubMed

    Mani, Sendurai A; Guo, Wenjun; Liao, Mai-Jing; Eaton, Elinor Ng; Ayyanan, Ayyakkannu; Zhou, Alicia Y; Brooks, Mary; Reinhard, Ferenc; Zhang, Cheng Cheng; Shipitsin, Michail; Campbell, Lauren L; Polyak, Kornelia; Brisken, Cathrin; Yang, Jing; Weinberg, Robert A

    2008-05-16

    The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.

  19. On the Stem Cell Origin of Cancer

    PubMed Central

    Sell, Stewart

    2010-01-01

    In each major theory of the origin of cancer—field theory, chemical carcinogenesis, infection, mutation, or epigenetic change—the tissue stem cell is involved in the generation of cancer. Although the cancer type is identified by the more highly differentiated cells in the cancer cell lineage or hierarchy (transit-amplifying cells), the property of malignancy and the molecular lesion of the cancer exist in the cancer stem cell. In the case of teratocarcinomas, normal germinal stem cells have the potential to become cancers if placed in an environment that allows expression of the cancer phenotype (field theory). In cancers due to chemically induced mutations, viral infections, somatic and inherited mutations, or epigenetic changes, the molecular lesion or infection usually first occurs in the tissue stem cells. Cancer stem cells then give rise to transit-amplifying cells and terminally differentiated cells, similar to what happens in normal tissue renewal. However, the major difference between cancer growth and normal tissue renewal is that whereas normal transit amplifying cells usually differentiate and die, at various levels of differentiation, the cancer transit-amplifying cells fail to differentiate normally and instead accumulate (ie, they undergo maturation arrest), resulting in cancer growth. PMID:20431026

  20. 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.

  1. Induced pluripotent stem cells: advances to applications

    PubMed Central

    Nelson, Timothy J; Martinez-Fernandez, Almudena; Yamada, Satsuki; Ikeda, Yasuhiro; Perez-Terzic, Carmen; Terzic, Andre

    2010-01-01

    Induced pluripotent stem cell (iPS) technology has enriched the armamentarium of regenerative medicine by introducing autologous pluripotent progenitor pools bioengineered from ordinary somatic tissue. Through nuclear reprogramming, patient-specific iPS cells have been derived and validated. Optimizing iPS-based methodology will ensure robust applications across discovery science, offering opportunities for the development of personalized diagnostics and targeted therapeutics. Here, we highlight the process of nuclear reprogramming of somatic tissues that, when forced to ectopically express stemness factors, are converted into bona fide pluripotent stem cells. Bioengineered stem cells acquire the genuine ability to generate replacement tissues for a wide-spectrum of diseased conditions, and have so far demonstrated therapeutic benefit upon transplantation in model systems of sickle cell anemia, Parkinson’s disease, hemophilia A, and ischemic heart disease. The field of regenerative medicine is therefore primed to adopt and incorporate iPS cell-based advancements as a next generation stem cell platforms. PMID:21165156

  2. How Stem Cells Speak with Host Immune Cells in Inflammatory Brain Diseases

    PubMed Central

    Pluchino, Stefano; Cossetti, Chiara

    2014-01-01

    Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases. PMID:23633288

  3. 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.

  4. Governing stem cell banks and registries: emerging issues.

    PubMed

    Isasi, Rosario M; Knoppers, Bartha M

    2009-01-01

    The expansion of national and international research efforts in stem cell research is increasingly paired with the trend of establishing stem cell banks and registries. In jurisdictions crossing the spectrum of restrictive to liberal stem cell policies, banks and registries are emerging as an essential resource for transnational access to quality-controlled and ethically sourced stem cell lines. In this study, we report the preliminary findings of a survey of stem cell banks participating in the International Stem Cell Forum's International Stem Cell Banking Initiative (ISCBI). The questionnaire circulated to all ISCBI members addressed both general issues surrounding research policies (e.g., national policies regulating the permissibility of conducting embryonic stem cell research (hESCR)) and, more specifically, issues relating to the governance of stem cell banking projects. The results of the questionnaire were complemented by scholarly research conducted by the authors. This article provides an overview of the current international hESC banking landscape (I). For this purpose, the policy and governance approaches adopted in the surveyed stem cell banks at the national level will be analyzed and areas of convergence and variance will be identified (II). It is beyond the scope of this paper to provide a comprehensive analysis of the wide range of possible governance approaches, policy responses, and their implications. However, we want to provide a starting point for discussion surrounding key questions and challenges as concerns provenance, access, and deposit of hESC lines (III). Finally, while our analysis is focused on research grade hESCs, the lessons to be gleaned from this examination will encourage further thought, analysis, and research into the issues raised in the banking and governance of other sources of stem cell lines (e.g., SCNT, parthenogenesis, iPs) (IV).

  5. 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.

  6. Stem cell sources for regenerative medicine.

    PubMed

    Riazi, Ali M; Kwon, Sarah Y; Stanford, William L

    2009-01-01

    Tissue-resident stem cells or primitive progenitors play an integral role in homeostasis of most organ systems. Recent developments in methodologies to isolate and culture embryonic and somatic stem cells have many new applications poised for clinical and preclinical trials, which will enable the potential of regenerative medicine to be realized. Here, we overview the current progress in therapeutic applications of various stem cells and discuss technical and social hurdles that must be overcome for their potential to be realized.

  7. Advances in translational inner ear stem cell research.

    PubMed

    Warnecke, Athanasia; Mellott, Adam J; Römer, Ariane; Lenarz, Thomas; Staecker, Hinrich

    2017-09-01

    Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types. Potential advantages of mesenchymal/adult stem cells are that they have no ethical constraints on their use. However, appropriate regulatory oversight seems necessary in order to protect patients from side effects. Disadvantages may be the lack of efficacy in many preclinical studies. But if proven safe and efficacious, they are easily translatable to clinical trials. The current review will focus on the potential application on mesenchymal stem cells for the treatment of inner ear disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Stem Cell Research: Unlocking the Mystery of Disease

    MedlinePlus

    ... Issue Past Issues From the Director: Stem Cell Research: Unlocking the Mystery of Disease Past Issues / Summer ... Director, described the need for expanding stem cell research. Recently, he spoke about stem cell research with ...

  9. Applications of stem cell biology to oculoplastic surgery

    PubMed Central

    Daniel, Michael G.; Wu, Albert Y.

    2016-01-01

    Purpose of review This review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery. Recent findings The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte derived stem cells (ADSCs) offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery. Summary The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells (iPSCs) opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through iPSC differentiation, permitting their use in transplants for oculoplastic surgery. PMID:27206262

  10. FDA Warns About Stem Cell Therapies

    MedlinePlus

    ... For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

  11. 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.

  12. Chemokine Receptor Signatures in Allogeneic Stem Cell Transplantation

    DTIC Science & Technology

    2015-08-01

    T - cells in allogeneic hematopoietic stem - cell transplant (HSCT) recipients and identify the role of chemokine receptors in...immune responses after allogeneic hematopoietic stem - cell transplantation (HSCT) in humans. Control of donor T - cells recruitment into target organs...effector T - cells after allogeneic stem - cell transplantation (Aim 1). To characterize the clonal diversity that correlates with

  13. 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.

  14. Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting.

    PubMed

    Liu, Ling; Cheung, Tom H; Charville, Gregory W; Rando, Thomas A

    2015-10-01

    The prospective isolation of purified stem cell populations has dramatically altered the field of stem cell biology, and it has been a major focus of research across tissues in different organisms. Muscle stem cells (MuSCs) are now among the most intensely studied stem cell populations in mammalian systems, and the prospective isolation of these cells has allowed cellular and molecular characterizations that were not dreamed of a decade ago. In this protocol, we describe how to isolate MuSCs from limb muscles of adult mice by fluorescence-activated cell sorting (FACS). We provide a detailed description of the physical and enzymatic dissociation of mononucleated cells from limb muscles, a procedure that is essential in order to maximize cell yield. We also describe a FACS-based method that is used subsequently to obtain highly pure populations of either quiescent or activated MuSCs (VCAM(+)CD31(-)CD45(-)Sca1(-)). The isolation process takes ∼5-6 h to complete. The protocol also allows for the isolation of endothelial cells, hematopoietic cells and mesenchymal stem cells from muscle tissue.

  15. Stem cells in bone diseases: current clinical practice.

    PubMed

    Beyth, Shaul; Schroeder, Josh; Liebergall, Meir

    2011-01-01

    Bone is an obvious candidate tissue for stem cell therapy. This review provides an update of existing stem cell-based clinical treatments for bone pathologies. A systematic computerized literature search was conducted. The following databases were accessed on 10 February 2011: NIH clinical trials database, PubMed, Ovid and Cochrane Reviews. Stem cell therapy offers new options for bone conditions, both acquired and inherited. There is still no agreement on the exact definition of 'mesenchymal stem cells'. Consequently, it is difficult to appreciate the effect of culture expansion and the feasibility of allogeneic transplantation. Based on the sound foundations of pre-clinical research, stem cell-based treatments and protocols have recently emerged. Well-designed prospective clinical trials are needed in order to establish and develop stem cell therapy for bone diseases.

  16. Stem cell aging: mechanisms, regulators and therapeutic opportunities

    PubMed Central

    Oh, Juhyun; Lee, Yang David; Wagers, Amy J

    2014-01-01

    Aging tissues experience a progressive decline in homeostatic and regenerative capacities, which has been attributed to degenerative changes in tissue-specific stem cells, stem cell niches and systemic cues that regulate stem cell activity. Understanding the molecular pathways involved in this age-dependent deterioration of stem cell function will be critical for developing new therapies for diseases of aging that target the specific causes of age-related functional decline. Here we explore key molecular pathways that are commonly perturbed as tissues and stem cells age and degenerate. We further consider experimental evidence both supporting and refuting the notion that modulation of these pathways per se can reverse aging phenotypes. Finally, we ask whether stem cell aging establishes an epigenetic ‘memory’ that is indelibly written or one that can be reset. PMID:25100532

  17. Applications of carbon nanotubes in stem cell research.

    PubMed

    Ramón-Azcón, Javier; Ahadian, Samad; Obregón, Raquel; Shiku, Hitoshi; Ramalingam, Murugan; Matsue, Tomokazu

    2014-10-01

    Stem cells are a key element in tissue engineering and regenerative medicine. However, they require a suitable microenvironment to grow and regenerate. Carbon nanotubes (CNTs) have attracted much attention as promising materials for stem cell research due to their extraordinary properties, such as their extracellular matrix-like structure, high mechanical strength, optical properties, and high electrical conductivity. Of particular interest is the use of CNTs as biomimetic substrates to control the differentiation of stem cells. CNTs have also been combined with commonly used scaffolds to fabricate functional scaffolds to direct stem cell fate. CNTs can also be used for stem cell labeling due to their high optical absorbance in the near-infrared regime. In this paper, we review and discuss the applications of CNTs in stem cell research along with CNT toxicity issues.

  18. Stem Cells in Spinal Fusion

    PubMed Central

    Haudenschild, Dominik R.; Wegner, Adam M.; Klineberg, Eric O.

    2017-01-01

    Study Design: Review of literature. Objectives: This review of literature investigates the application of mesenchymal stem cells (MSCs) in spinal fusion, highlights potential uses in the development of bone grafts, and discusses limitations based on both preclinical and clinical models. Methods: A review of literature was conducted looking at current studies using stem cells for augmentation of spinal fusion in both animal and human models. Results: Eleven preclinical studies were found that used various animal models. Average fusion rates across studies were 59.8% for autograft and 73.7% for stem cell–based grafts. Outcomes included manual palpation and stressing of the fusion, radiography, micro–computed tomography (μCT), and histological analysis. Fifteen clinical studies, 7 prospective and 8 retrospective, were found. Fusion rates ranged from 60% to 100%, averaging 87.1% in experimental groups and 87.2% in autograft control groups. Conclusions: It appears that there is minimal clinical difference between commercially available stem cells and bone marrow aspirates indicating that MSCs may be a good choice in a patient with poor marrow quality. Overcoming morbidity and limitations of autograft for spinal fusion, remains a significant problem for spinal surgeons and further studies are needed to determine the efficacy of stem cells in augmenting spinal fusion. PMID:29238646

  19. Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells.

    PubMed

    García-Prat, Laura; Sousa-Victor, Pedro; Muñoz-Cánoves, Pura

    2013-09-01

    Aging of an organism is associated with the functional decline of tissues and organs, as well as a sharp decline in the regenerative capacity of stem cells. A prevailing view holds that the aging rate of an individual depends on the ratio of tissue attrition to tissue regeneration. Therefore, manipulations that favor the balance towards regeneration may prevent or delay aging. Skeletal muscle is a specialized tissue composed of postmitotic myofibers that contract to generate force. Satellite cells are the adult stem cells responsible for skeletal muscle regeneration. Recent studies on the biology of skeletal muscle and satellite cells in aging have uncovered the critical impact of systemic and niche factors on stem cell functionality and demonstrated the capacity of aged satellite cells to rejuvenate and increase their regenerative potential when exposed to a youthful environment. Here we review the current literature on the coordinated relationship between cell extrinsic and intrinsic factors that regulate the function of satellite cells, and ultimately determine tissue homeostasis and repair during aging, and which encourage the search for new anti-aging strategies. © 2013 The Authors Journal compilation © 2013 FEBS.

  20. Bioreactor engineering of stem cell environments.

    PubMed

    Tandon, Nina; Marolt, Darja; Cimetta, Elisa; Vunjak-Novakovic, Gordana

    2013-11-15

    Stem cells hold promise to revolutionize modern medicine by the development of new therapies, disease models and drug screening systems. Standard cell culture systems have limited biological relevance because they do not recapitulate the complex 3-dimensional interactions and biophysical cues that characterize the in vivo environment. In this review, we discuss the current advances in engineering stem cell environments using novel biomaterials and bioreactor technologies. We also reflect on the challenges the field is currently facing with regard to the translation of stem cell based therapies into the clinic. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Generation of eggs from mouse embryonic stem cells and induced pluripotent stem cells.

    PubMed

    Hayashi, Katsuhiko; Saitou, Mitinori

    2013-08-01

    Oogenesis is an integrated process through which an egg acquires the potential for totipotency, a fundamental condition for creating new individuals. Reconstitution of oogenesis in a culture that generates eggs with proper function from pluripotent stem cells (PSCs) is therefore one of the key goals in basic biology as well as in reproductive medicine. Here we describe a stepwise protocol for the generation of eggs from mouse PSCs, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs and iPSCs are first induced into primordial germ cell-like cells (PGCLCs) that are in turn aggregated with somatic cells of female embryonic gonads, the precursors for adult ovaries. Induction of PGCLCs followed by aggregation with the somatic cells takes up to 8 d. The aggregations are then transplanted under the ovarian bursa, in which PGCLCs grow into germinal vesicle (GV) oocytes in ∼1 month. The PGCLC-derived GV oocytes can be matured into eggs in 1 d by in vitro maturation (IVM), and they can be fertilized with spermatozoa by in vitro fertilization (IVF) to obtain healthy and fertile offspring. This method provides an initial step toward reconstitution of the entire process of oogenesis in vitro.

  2. Stem cells and bone: a historical perspective.

    PubMed

    Bianco, Paolo

    2015-01-01

    Bone physiology and stem cells were tightly intertwined with one another, both conceptually and experimentally, long before the current explosion of interest in stem cells and so-called regenerative medicine. Bone is home to the two best known and best characterized systems of postnatal stem cells, and it is the only organ in which two stem cells and their dependent lineages coordinate the overall adaptive responses of two major physiological systems. All along, the nature and the evolutionary significance of the interplay of bone and hematopoiesis have remained a major scientific challenge, but also allowed for some of the most spectacular developments in cell biology-based medicine, such as hematopoietic stem cell transplantation. This question recurs in novel forms at multiple turning points over time: today, it finds in the biology of the "niche" its popular phrasing. Entirely new avenues of investigation emerge as a new view of bone in physiology and medicine is progressively established. Looking at bone and stem cells in a historical perspective provides a unique case study to highlight the general evolution of science in biomedicine since the end of World War II to the present day. A paradigm shift in science and in its relation to society and policies occurred in the second half of the XXth century, with major implications thereof for health, industry, drug development, market and society. Current interest in stem cells in bone as in other fields is intertwined with that shift. New opportunities and also new challenges arise. This article is part of a Special Issue entitled "Stem cells and bone". Copyright © 2014. Published by Elsevier Inc.

  3. 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

  4. Microgravity-Enhanced Stem Cell Selection

    NASA Technical Reports Server (NTRS)

    Claudio, Pier Paolo; Valluri, Jagan

    2011-01-01

    Stem cells, both embryonic and adult, promise to revolutionize the practice of medicine in the future. In order to realize this potential, a number of hurdles must be overcome. Most importantly, the signaling mechanisms necessary to control the differentiation of stem cells into tissues of interest remain to be elucidated, and much of the present research on stem cells is focused on this goal. Nevertheless, it will also be essential to achieve large-scale expansion and, in many cases, assemble cells in 3D as transplantable tissues. To this end, microgravity analog bioreactors can play a significant role. Microgravity bioreactors were originally conceived as a tool to study the cellular responses to microgravity. However, the technology can address some of the shortcomings of conventional cell culture systems; namely, the deficiency of mass transport in static culture and high mechanical shear forces in stirred systems. Unexpectedly, the conditions created in the vessel were ideal for 3D cell culture. Recently, investigators have demonstrated the capability of the microgravity bioreactors to expand hematopoietic stem cells compared to static culture, and facilitate the differentiation of umbilical cord stem cells into 3D liver aggregates. Stem cells are capable of differentiating into functional cells. However, there are no reliable methods to induce the stem cells to form specific cells or to gain enough cells for transplantation, which limits their application in clinical therapy. The aim of this study is to select the best experimental setup to reach high proliferation levels by culturing these cells in a microgravity-based bioreactor. In typical cell culture, the cells sediment to the bottom surface of their container and propagate as a one-cell-layer sheet. Prevention of such sedimentation affords the freedom for self-assembly and the propagation of 3D tissue arrays. Suspension of cells is easily achievable using stirred technologies. Unfortunately, in

  5. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy

    PubMed Central

    Rocheteau, P.; Chatre, L.; Briand, D.; Mebarki, M.; Jouvion, G.; Bardon, J.; Crochemore, C.; Serrani, P.; Lecci, P. P.; Latil, M.; Matot, B.; Carlier, P. G.; Latronico, N.; Huchet, C.; Lafoux, A.; Sharshar, T.; Ricchetti, M.; Chrétien, F.

    2015-01-01

    Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity. PMID:26666572

  6. Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy.

    PubMed

    Rocheteau, P; Chatre, L; Briand, D; Mebarki, M; Jouvion, G; Bardon, J; Crochemore, C; Serrani, P; Lecci, P P; Latil, M; Matot, B; Carlier, P G; Latronico, N; Huchet, C; Lafoux, A; Sharshar, T; Ricchetti, M; Chrétien, F

    2015-12-15

    Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity.

  7. 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.

  8. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal.

    PubMed

    Ito, Kyoko; Ito, Keisuke

    2016-10-06

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical.

  9. Mesenchymal Stem Cell Therapy for Nonhealing Cutaneous Wounds

    PubMed Central

    Hanson, Summer E.; Bentz, Michael L.; Hematti, Peiman

    2014-01-01

    Summary Chronic wounds remain a major challenge in modern medicine and represent a significant burden, affecting not only physical and mental health, but also productivity, health care expenditure, and long-term morbidity. Even under optimal conditions, the healing process leads to fibrosis or scar. One promising solution, cell therapy, involves the transplantation of progenitor/stem cells to patients through local or systemic delivery, and offers a novel approach to many chronic diseases, including nonhealing wounds. Mesenchymal stem cells are multipotent, adult progenitor cells of great interest because of their unique immunologic properties and regenerative potential. A variety of preclinical and clinical studies have shown that mesenchymal stem cells may have a useful role in wound-healing and tissue-engineering strategies and both aesthetic and reconstructive surgery. Recent advances in stem cell immunobiology can offer insight into the multiple mechanisms through which mesenchymal stem cells could affect underlying pathophysiologic processes associated with nonhealing mesenchymal stem cells. Critical evaluation of the current literature is necessary for understanding how mesenchymal stem cells could potentially revolutionize our approach to skin and soft-tissue defects and designing clinical trials to address their role in wound repair and regeneration. PMID:20124836

  10. 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

  11. 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.

  12. Seeing Stem Cells at Work In Vivo

    PubMed Central

    Srivastava, Amit K.; Bulte, Jeff W. M.

    2013-01-01

    Stem cell based-therapies are novel therapeutic strategies that hold key for developing new treatments for diseases conditions with very few or no cures. Although there has been an increase in the number of clinical trials involving stem cell-based therapies in the last few years, the long-term risks and benefits of these therapies are still unknown. Detailed in vivo studies are needed to monitor the fate of transplanted cells, including their distribution, differentiation, and longevity over time. Advancements in non-invasive cellular imaging techniques to track engrafted cells in real-time present a powerful tool for determining the efficacy of stem cell-based therapies. In this review, we describe the latest approaches to stem cell labeling and tracking using different imaging modalities. PMID:23975604

  13. Cellular and epigenetic drivers of stem cell ageing.

    PubMed

    Ermolaeva, Maria; Neri, Francesco; Ori, Alessandro; Rudolph, K Lenhard

    2018-06-01

    Adult tissue stem cells have a pivotal role in tissue maintenance and regeneration throughout the lifespan of multicellular organisms. Loss of tissue homeostasis during post-reproductive lifespan is caused, at least in part, by a decline in stem cell function and is associated with an increased incidence of diseases. Hallmarks of ageing include the accumulation of molecular damage, failure of quality control systems, metabolic changes and alterations in epigenome stability. In this Review, we discuss recent evidence in support of a novel concept whereby cell-intrinsic damage that accumulates during ageing and cell-extrinsic changes in ageing stem cell niches and the blood result in modifications of the stem cell epigenome. These cumulative epigenetic alterations in stem cells might be the cause of the deregulation of developmental pathways seen during ageing. In turn, they could confer a selective advantage to mutant and epigenetically drifted stem cells with altered self-renewal and functions, which contribute to the development of ageing-associated organ dysfunction and disease.

  14. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

    PubMed

    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  15. Gastric cancer stem cells: A novel therapeutic target

    PubMed Central

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  16. Adult mesenchymal stem cells and cell-based tissue engineering

    PubMed Central

    Tuan, Rocky S; Boland, Genevieve; Tuli, Richard

    2003-01-01

    The identification of multipotential mesenchymal stem cells (MSCs) derived from adult human tissues, including bone marrow stroma and a number of connective tissues, has provided exciting prospects for cell-based tissue engineering and regeneration. This review focuses on the biology of MSCs, including their differentiation potentials in vitro and in vivo, and the application of MSCs in tissue engineering. Our current understanding of MSCs lags behind that of other stem cell types, such as hematopoietic stem cells. Future research should aim to define the cellular and molecular fingerprints of MSCs and elucidate their endogenous role(s) in normal and abnormal tissue functions. PMID:12716446

  17. Our Fat Future: Translating Adipose Stem Cell Therapy.

    PubMed

    Nordberg, Rachel C; Loboa, Elizabeth G

    2015-09-01

    Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research. ©AlphaMed Press.

  18. Directing stem cell trafficking via GPS.

    PubMed

    Sackstein, Robert

    2010-01-01

    The success of stem-cell-based regenerative therapeutics critically hinges on delivering relevant stem/progenitor cells to sites of tissue injury. To achieve adequate parenchymal infiltration following intravascular administration, it is first necessary that circulating cells bind to target tissue endothelium with sufficient strength to overcome the prevailing forces of hemodynamic shear. The principal mediators of these shear-resistant binding interactions consist of a family of C-type lectins known as "selectins" that bind discrete sialofucosylated glycans on their respective ligands. One member of this family, E-selectin, is an endothelial molecule that is inducibly expressed on postcapillary venules at all sites of tissue injury, but is also constitutively expressed on the luminal surface of bone marrow and dermal microvascular endothelium. Most stem/progenitor cells express high levels of CD44, and, in particular, human hematopoietic stem cells express a specialized sialofucosylated glycoform of CD44 known as "hematopoietic cell E-/L-selectin ligand" (HCELL) that functions as a potent E-selectin ligand. This chapter describes a method called "glycosyltransferase-programmed stereosubstitution" (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells that natively lack HCELL. Ex vivo glycan engineering of HCELL via GPS licenses trafficking of infused cells to endothelial beds that express E-selectin, thereby enabling efficient vascular delivery of stem/progenitor cells to sites where they are needed. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Increasing Stem Cell Dose Promotes Posttransplant Immune Reconstitution.

    PubMed

    Xu, Ning; Shen, Sylvie; Dolnikov, Alla

    2017-04-01

    Umbilical cord blood (UCB) transplantation can provide a successful therapeutic option for patients that have no suitable related donor. UCB transplantation is often limited by the relatively small hematopoietic stem cell (HSC) numbers in UCB especially for adult recipients. Early neutrophil and platelet engraftment correlates with the stem cell numbers in UCB transplant. Compared to other HSC sources, immune reconstitution following UCB transplant is slower and complicated by increased frequency of opportunistic infections. The effect of HSC numbers in UCB transplant on immune reconstitution was not thoroughly examined. Using immunocompromised mice transplanted with purified UCB CD34+ stem cells, we have demonstrated that increasing the numbers of CD34+ cells in the transplant promotes hematopoietic and immune reconstitution. At early stages posttransplant, high stem cell dose generated relatively more B cells, while lower dose generated more myeloid and T cells. Thus, the size of the stem cell graft appears to modulate the differentiation potential of infused stem cells. In addition, increasing stem cell dose in the transplant improved CD8+ T cell development and delayed late memory T cell skewing in expense of naive T cells highlighting the importance of HSC dose to maintain the pool of naive T cells able to develop strong immune responses. Transplantation of ex vivo expanded CD34+ cells did not promote, but rather delayed immune reconstitution suggesting the loss of primitive lymphoid precursor cells during ex vivo expansion.

  20. Computational Tools for Stem Cell Biology

    PubMed Central

    Bian, Qin; Cahan, Patrick

    2016-01-01

    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the last several years, a new sub-discipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single-cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. PMID:27318512

  1. Computational Tools for Stem Cell Biology.

    PubMed

    Bian, Qin; Cahan, Patrick

    2016-12-01

    For over half a century, the field of developmental biology has leveraged computation to explore mechanisms of developmental processes. More recently, computational approaches have been critical in the translation of high throughput data into knowledge of both developmental and stem cell biology. In the past several years, a new subdiscipline of computational stem cell biology has emerged that synthesizes the modeling of systems-level aspects of stem cells with high-throughput molecular data. In this review, we provide an overview of this new field and pay particular attention to the impact that single cell transcriptomics is expected to have on our understanding of development and our ability to engineer cell fate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Clinical uses of liver stem cells.

    PubMed

    Dan, Yock Young

    2012-01-01

    Liver transplantation offers a definitive cure for many liver and metabolic diseases. However, the complex invasive procedure and paucity of donor liver graft organs limit its clinical applicability. Liver stem cells provide a potentially limitless source of cells that would be useful for a variety of clinical applications. These stem cells or hepatocytes generated from them can be used in cellular transplantation, bioartificial liver devices and drug testing in the development of new drugs. In this chapter, we review the technical aspects of clinical applications of liver stem cells and the progress made to date in the clinical setting. The difficulties and challenges of realizing the potential of these cells are discussed.

  3. Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta.

    PubMed

    Bamba, Yohei; Nonaka, Masahiro; Sasaki, Natsu; Shofuda, Tomoko; Kanematsu, Daisuke; Suemizu, Hiroshi; Higuchi, Yuichiro; Pooh, Ritsuko K; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

    2017-12-01

    We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology. We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.

  4. Stem Cell Education for Medical Students at Tongji University: Primary Cell Culture and Directional Differentiation of Rat Bone Marrow Mesenchymal Stem Cells

    ERIC Educational Resources Information Center

    Jin, Caixia; Tian, Haibin; Li, Jiao; Jia, Song; Li, Siguang; Xu, Guo-Tong; Xu, Lei; Lu, Lixia

    2018-01-01

    Stem cells are cells that can self-renew and differentiate into a variety of cell types under certain conditions. Stem cells have great potential in regenerative medicine and cell therapy for the treatment of certain diseases. To deliver knowledge about this frontier in science and technology to medical undergraduate students, we designed an…

  5. Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile.

    PubMed

    Jiménez, Gema; Hackenberg, Michael; Catalina, Purificación; Boulaiz, Houria; Griñán-Lisón, Carmen; García, María Ángel; Perán, Macarena; López-Ruiz, Elena; Ramírez, Alberto; Morata-Tarifa, Cynthia; Carrasco, Esther; Aguilera, Margarita; Marchal, Juan Antonio

    2018-08-10

    Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and cancer recurrence, however the involvement of microenvironment is crucial. Here, we have analyzed how human mesenchymal stem cells (MSCs)-derived conditioned medium (CM) affect colon and melanoma CSCs enrichment and maintenance. Our results strongly suggest that the secretome of CM-MSCs selects and maintains subpopulations with high expression of CSCs markers and ALDH1 activity, low proliferation rates with G1 phase arrest, and notably retain in vivo these properties. Cytogenetic analyses indicated that CM-cultured cells contain alterations in chromosome 17 (17q25). Subsequent SKY-FISH analyses suggested that genes located in 17q25 might be involved in stem-cell maintenance. The characterization of secreted proteins present in CM-MSCs revealed that four cytokines and seven growth factors are directly linked to the CSCs enrichment reported in this study. Further analyses revealed that the combination of just IL6 and HGF is enough to provide cancer cells with better stemness properties. In conclusion, this study demonstrates how specific chromosomal alterations present in CSCs subpopulations might represent an advantage for their in vitro maintenance and in vivo stemness properties. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. From fibroblasts and stem cells: implications for cell therapies and somatic cloning.

    PubMed

    Kues, Wilfried A; Carnwath, Joseph W; Niemann, Heiner

    2005-01-01

    Pluripotent embryonic stem cells (ESCs) from the inner cell mass of early murine and human embryos exhibit extensive self-renewal in culture and maintain their ability to differentiate into all cell lineages. These features make ESCs a suitable candidate for cell-replacement therapy. However, the use of early embryos has provoked considerable public debate based on ethical considerations. From this standpoint, stem cells derived from adult tissues are a more easily accepted alternative. Recent results suggest that adult stem cells have a broader range of potency than imagined initially. Although some claims have been called into question by the discovery that fusion between the stem cells and differentiated cells can occur spontaneously, in other cases somatic stem cells have been induced to commit to various lineages by the extra- or intracellular environment. Recent data from our laboratory suggest that changes in culture conditions can expand a subpopulation of cells with a pluripotent phenotype from primary fibroblast cultures. The present paper critically reviews recent data on the potency of somatic stem cells, methods to modify the potency of somatic cells and implications for cell-based therapies.

  7. Lung cells from neonates show a mesenchymal stem cell phenotype.

    PubMed

    Hennrick, Kenneth T; Keeton, Angela G; Nanua, Suparna; Kijek, Theresa G; Goldsmith, Adam M; Sajjan, Umadevi S; Bentley, J Kelley; Lama, Vibha N; Moore, Bethany B; Schumacher, Robert E; Thannickal, Victor J; Hershenson, Marc B

    2007-06-01

    Mesenchymal stem cells have been isolated from adult bone marrow, peripheral blood, adipose tissue, trabecular bone, articular synovium, and bronchial submucosa. We hypothesized that the lungs of premature infants undergoing mechanical ventilation contain fibroblast-like cells with features of mesenchymal stem cells. Tracheal aspirate fluid from mechanically ventilated, premature (< 30 wk gestation) infants 7 days old or younger was obtained from routine suctioning and plated on plastic culture dishes. A total of 11 of 20 patients studied demonstrated fibroblast-like cells, which were identified as early as 6 hours after plating. Cells were found to express the mesenchymal stem cell markers STRO-1, CD73, CD90, CD105, and CD166, as well as CCR2b, CD13, prolyl 4-hydroxylase, and alpha-smooth muscle actin. Cells were negative for the hematopoietic and endothelial cell markers CD11b, CD31, CD34, or CD45. Tracheal aspirate monocyte chemoattractant protein-1/CCL2 levels were ninefold higher in aspirates in which fibroblast-like cells were found, and cells demonstrated chemotaxis in response to monocyte chemoattractant protein. Placement of cells into appropriate media resulted in adipogenic, osteogenic, and myofibroblastic differentiation. Patients from whom mesenchymal stem cells were isolated tended to require more days of mechanical ventilation and supplemental oxygen. Together, these data demonstrate that tracheal aspirate fluid from premature, mechanically ventilated infants contains fibroblasts with cell markers and differentiation potential typically found in mesenchymal stem cells.

  8. In vivo stem cell transplantation using reduced cell numbers.

    PubMed

    Tsutsui, Takeo W

    2015-01-01

    Dental pulp stem cell (DPSC) characterization is essential for regeneration of a dentin/pulp like complex in vivo. This is especially important for identifying the potential of DPSCs to function as stem cells. Previously reported DPSC transplantation methods have used with huge numbers of cells, along with hydroxyapatite/tricalcium phosphate (HA/TCP), gelatin and fibrin, and collagen scaffolds. This protocol describe a transplantation protocol that uses fewer cells and a temperature-responsive cell culture dish.

  9. 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.

  10. Stem-Cell Work Yielding New Approach to Disease: Induced Pluripotent Stem-Cell Research Soars, Spurring Dreams of Clinical Applications.

    PubMed

    Mertz, Leslie

    2016-01-01

    Interest in stem cells escalated in 2006 when scientists figured out how to reprogram some specialized adult cells to assume a stem-cell-like state. Called induced pluripotent stem cells (iPSCs), these cells opened the door to a range of potential applications, including generating cells and tissues to replace those that are faulty or missing in patients with cancer, diabetes, cardiovascular disease, or other maladies (Figure 1). Visions of new treatments and even cures for debilitating and fatal illnesses proliferated, and some of that work is well under way (see "A Wealth of Research"). Now, ten years later, those visions are looking more like real possibilities as research moves from the lab to the clinic and expands toward a greater understanding of the basic science behind stem cells and its applications.

  11. Stem Cells as a Tool for Breast Imaging

    PubMed Central

    Padín-Iruegas, Maria Elena; López López, Rafael

    2012-01-01

    Stem cells are a scientific field of interest due to their therapeutic potential. There are different groups, depending on the differentiation state. We can find lonely stem cells, but generally they distribute in niches. Stem cells don't survive forever. They are affected for senescence. Cancer stem cells are best defined functionally, as a subpopulation of tumor cells that can enrich for tumorigenic property and can regenerate heterogeneity of the original tumor. Circulating tumor cells are cells that have detached from a primary tumor and circulate in the bloodstream. They may constitute seeds for subsequent growth of additional tumors (metastasis) in different tissues. Advances in molecular imaging have allowed a deeper understanding of the in vivo behavior of stem cells and have proven to be indispensable in preclinical and clinical studies. One of the first imaging modalities for monitoring pluripotent stem cells in vivo, magnetic resonance imaging (MRI) offers high spatial and temporal resolution to obtain detailed morphological and functional information. Advantages of radioscintigraphic techniques include their picomolar sensitivity, good tissue penetration, and translation to clinical applications. Radionuclide imaging is the sole direct labeling technique used thus far in human studies, involving both autologous bone marrow derived and peripheral stem cells. PMID:22848220

  12. Efficient Generation of iPS Cells from Skeletal Muscle Stem Cells

    PubMed Central

    Tan, Kah Yong; Eminli, Sarah; Hettmer, Simone; Hochedlinger, Konrad; Wagers, Amy J.

    2011-01-01

    Reprogramming of somatic cells into inducible pluripotent stem cells generally occurs at low efficiency, although what limits reprogramming of particular cell types is poorly understood. Recent data suggest that the differentiation status of the cell targeted for reprogramming may influence its susceptibility to reprogramming as well as the differentiation potential of the induced pluripotent stem (iPS) cells that are derived from it. To assess directly the influence of lineage commitment on iPS cell derivation and differentiation, we evaluated reprogramming in adult stem cell and mature cell populations residing in skeletal muscle. Our data using clonal assays and a second-generation inducible reprogramming system indicate that stem cells found in mouse muscle, including resident satellite cells and mesenchymal progenitors, reprogram with significantly greater efficiency than their more differentiated daughters (myoblasts and fibroblasts). However, in contrast to previous reports, we find no evidence of biased differentiation potential among iPS cells derived from myogenically committed cells. These data support the notion that adult stem cells reprogram more efficiently than terminally differentiated cells, and argue against the suggestion that “epigenetic memory” significantly influences the differentiation potential of iPS cells derived from distinct somatic cell lineages in skeletal muscle. PMID:22028872

  13. Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

    PubMed Central

    Agrawal, Rahul; Dale, Tina P.; Al-Zubaidi, Mohammed A.; Benny Malgulwar, Prit; Forsyth, Nicholas R.; Kulshreshtha, Ritu

    2016-01-01

    MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology. PMID:27783707

  14. Cancer stem cells and cell size: A causal link?

    PubMed

    Li, Qiuhui; Rycaj, Kiera; Chen, Xin; Tang, Dean G

    2015-12-01

    The majority of normal animal cells are 10-20 μm in diameter. Many signaling mechanisms, notably PI3K/Akt/mTOR, Myc, and Hippo pathways, tightly control and coordinate cell growth, cell size, cell division, and cell number during homeostasis. These regulatory mechanisms are frequently deregulated during tumorigenesis resulting in wide variations in cell sizes and increased proliferation in cancer cells. Here, we first review the evidence that primitive stem cells in adult tissues are quiescent and generally smaller than their differentiated progeny, suggesting a correlation between small cell sizes with the stemness. Conversely, increased cell size positively correlates with differentiation phenotypes. We then discuss cancer stem cells (CSCs) and present some evidence that correlates cell sizes with CSC activity. Overall, a causal link between CSCs and cell size is relatively weak and remains to be rigorously assessed. In the future, optimizing methods for isolating cells based on size should help elucidate the connection between cancer cell size and CSC characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. PERSPECTIVES ON CANCER STEM CELLS IN OSTEOSARCOMA

    PubMed Central

    Basu-Roy, Upal; Basilico, Claudio; Mansukhani, Alka

    2012-01-01

    Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. These mesenchymal tumors are derived from progenitor cells in the osteoblast lineage that have accumulated mutations to escape cell cycle checkpoints leading to excessive proliferation and defects in their ability to differentiate appropriately into mature bone-forming osteoblasts. Like other malignant tumors, osteosarcoma is often heterogeneous, consisting of phenotypically distinct cells with features of different stages of differentiation. The cancer stem cell hypothesis posits that tumors are maintained by stem cells and it is the incomplete eradication of a refractory population of tumor-initiating stem cells that accounts for drug resistance and tumor relapse. In this review we present our current knowledge about the biology of osteosarcoma stem cells from mouse and human tumors, highlighting new insights and unresolved issues in the identification of this elusive population. We focus on factors and pathways that are implicated in maintaining such cells, and differences from paradigms of epithelial cancers. Targeting of the cancer stem cells in osteosarcoma is a promising avenue to explore to develop new therapies for this devastating childhood cancer. PMID:22659734

  16. Epithelial stem cells and intestinal cancer.

    PubMed

    Tan, Shawna; Barker, Nick

    2015-06-01

    The mammalian intestine is comprised of an epithelial layer that serves multiple functions in order to maintain digestive activity as well as intestinal homeostasis. This epithelial layer contains highly proliferative stem cells which facilitate its characteristic rapid regeneration. How these stem cells contribute to tissue repair and normal homeostasis are actively studied, and while we have a greater understanding of the molecular mechanisms and cellular locations that underlie stem cell regulation in this tissue, much still remains undiscovered. This review describes epithelial stem cells in both intestinal and non-intestinal tissues, as well as the strategies that have been used to further characterize the cells. Through a discussion of the current understanding of intestinal self-renewal and tissue regeneration in response to injury, we focus on how dysregulation of critical signaling pathways results in potentially oncogenic aberrations, and highlight issues that should be addressed in order for effective intestinal cancer therapies to be devised. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Evaluation of hollow fiber culture for large-scale production of mouse embryonic stem cell-derived hematopoietic stem cells.

    PubMed

    Nakano, Yu; Iwanaga, Shinya; Mizumoto, Hiroshi; Kajiwara, Toshihisa

    2018-03-03

    Hematopoietic stem cells (HSCs) have the ability to differentiate into all types of blood cells and can be transplanted to treat blood disorders. However, it is difficult to obtain HSCs in large quantities because of the shortage of donors. Recent efforts have focused on acquiring HSCs by differentiation of pluripotent stem cells. As a conventional differentiation method of pluripotent stem cells, the formation of embryoid bodies (EBs) is often employed. However, the size of EBs is limited by depletion of oxygen and nutrients, which prevents them from being efficient for the production of HSCs. In this study, we developed a large-scale hematopoietic differentiation approach for mouse embryonic stem (ES) cells by applying a hollow fiber (HF)/organoid culture method. Cylindrical organoids, which had the potential for further spontaneous differentiation, were established inside of hollow fibers. Using this method, we improved the proliferation rate of mouse ES cells to produce an increased HSC population and achieved around a 40-fold higher production volume of HSCs in HF culture than in conventional EB culture. Therefore, the HF/organoid culture method may be a new mass culture method to acquire pluripotent stem cell-derived HSCs.

  18. Commentary: "re-programming or selecting adult stem cells?".

    PubMed

    Trosko, James E

    2008-01-01

    The recent observations that embryonic stemness-associated genes could assist in the "de-differentiation" of adult skin fibroblast cells to "embryonic-like stem cells", using the "somatic cell nuclear transfer" techniques, have been interpreted as indicating a "re-programming" of genes. These reports have demonstrated a "proof of principle" approach to by-pass many, but not all, of the ethical, scientific and medical limitations of the "therapeutic cloning" of embryonic stem cells from embryos. However, while the interpretation that real "re-programming" of all those somatic fibroblastic differentiation genes might be correct, there does exists an alternative hypothesis of these exciting results. Based on the fact that multipotent adult stem cells exist in most, if not all, adult organs, the possibility exists that all these recent "re-programming" results, using the somatic nuclear transfer techniques, actually were the results of transferred rare nuclear material from the adult stem cells residing in the skin of the mouse, monkey and human samples. An examination of the rationale for this challenging hypothesis has been drawn from the hypothesis of the "stem cell theory of cancer", as well as from the field of human adult stem cells research.

  19. Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

    PubMed

    Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

    2010-02-01

    The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

  20. Personalized nanomedicine advancements for stem cell tracking☆

    PubMed Central

    Janowski, Mirek; Bulte, Jeff W.M.; Walczak, Piotr

    2012-01-01

    Recent technological developments in biomedicine have facilitated the generation of data on the anatomical, physiological and molecular level for individual patients and thus introduces opportunity for therapy to be personalized in an unprecedented fashion. Generation of patient-specific stem cells exemplifies the efforts toward this new approach. Cell-based therapy is a highly promising treatment paradigm; however, due to the lack of consistent and unbiased data about the fate of stem cells in vivo, interpretation of therapeutic remains challenging hampering the progress in this field. The advent of nanotechnology with a wide palette of inorganic and organic nanostructures has expanded the arsenal of methods for tracking transplanted stem cells. The diversity of nanomaterials has revolutionized personalized nanomedicine and enables individualized tailoring of stem cell labeling materials for the specific needs of each patient. The successful implementation of stem cell tracking will likely be a significant driving force that will contribute to the further development of nanotheranostics. The purpose of this review is to emphasize the role of cell tracking using currently available nanoparticles. PMID:22820528

  1. Tracking the rise of stem cell tourism.

    PubMed

    Ryan, Kirsten A; Sanders, Amanda N; Wang, Dong D; Levine, Aaron D

    2010-01-01

    Driven by hype surrounding stem cell research, a number of clinics around the world currently offer 'stem cell therapies' to patients. These unproven interventions have attracted policy interest owing to the risks they may pose to patients and to the progress of legitimate translational stem cell research, yet remarkably little data exists about the patients who undergo these unproven therapies or their experiences. We sought to characterize this patient population. We developed a comprehensive data set of blogs written by patients (or their caretakers) about their experiences with unproven stem cell therapies. Analyzing these data suggests that unproven stem cell therapies are increasing rapidly in popularity and are attracting a wide range of patients--both young and old and with a diverse collection of medical conditions. These results should help clinicians advise individual patients and help policymakers devise strategies to mitigate the risks these treatments pose.

  2. Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells.

    PubMed

    Kim, Dae Seong; Lee, Myoung Woo; Lee, Tae-Hee; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

    2017-03-01

    The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm 2 . After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox ( Nanog ), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog ( c-Myc ), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc , were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent). These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

  3. 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.

  4. The regulatory sciences for stem cell-based medicinal products.

    PubMed

    Yuan, Bao-Zhu; Wang, Junzhi

    2014-06-01

    Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

  5. 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

  6. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

    PubMed Central

    Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

    2014-01-01

    The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

  7. Induced Pluripotent Stem Cells and Periodontal Regeneration.

    PubMed

    Du, Mi; Duan, Xuejing; Yang, Pishan

    Periodontitis is a chronic inflammatory disease which leads to destruction of both the soft and hard tissues of the periodontium. Tissue engineering is a therapeutic approach in regenerative medicine that aims to induce new functional tissue regeneration via the synergistic combination of cells, biomaterials, and/or growth factors. Advances in our understanding of the biology of stem cells, including embryonic stem cells and mesenchymal stem cells, have provided opportunities for periodontal tissue engineering. However, there remain a number of limitations affecting their therapeutic efficiency. Due to the considerable proliferation and differentiation capacities, recently described induced pluripotent stem cells (iPSCs) provide a new way for cell-based therapies for periodontal regeneration. This review outlines the latest status of periodontal tissue engineering and highlights the potential use of iPSCs in periodontal tissue regeneration.

  8. Multifaceted Roles of Connexin 43 in Stem Cell Niches.

    PubMed

    Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

    2018-01-01

    Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

  9. 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.

  10. Proteomics Coupled with Metabolite and Cell Wall Profiling Reveal Metabolic Processes of a Developing Rice Stem Internode

    PubMed Central

    Lin, Fan; Williams, Brad J.; Thangella, Padmavathi A. V.; Ladak, Adam; Schepmoes, Athena A.; Olivos, Hernando J.; Zhao, Kangmei; Callister, Stephen J.; Bartley, Laura E.

    2017-01-01

    Internodes of grass stems function in mechanical support, transport, and, in some species, are a major sink organ for carbon in the form of cell wall polymers. This study reports cell wall composition, proteomic, and metabolite analyses of the rice elongating internode. Cellulose, lignin, and xylose increase as a percentage of cell wall material along eight segments of the second rice internode (internode II) at booting stage, from the younger to the older internode segments, indicating active cell wall synthesis. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) of trypsin-digested proteins from this internode at booting reveals 2,547 proteins with at least two unique peptides in two biological replicates. The dataset includes many glycosyltransferases, acyltransferases, glycosyl hydrolases, cell wall-localized proteins, and protein kinases that have or may have functions in cell wall biosynthesis or remodeling. Phospho-enrichment of internode II peptides identified 21 unique phosphopeptides belonging to 20 phosphoproteins including a leucine rich repeat-III family receptor like kinase. GO over-representation and KEGG pathway analyses highlight the abundances of proteins involved in biosynthetic processes, especially the synthesis of secondary metabolites such as phenylpropanoids and flavonoids. LC-MS/MS of hot methanol-extracted secondary metabolites from internode II at four stages (booting/elongation, early mature, mature, and post mature) indicates that internode secondary metabolites are distinct from those of roots and leaves, and differ across stem maturation. This work fills a void of in-depth proteomics and metabolomics data for grass stems, specifically for rice, and provides baseline knowledge for more detailed studies of cell wall synthesis and other biological processes characteristic of internode development, toward improving grass agronomic properties. PMID:28751896

  11. Current status of stem cells in cardiac repair.

    PubMed

    Henning, Robert J

    2018-03-01

    One out of every two men and one out of every three women greater than the age of 40 will experience an acute myocardial infarction (AMI) at some time during their lifetime. As more patients survive their AMIs, the incidence of congestive heart failure (CHF) is increasing. 6 million people in the USA have ischemic cardiomyopathies and CHF. The search for new and innovative treatments for patients with AMI and CHF has led to investigations and use of human embryonic stem cells, cardiac stem/progenitor cells, bone marrow-derived mononuclear cells and mesenchymal stem cells for treatment of these heart conditions. This paper reviews current investigations with human embryonic, cardiac, bone marrow and mesenchymal stem cells, and also stem cell paracrine factors and exosomes.

  12. Gastric Lgr5+ stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice

    PubMed Central

    Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

    2016-01-01

    The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5+ stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5+ stem cells by the inducible Cre-LoxP system and marked mutant Lgr5+ stem cells and their progeny with Cre-reporter Rosa26tdTomato. Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5+ stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5+ chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5+ cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5+ stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression. PMID:27091432

  13. Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.

    PubMed

    Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

    2016-07-01

    The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression.

  14. Engineering Replacement Tissues with Amniotic Stem Cells

    DTIC Science & Technology

    2012-10-01

    compression. J Biomech, 2010. 43(13): p. 2516-23. 17. Gadjanski, I., K. Spiller, and G. Vunjak- Novakovic , Time-dependent processes in stem cell-based...16. Gadjanski, I., K. Spiller, and G. Vunjak- Novakovic , Time-dependent processes in stem cell-based tissue engineering of articular cartilage. Stem

  15. 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.

  16. Stem Cell Transplants in Cancer Treatment

    Cancer.gov

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  17. Training stem cells for treatment of malignant brain tumors

    PubMed Central

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

  18. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

    PubMed Central

    Ito, Kyoko; Ito, Keisuke

    2016-01-01

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

  19. Mechano-adaptation of the stem cell nucleus.

    PubMed

    Heo, Su-Jin; Cosgrove, Brian D; Dai, Eric N; Mauck, Robert L

    2018-01-01

    Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this "mechano-adaptation" are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.

  20. Mechano-adaptation of the stem cell nucleus

    PubMed Central

    Heo, Su-Jin; Cosgrove, Brian D.; Dai, Eric N.; Mauck, Robert L.

    2018-01-01

    ABSTRACT Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this “mechano-adaptation” are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation. PMID:29099288

  1. Natural Killer Cell Immunotherapy Targeting Cancer Stem Cells

    PubMed Central

    Luna, Jesus I; Grossenbacher, Steven K.; Murphy, William J; Canter, Robert J

    2017-01-01

    Introduction Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with “stem-cell” like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. In this report, we review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert Opinion Unlike cytotoxic cancer treatments, NK cells are able to target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells. PMID:27960589

  2. Impact of retrotransposons in pluripotent stem cells.

    PubMed

    Tanaka, Yoshiaki; Chung, Leeyup; Park, In-Hyun

    2012-12-01

    Retrotransposons, which constitute approximately 40% of the human genome, have the capacity to 'jump' across the genome. Their mobility contributes to oncogenesis, evolution, and genomic plasticity of the host genome. Induced pluripotent stem cells as well as embryonic stem cells are more susceptible than differentiated cells to genomic aberrations including insertion, deletion and duplication. Recent studies have revealed specific behaviors of retrotransposons in pluripotent cells. Here, we review recent progress in understanding retrotransposons and provide a perspective on the relationship between retrotransposons and genomic variation in pluripotent stem cells.

  3. Regulation of floral stem cell termination in Arabidopsis

    PubMed Central

    Sun, Bo; Ito, Toshiro

    2015-01-01

    In Arabidopsis, floral stem cells are maintained only at the initial stages of flower development, and they are terminated at a specific time to ensure proper development of the reproductive organs. Floral stem cell termination is a dynamic and multi-step process involving many transcription factors, chromatin remodeling factors and signaling pathways. In this review, we discuss the mechanisms involved in floral stem cell maintenance and termination, highlighting the interplay between transcriptional regulation and epigenetic machinery in the control of specific floral developmental genes. In addition, we discuss additional factors involved in floral stem cell regulation, with the goal of untangling the complexity of the floral stem cell regulatory network. PMID:25699061

  4. Evaluation of the maintenance of stemness, viability, and differentiation potential of gingiva-derived stem-cell spheroids.

    PubMed

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

    2017-05-01

    Gingiva-derived stem cells have been applied for tissue-engineering purposes and may be considered a favorable source of mesenchymal stem cells as harvesting stem cells from the mandible or maxilla may be performed with ease under local anesthesia. The present study was performed to fabricate stem-cell spheroids using concave microwells and to evaluate the maintenance of stemness, viability, and differentiation potential. Gingiva-derived stem cells were isolated, and the stem cells of 4×10 5 (group A) or 8×10 5 (group B) cells were seeded into polydimethylsiloxane-based, concave micromolds with 600 µm diameters. The morphology of the microspheres and the change of the diameters of the spheroids were evaluated. The viability of spheroids was qualitatively analyzed via Live/Dead kit assay. A cell viability analysis was performed on days 1, 3, 6, and 12 with Cell Counting Kit-8. The maintenance of stemness was evaluated with immunocytochemical staining using SSEA-4, TRA-1-60(R) (positive markers), and SSEA-1 (negative marker). Osteogenic, adipogenic, and chondrogenic differentiation potential was evaluated by incubating spheroids in osteogenic, adipogenic and chondrogenic induction medium, respectively. The gingiva-derived stem cells formed spheroids in the concave microwells. The diameters of the spheroids were larger in group A than in group B. The majority of cells in the spheroids emitted green fluorescence, indicating the presence of live cells at day 6. At day 12, the majority of cells in the spheroids emitted green fluorescence, and a small portion of red fluorescence was also noted, which indicated the presence of dead cells. The spheroids were positive for the stem-cell markers SSEA-4 and TRA-1-60(R) and were negative for SSEA-1, suggesting that these spheroids primarily contained undifferentiated human stem cells. Osteogenic, adipogenic, and chondrogenic differentiation was more evident with an increase of incubation time: Mineralized extracellular

  5. Mesenchymal stem cells induce dermal fibroblast responses to injury

    PubMed Central

    Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

    2009-01-01

    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury. PMID:19666021

  6. Mesenchymal stem cells induce dermal fibroblast responses to injury

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

    Smith, Andria N., E-mail: snosmith@u.washington.edu; Willis, Elise, E-mail: elise.willis@gmail.com; Chan, Vincent T.

    2010-01-01

    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. Whenmore » co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.« less

  7. Identification and isolation of adult liver stem/progenitor cells.

    PubMed

    Tanaka, Minoru; Miyajima, Atsushi

    2012-01-01

    Hepatoblasts are considered to be liver stem/progenitor cells in the fetus because they propagate and differentiate into two types of liver epithelial cells, hepatocytes and cholangiocytes. In adults, oval cells that emerge in severely injured liver are considered facultative hepatic stem/progenitor cells. However, the nature of oval cells has remained unclear for long time due to the lack of a method to isolate them. It has also been unclear whether liver stem/progenitor cells exist in normal adult liver. Recently, we and others have successfully identified oval cells and adult liver stem/progenitor cells. Here, we describe the identification and isolation of mouse liver stem/progenitor cells by utilizing antibodies against specific cell surface marker molecules.

  8. Cancer stem cells: beyond Koch's postulates.

    PubMed

    Garcion, Emmanuel; Naveilhan, Philippe; Berger, François; Wion, Didier

    2009-06-08

    Until the last century, infectious diseases were the leading cause of human mortality. Therefore, our current medical reasoning is profoundly influenced by views that originated from medical microbiology. The notion that cancer growth is sustained by a sub-population of particular cells, the cancer stem cells, is highly reminiscent of the germ theory of disease as exemplified by Koch's postulates in the XIXth century. However, accumulating data underscore the importance of cell-cell interactions and tumor environment. Hence it is essential to critically review the basic tenets of the cancer stem cell concept on the light of their relationships with Koch's postulates. Shifting the pathogenic element from a special cellular entity (cancer stem cell or microorganism) to a "pathogenic field" could be critical for curing both cancer and drug-resistant infectious diseases.

  9. Genome editing: a robust technology for human stem cells.

    PubMed

    Chandrasekaran, Arun Pandian; Song, Minjung; Ramakrishna, Suresh

    2017-09-01

    Human pluripotent stem cells comprise induced pluripotent and embryonic stem cells, which have tremendous potential for biological and therapeutic applications. The development of efficient technologies for the targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. Genome editing of stem cells is possible with the help of synthetic nucleases that facilitate site-specific modification of a gene of interest. Recent advances in genome editing techniques have improved the efficiency and speed of the development of stem cells for human disease models. Zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system are powerful tools for editing DNA at specific loci. Here, we discuss recent technological advances in genome editing with site-specific nucleases in human stem cells.

  10. Stem Cell Therapy for the Inner Ear

    PubMed Central

    Okano, Takayuki

    2012-01-01

    In vertebrates, perception of sound, motion, and balance is mediated through mechanosensory hair cells located within the inner ear. In mammals, hair cells are only generated during a short period of embryonic development. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. The goal of this review is to summarize the current state of inner ear stem cell research from a viewpoint of its clinical application for inner ear disorders to illustrate how complementary studies have the potential to promote and refine stem cell therapies for inner ear diseases. The review initially discusses our current understanding of the genetic pathways that regulate hair cell formation from inner ear progenitors during normal development. Subsequent sections discuss the possible use of endogenous inner ear stem cells to induce repair as well as the initial studies aimed at transplanting stem cells into the ear. PMID:22514095

  11. Stem cell education for medical students at Tongji University: Primary cell culture and directional differentiation of rat bone marrow mesenchymal stem cells.

    PubMed

    Jin, Caixia; Tian, Haibin; Li, Jiao; Jia, Song; Li, Siguang; Xu, Guo-Tong; Xu, Lei; Lu, Lixia

    2018-03-01

    Stem cells are cells that can self-renew and differentiate into a variety of cell types under certain conditions. Stem cells have great potential in regenerative medicine and cell therapy for the treatment of certain diseases. To deliver knowledge about this frontier in science and technology to medical undergraduate students, we designed an innovative practical experiment for freshmen in their second semester. The lab exercise focused on rat bone marrow mesenchymal stem cell (BMSC) isolation, cell culture and differentiation, and it aimed to help students master the aseptic techniques for cell culture, the basic methods and procedures for the primary culture and passage of BMSCs, the basic procedure for the directional differentiation of BMSCs into adipocytes and their subsequent identification by oil-red-O staining. This lab exercise is a very meaningful and useful introduction to stem cell collection and manipulation and inspires medical students to deepen their understanding of translational medicine and regenerative medicine. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):151-154, 2018. © 2017 The International Union of Biochemistry and Molecular Biology.

  12. Stem Cell Therapies in Retinal Disorders.

    PubMed

    Garg, Aakriti; Yang, Jin; Lee, Winston; Tsang, Stephen H

    2017-02-02

    Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients' diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

  13. SIRT1 synchs satellite cell metabolism with stem cell fate.

    PubMed

    Diaz-Ruiz, Alberto; Gonzalez-Freire, Marta; Ferrucci, Luigi; Bernier, Michel; de Cabo, Rafael

    2015-02-05

    Metabolic reprogramming of muscle stem cells modulates myogenic cell fate. In this issue of Cell Stem Cell, Ryall et al. (2015) show that SIRT1, a NAD(+)-dependent histone deacetylase, acts as an epigenetic regulator that connects changes in satellite cell metabolism with changes in the transcriptional machinery toward myogenic commitment. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Characterization and comparison of osteoblasts derived from mouse embryonic stem cells and induced pluripotent stem cells.

    PubMed

    Ma, Ming-San; Kannan, Vishnu; de Vries, Anneriek E; Czepiel, Marcin; Wesseling, Evelyn M; Balasubramaniyan, Veerakumar; Kuijer, Roel; Vissink, Arjan; Copray, Sjef C V M; Raghoebar, Gerry M

    2017-01-01

    New developments in stem cell biology offer alternatives for the reconstruction of critical-sized bone defects. One of these developments is the use of induced pluripotent stem (iPS) cells. These stem cells are similar to embryonic stem (ES) cells, but can be generated from adult somatic cells and therefore do not raise ethical concerns. Proper characterization of iPS-derived osteoblasts is important for future development of safe clinical applications of these cells. For this reason, we differentiated mouse ES and iPS cells toward osteoblasts using osteogenic medium and compared their functionality. Immunocytochemical analysis showed significant expression of bone markers (osteocalcin and collagen type I) in osteoblasts differentiated from ES and iPS cells on days 7 and 30. An in vitro mineralization assay confirmed the functionality of osteogenically differentiated ES and iPS cells. Gene expression arrays focusing on osteogenic differentiation were performed in order to compare the gene expression pattern in both differentiated and undifferentiated ES cells and iPS cells. We observed a significant upregulation of osteogenesis-related genes such as Runx2, osteopontin, collagen type I, Tnfsf11, Csf1, and alkaline phosphatase upon osteogenic differentiation of the ES and iPS cells. We further validated the expression of key osteogenic genes Runx2, osteopontin, osteocalcin, collagen type I, and osterix in both differentiated and undifferentiated ES and iPS cells by means of quantified real-time polymerase chain reaction. We conclude that ES and iPS cells are similar in their osteogenic differentiation capacities, as well as in their gene expression patterns.

  15. Perivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering

    PubMed Central

    James, Aaron W.; Zara, Janette N.; Zhang, Xinli; Askarinam, Asal; Goyal, Raghav; Chiang, Michael; Yuan, Wei; Chang, Le; Corselli, Mirko; Shen, Jia; Pang, Shen; Stoker, David; Wu, Ben

    2012-01-01

    Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis. PMID:23197855

  16. Cancer stem cells: impact, heterogeneity, and uncertainty

    PubMed Central

    Magee, Jeffrey A.; Piskounova, Elena; Morrison, Sean J.

    2015-01-01

    The differentiation of tumorigenic cancer stem cells into non-tumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and non-tumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells. In cancers with rapid genetic change, reversible changes in cell states, or biological variability among patients the stem cell model may not be readily testable. PMID:22439924

  17. 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.

  18. Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

    PubMed Central

    Pavon, Lorena Favaro; Sibov, Tatiana Tais; de Oliveira, Daniela Mara; Marti, Luciana C.; Cabral, Francisco Romero; de Souza, Jean Gabriel; Boufleur, Pamela; Malheiros, Suzana M.F.; de Paiva Neto, Manuel A.; da Cruz, Edgard Ferreira; Chudzinski-Tavassi, Ana Marisa; Cavalheiro, Sérgio

    2016-01-01

    Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types. PMID:27244897

  19. Perspectives on avian stem cells for poultry breeding.

    PubMed

    Kagami, Hiroshi

    2016-09-01

    Stem cells have prulipotency to differentiate into many types of cell lineages. Recent progress of avian biotechnology enabled us to analyze the developmental fate of the stem cells: embryonic stem cells / primordial germ cells (PGCs). The stem cells were identified in the central area of the area pellucida of the stage X blastoderms. These cells could be applied for production of germline chimeras and organ regeneration. Generation of medical substrate in transgenic chickens has considerable interests in pharmaceuticals. Sex alteration of the offspring should be enormously beneficial to the poultry industry. Fertilization of the sex-reversed sperm could lead to sexual alteration of the offspring. These strategies using stem cells / PGCs should be one of the most powerful tools for future poultry breeding. © 2016 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

  20. Prostate cancer stem cells: from theory to practice.

    PubMed

    Adamowicz, Jan; Pakravan, Katayoon; Bakhshinejad, Babak; Drewa, Tomasz; Babashah, Sadegh

    2017-04-01

    None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease. Prostate cancer stem cells, which represent only a minimal percentage of the tumor mass, are characterized by a markedly increased clonogenicity and therapeutic resistance. These tumor-initiating cells reside in dynamic niches distributed within the prostate but at a higher concentration in proximal regions of the prostatic ducts. Several markers have been used to identify prostate cancer stem cells. Nevertheless, a definitive profile has not yet been established owing to specificity issues. As cancer stem cells play determining roles in the birth and burst of prostate malignancy, strategies that selectively target them have gained huge clinical attention. Unraveling the mechanisms underlying the physiological functions of cancer stem cells and gaining fundamental insights into their putative involvement in the pathogenesis of prostate tumors provide novel opportunities for the development of efficient and sophisticated therapeutic strategies in the future.

  1. Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes.

    PubMed

    Zhao, Qi; Wang, Xijie; Wang, Shuyan; Song, Zheng; Wang, Jiaxian; Ma, Jing

    2017-03-09

    Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method. It showed that both hESC-CMs and hiPSC-CMs can recapitulate cardiotoxicity and identify the effects of well-characterized compounds. The combined platform of hPSC-CMs and an impedance-based bioanalytical method could improve preclinical cardiotoxicity screening, holding great potential for increasing drug development accuracy.

  2. 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

  3. 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.

  4. The CCR4-NOT complex mediates deadenylation and degradation of stem cell mRNAs and promotes planarian stem cell differentiation.

    PubMed

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology.

  5. The CCR4-NOT Complex Mediates Deadenylation and Degradation of Stem Cell mRNAs and Promotes Planarian Stem Cell Differentiation

    PubMed Central

    Solana, Jordi; Gamberi, Chiara; Mihaylova, Yuliana; Grosswendt, Stefanie; Chen, Chen; Lasko, Paul; Rajewsky, Nikolaus; Aboobaker, A. Aziz

    2013-01-01

    Post-transcriptional regulatory mechanisms are of fundamental importance to form robust genetic networks, but their roles in stem cell pluripotency remain poorly understood. Here, we use freshwater planarians as a model system to investigate this and uncover a role for CCR4-NOT mediated deadenylation of mRNAs in stem cell differentiation. Planarian adult stem cells, the so-called neoblasts, drive the almost unlimited regenerative capabilities of planarians and allow their ongoing homeostatic tissue turnover. While many genes have been demonstrated to be required for these processes, currently almost no mechanistic insight is available into their regulation. We show that knockdown of planarian Not1, the CCR4-NOT deadenylating complex scaffolding subunit, abrogates regeneration and normal homeostasis. This abrogation is primarily due to severe impairment of their differentiation potential. We describe a stem cell specific increase in the mRNA levels of key neoblast genes after Smed-not1 knock down, consistent with a role of the CCR4-NOT complex in degradation of neoblast mRNAs upon the onset of differentiation. We also observe a stem cell specific increase in the frequency of longer poly(A) tails in these same mRNAs, showing that stem cells after Smed-not1 knock down fail to differentiate as they accumulate populations of transcripts with longer poly(A) tails. As other transcripts are unaffected our data hint at a targeted regulation of these key stem cell mRNAs by post-transcriptional regulators such as RNA-binding proteins or microRNAs. Together, our results show that the CCR4-NOT complex is crucial for stem cell differentiation and controls stem cell-specific degradation of mRNAs, thus providing clear mechanistic insight into this aspect of neoblast biology. PMID:24367277

  6. Anti-Cancer Phytometabolites Targeting Cancer Stem Cells

    PubMed Central

    Torquato, Heron F.V.; Goettert, Márcia I.; Justo, Giselle Z.; Paredes-Gamero, Edgar J.

    2017-01-01

    Medicinal plants are a plentiful source of bioactive molecules with much structural diversity. In cancer treatment, molecules obtained from plants represent an attractive alternative to other treatments because several plant-derived compounds have exhibited lower toxicity and higher selectivity against cancer cells. In this review, we focus on the possible application of bioactive molecules obtained from plants against more primitive cell populations in cancers, cancer stem cells. Cancer stem cells are present in several kinds of tumors and are responsible for recurrences and metastases. Common anti-cancer drugs exhibit lower effectiveness against cancer stem cells because of their biological features. However, recently discovered natural phytometabolites exert cytotoxic effects on this rare population of cells in cancers. Therefore, this review presents the latest research on promising compounds from plants that can act as antitumor drugs and that mainly affect stem cell populations in cancers. PMID:28367074

  7. Fetal stem cell transplantation: Past, present, and future

    PubMed Central

    Ishii, Tetsuya; Eto, Koji

    2014-01-01

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson’s disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements. PMID:25258662

  8. Stem cells and cancer of the stomach and intestine.

    PubMed

    Vries, Robert G J; Huch, Meritxell; Clevers, Hans

    2010-10-01

    Cancer in the 21st century has become the number one cause of death in developed countries. Although much progress has been made in improving patient survival, tumour relapse is one of the important causes of cancer treatment failure. An early observation in the study of cancer was the heterogeneity of tumours. Traditionally, this was explained by a combination of genomic instability of tumours and micro environmental factors leading to diverse phenotypical characteristics. It was assumed that cells in a tumour have an equal capacity to propagate the cancer. This model is currently known as the stochastic model. Recently, the Cancer stem cell model has been proposed to explain the heterogeneity of a tumour and its progression. According to this model, the heterogeneity of tumours is the result of aberrant differentiation of tumour cells into the cells of the tissue the tumour originated from. Tumours were suggested to contain stem cell-like cells, the cancer stem cells or tumour-initiating cells, which are uniquely capable of propagating a tumour much like normal stem cells fuel proliferation and differentiation in normal tissue. In this review we discuss the normal stem cell biology of the stomach and intestine followed by both the stochastic and cancer stem cell models in light of recent findings in the gastric and intestinal systems. The molecular pathways underlying normal and tumourigenic growth have been well studied, and recently the stem cells of the stomach and intestine have been identified. Furthermore, intestinal stem cells were identified as the cells-of-origin of colon cancer upon loss of the tumour suppressor APC. Lastly, several studies have proposed the positive identification of a cancer stem cell of human colon cancer. At the end we compare the cancer stem cell model and the stochastic model. We conclude that clonal evolution of tumour cells resulting from genetic mutations underlies tumour initiation and progression in both cancer models. This

  9. Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics

    PubMed Central

    Lin, Sabrina C.; Bays, Brett C.; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

    2016-01-01

    There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells. PMID:26848582

  10. Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics.

    PubMed

    Zahedi, Atena; On, Vincent; Lin, Sabrina C; Bays, Brett C; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

    2016-01-01

    There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells.

  11. Stem cell-biomaterial interactions for regenerative medicine.

    PubMed

    Martino, Sabata; D'Angelo, Francesco; Armentano, Ilaria; Kenny, Josè Maria; Orlacchio, Aldo

    2012-01-01

    The synergism of stem cell biology and biomaterial technology promises to have a profound impact on stem-cell-based clinical applications for tissue regeneration. Biomaterials development is rapidly advancing to display properties that, in a precise and physiological fashion, could drive stem-cell fate both in vitro and in vivo. Thus, the design of novel materials is trying to recapitulate the molecular events involved in the production, clearance and interaction of molecules within tissue in pathologic conditions and regeneration of tissue/organs. In this review we will report on the challenges behind translating stem cell biology and biomaterial innovations into novel clinical therapeutic applications for tissue and organ replacements (graphical abstract). Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Integrating physiological regulation with stem cell and tissue homeostasis

    PubMed Central

    Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

    2015-01-01

    Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

  13. Effects of Mesenchymal Stem Cell Derivatives on Hematopoiesis and Hematopoietic Stem Cells

    PubMed Central

    Aqmasheh, Sara; Shamsasanjan, karim; Akbarzadehlaleh, Parvin; Pashoutan Sarvar, Davod; Timari, Hamze

    2017-01-01

    Hematopoiesis is a balance among quiescence, self-renewal, proliferation, and differentiation, which is believed to be firmly adjusted through interactions between hematopoietic stem and progenitor cells (HSPCs) with the microenvironment. This microenvironment is derived from a common progenitor of mesenchymal origin and its signals should be capable of regulating the cellular memory of transcriptional situation and lead to an exchange of stem cell genes expression. Mesenchymal stem cells (MSCs) have self-renewal and differentiation capacity into tissues of mesodermal origin, and these cells can support hematopoiesis through release various molecules that play a crucial role in migration, homing, self-renewal, proliferation, and differentiation of HSPCs. Studies on the effects of MSCs on HSPC differentiation can develop modern solutions in the treatment of patients with hematologic disorders for more effective Bone Marrow (BM) transplantation in the near future. However, considerable challenges remain on realization of how paracrine mechanisms of MSCs act on the target tissues, and how to design a therapeutic regimen with various paracrine factors in order to achieve optimal results for tissue conservation and regeneration. The aim of this review is to characterize and consider the related aspects of the ability of MSCs secretome in protection of hematopoiesis. PMID:28761818

  14. Therapeutics from Adult Stem Cells and the Hype Curve.

    PubMed

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment.

  15. Mycoplasma Infection Alters Cancer Stem Cell Properties in Vitro.

    PubMed

    Gedye, Craig; Cardwell, Tracy; Dimopoulos, Nektaria; Tan, Bee Shin; Jackson, Heather; Svobodová, Suzanne; Anaka, Matthew; Behren, Andreas; Maher, Christopher; Hofmann, Oliver; Hide, Winston; Caballero, Otavia; Davis, Ian D; Cebon, Jonathan

    2016-02-01

    Cancer cell lines can be useful to model cancer stem cells. Infection with Mycoplasma species is an insidious problem in mammalian cell culture. While investigating stem-like properties in early passage melanoma cell lines, we noted poorly reproducible results from an aliquot of a cell line that was later found to be infected with Mycoplasma hyorhinis. Deliberate infection of other early passage melanoma cell lines aliquots induced variable and unpredictable effects on expression of putative cancer stem cell markers, clonogenicity, proliferation and global gene expression. Cell lines established in stem cell media (SCM) were equally susceptible. Mycoplasma status is rarely reported in publications using cultured cells to study the cancer stem cell hypothesis. Our work highlights the importance of surveillance for Mycoplasma infection while using any cultured cells to interrogate tumor heterogeneity.

  16. Cord Blood Stem Cell Procurement in Minority Donors

    DTIC Science & Technology

    2006-03-01

    stem cell transplantation centers worldwide. Cord blood is a readily available source of hematopoietic stem cells that is more accessible than other...matched donor and CBU allows less stringent matching. Thus, CBU is a rapid solution to patients who are in urgent need of stem cell transplantation and no

  17. mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions

    NASA Astrophysics Data System (ADS)

    Matsubara, Shyuichiro; Ding, Qiang; Miyazaki, Yumi; Kuwahata, Taisaku; Tsukasa, Koichiro; Takao, Sonshin

    2013-11-01

    Pancreatic cancer is characterized by near-universal mutations in KRAS. The mammalian target of rapamycin (mTOR), which functions downstream of RAS, has divergent effects on stem cells. In the present study, we investigated the significance of the mTOR pathway in maintaining the properties of pancreatic cancer stem cells. The mTOR inhibitor, rapamycin, reduced the viability of CD133+ pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Further, rapamycin had different effects on CD133+ cells compared to cyclopamine which is an inhibitor of the Hedgehog pathway. Thus, the mTOR pathway has a distinct role although both pathways maintain pancreatic cancer stem cells. Therefore, mTOR might be a promising target to eliminate pancreatic cancer stem cells.

  18. Hematopoietic stem cell origin of connective tissues.

    PubMed

    Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

    2010-07-01

    Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications. Copyright 2010 ISEH - Society for Hematology and Stem Cells. All rights reserved.

  19. Human stem cells for craniomaxillofacial reconstruction.

    PubMed

    Jalali, Morteza; Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor; Pauklin, Siim; Vallier, Ludovic

    2014-07-01

    Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction.

  20. Human Stem Cells for Craniomaxillofacial Reconstruction

    PubMed Central

    Kirkpatrick, William Niall Alexander; Cameron, Malcolm Gregor

    2014-01-01

    Human stem cell research represents an exceptional opportunity for regenerative medicine and the surgical reconstruction of the craniomaxillofacial complex. The correct architecture and function of the vastly diverse tissues of this important anatomical region are critical for life supportive processes, the delivery of senses, social interaction, and aesthetics. Craniomaxillofacial tissue loss is commonly associated with inflammatory responses of the surrounding tissue, significant scarring, disfigurement, and psychological sequelae as an inevitable consequence. The in vitro production of fully functional cells for skin, muscle, cartilage, bone, and neurovascular tissue formation from human stem cells, may one day provide novel materials for the reconstructive surgeon operating on patients with both hard and soft tissue deficit due to cancer, congenital disease, or trauma. However, the clinical translation of human stem cell technology, including the application of human pluripotent stem cells (hPSCs) in novel regenerative therapies, faces several hurdles that must be solved to permit safe and effective use in patients. The basic biology of hPSCs remains to be fully elucidated and concerns of tumorigenicity need to be addressed, prior to the development of cell transplantation treatments. Furthermore, functional comparison of in vitro generated tissue to their in vivo counterparts will be necessary for confirmation of maturity and suitability for application in reconstructive surgery. Here, we provide an overview of human stem cells in disease modeling, drug screening, and therapeutics, while also discussing the application of regenerative medicine for craniomaxillofacial tissue deficit and surgical reconstruction. PMID:24564584

  1. Dicer in Mammary Tumor Stem Cell Maintenance

    DTIC Science & Technology

    2006-03-01

    we are cloning small RNAs from mammary stem cells in order to determine the regulatory niches that miRNAs may fill in this cell type. Our ultimate goal is to assess the role of Dicer in mammary tumor stem cell maintenance.

  2. Stem Cell Niche, the Microenvironment and Immunological Crosstalk

    PubMed Central

    Sujata, Law; Chaudhuri, S

    2008-01-01

    The concept of stem cells, their physiological existence, the intricate anatomical localization, the known and the unknown functions, and their exclusive utility for the purpose of regenerative medicine, are all now encompassed within an emergent question, ‘how compatible these cells are immunologically?' Indeed, the medical aspects of stem cells are dependent on a large number of queries based on the basic properties of the cells. It has greatly been emphasized to probe into the basic research on stem cells before any successful therapeutic attempts are made. One of the intricate aspects of the adult stem cells is its immunological behavior in relation to the microenvironmental associates, the stromal cells in the presence of a suitable target. PMID:18445340

  3. Stem cell niche, the microenvironment and immunological crosstalk.

    PubMed

    Sujata, Law; Chaudhuri, S

    2008-04-01

    The concept of stem cells, their physiological existence, the intricate anatomical localization, the known and the unknown functions, and their exclusive utility for the purpose of regenerative medicine, are all now encompassed within an emergent question, 'how compatible these cells are immunologically?' Indeed, the medical aspects of stem cells are dependent on a large number of queries based on the basic properties of the cells. It has greatly been emphasized to probe into the basic research on stem cells before any successful therapeutic attempts are made. One of the intricate aspects of the adult stem cells is its immunological behavior in relation to the microenvironmental associates, the stromal cells in the presence of a suitable target.

  4. 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.

  5. Discovering monotonic stemness marker genes from time-series stem cell microarray data.

    PubMed

    Wang, Hsei-Wei; Sun, Hsing-Jen; Chang, Ting-Yu; Lo, Hung-Hao; Cheng, Wei-Chung; Tseng, George C; Lin, Chin-Teng; Chang, Shing-Jyh; Pal, Nikhil; Chung, I-Fang

    2015-01-01

    Identification of genes with ascending or descending monotonic expression patterns over time or stages of stem cells is an important issue in time-series microarray data analysis. We propose a method named Monotonic Feature Selector (MFSelector) based on a concept of total discriminating error (DEtotal) to identify monotonic genes. MFSelector considers various time stages in stage order (i.e., Stage One vs. other stages, Stages One and Two vs. remaining stages and so on) and computes DEtotal of each gene. MFSelector can successfully identify genes with monotonic characteristics. We have demonstrated the effectiveness of MFSelector on two synthetic data sets and two stem cell differentiation data sets: embryonic stem cell neurogenesis (ESCN) and embryonic stem cell vasculogenesis (ESCV) data sets. We have also performed extensive quantitative comparisons of the three monotonic gene selection approaches. Some of the monotonic marker genes such as OCT4, NANOG, BLBP, discovered from the ESCN dataset exhibit consistent behavior with that reported in other studies. The role of monotonic genes found by MFSelector in either stemness or differentiation is validated using information obtained from Gene Ontology analysis and other literature. We justify and demonstrate that descending genes are involved in the proliferation or self-renewal activity of stem cells, while ascending genes are involved in differentiation of stem cells into variant cell lineages. We have developed a novel system, easy to use even with no pre-existing knowledge, to identify gene sets with monotonic expression patterns in multi-stage as well as in time-series genomics matrices. The case studies on ESCN and ESCV have helped to get a better understanding of stemness and differentiation. The novel monotonic marker genes discovered from a data set are found to exhibit consistent behavior in another independent data set, demonstrating the utility of the proposed method. The MFSelector R function and data

  6. 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

  7. Functional characterization of human pluripotent stem cell-derived arterial endothelial cells.

    PubMed

    Zhang, Jue; Chu, Li-Fang; Hou, Zhonggang; Schwartz, Michael P; Hacker, Timothy; Vickerman, Vernella; Swanson, Scott; Leng, Ning; Nguyen, Bao Kim; Elwell, Angela; Bolin, Jennifer; Brown, Matthew E; Stewart, Ron; Burlingham, William J; Murphy, William L; Thomson, James A

    2017-07-25

    Here, we report the derivation of arterial endothelial cells from human pluripotent stem cells that exhibit arterial-specific functions in vitro and in vivo. We combine single-cell RNA sequencing of embryonic mouse endothelial cells with an EFNB2-tdTomato/EPHB4-EGFP dual reporter human embryonic stem cell line to identify factors that regulate arterial endothelial cell specification. The resulting xeno-free protocol produces cells with gene expression profiles, oxygen consumption rates, nitric oxide production levels, shear stress responses, and TNFα-induced leukocyte adhesion rates characteristic of arterial endothelial cells. Arterial endothelial cells were robustly generated from multiple human embryonic and induced pluripotent stem cell lines and have potential applications for both disease modeling and regenerative medicine.

  8. Programming Retinal Stem Cells into Cone Photoreceptors

    DTIC Science & Technology

    2015-12-01

    AWARD NUMBER: W81XWH-14-1-0566 TITLE: Programming Retinal Stem Cells into Cone Photoreceptors PRINCIPAL INVESTIGATOR: Joseph A. Brzezinski IV...SUBTITLE 5a. CONTRACT NUMBER Programming Retinal Stem Cells into Cone Photoreceptors 5b. GRANT NUMBER W81XWH-14-1-0566 5c. PROGRAM ELEMENT NUMBER 6...to program human stem cells directly into cones. Using RNA-seq, we identified several genes that are upregulated in advance of the earliest

  9. Neural Stem Cells Derived Directly from Adipose Tissue.

    PubMed

    Petersen, Eric D; Zenchak, Jessica R; Lossia, Olivia V; Hochgeschwender, Ute

    2018-05-01

    Neural stem cells (NSCs) are characterized as self-renewing cell populations with the ability to differentiate into the multiple tissue types of the central nervous system. These cells can differentiate into mature neurons, astrocytes, and oligodendrocytes. This category of stem cells has been shown to be a promisingly effective treatment for neurodegenerative diseases and neuronal injury. Most treatment studies with NSCs in animal models use embryonic brain-derived NSCs. This approach presents both ethical and feasibility issues for translation to human patients. Adult tissue is a more practical source of stem cells for transplantation therapies in humans. Some adult tissues such as adipose tissue and bone marrow contain a wide variety of stem cell populations, some of which have been shown to be similar to embryonic stem cells, possessing many pluripotent properties. Of these stem cell populations, some are able to respond to neuronal growth factors and can be expanded in vitro, forming neurospheres analogous to cells harvested from embryonic brain tissue. In this study, we describe a method for the collection and culture of cells from adipose tissue that directly, without going through intermediates such as mesenchymal stem cells, results in a population of NSCs that are able to be expanded in vitro and be differentiated into functional neuronal cells. These adipose-derived NSCs display a similar phenotype to those directly derived from embryonic brain. When differentiated into neurons, cells derived from adipose tissue have spontaneous spiking activity with network characteristics similar to that of neuronal cultures.

  10. Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells.

    PubMed

    Barbet, Romain; Peiffer, Isabelle; Hatzfeld, Antoinette; Charbord, Pierre; Hatzfeld, Jacques A

    2011-01-01

    We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated that hES-MSCs express the sarcomeric muscle lineage in addition to the classical mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript analysis of membrane antigens suggests that IL1R1(low), BMPR1B(low), FLT4(low), LRRC32(low), and CD34 may be good candidates for the detection and isolation of the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6, IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role for these cytokines in the paracrine control of stem cell niches. Our database may be shared with other laboratories in order to explore the considerable clinical potential of hES-MSCs, which appear to represent an intermediate developmental stage between hESCs and hMSCs.

  11. 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

  12. Tissue damage-induced intestinal stem cell division in Drosophila

    PubMed Central

    Amcheslavsky, Alla; Jiang, Jin; Ip, Y. Tony

    2009-01-01

    SUMMARY Stem cell division is essential for tissue integrity during growth, aging, and pathogenic assaults. Adult gastrointestinal tract encounters numerous stimulations and impaired tissue regeneration may lead to inflammatory diseases and cancer. Intestinal stem cells in adult Drosophila have recently been identified and shown to replenish the various cell types within the midgut. However, it is not known whether these intestinal stem cells can respond to environmental challenges. By feeding dextran sulfate sodium and bleomycin to flies and by expressing apoptotic proteins, we show that Drosophila intestinal stem cells can increase the rate of division in response to tissue damage. Moreover, if tissue damage results in epithelial cell loss, the newly formed enteroblasts can differentiate into mature epithelial cells. By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division. PMID:19128792

  13. Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

    PubMed Central

    Yang, Jian; Darley, Richard L; Hallett, Maurice; Evans, W Howard

    2009-01-01

    Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells and in monocytes and granulocytes in bone marrow and spinal cord. Reverse transcriptase-polymerase chain reaction (RT-PCR) detected only low expression of Cx43 and Cx37. Very low level dye coupling was detected by flow cytometry between CD34+ cells and other Cx43 expressing cells, including HL-1 cardiac cells, and was not inhibited by specific gap junction inhibitors. The results indicate that CD34+ cells are unlikely to communicate via gap junctions and the authors conclude that use of CD34+ cells to repair damaged hearts is unlikely to involve gap junctions. The results concur with the hypothesis that bone marrow cells elicit improved cardiac function through release of undefined paracrine mediators. PMID:20298144

  14. Stem cell research: applicability in dentistry.

    PubMed

    Mathur, Shivani; Chopra, Rahul; Pandit, I K; Srivastava, Nikhil; Gugnani, Neeraj

    2014-01-01

    In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, the inability of most tissues and organs to repair and regenerate after damage is a problem that needs to be solved. Stem cell research is being pursued in the hope of achieving major medical breakthroughs. Scientists are striving to create therapies that rebuild or replace damaged cells with tissues grown from stem cells that will offer hope to people suffering from various ailments. Regeneration of damaged periodontal tissue, bone, pulp, and dentin is a problem that dentists face today. Stem cells present in dental pulp, periodontal ligament, and alveolar bone marrow have the potential to repair and regenerate teeth and periodontal structures. These stem cells can be harvested from dental pulp, periodontal ligament, and/or alveolar bone marrow; expanded; embedded in an appropriate scaffold; and transplanted back into a defect to regenerate bone and tooth structures. These cells have the potential to regenerate dentin, periodontal ligament, and cementum and can also be used to restore bone defects. The kind of scaffold, the source of cells, the type of in vitro culturing, and the type of surgical procedure to be used all require careful consideration. The endeavor is clearly multidisciplinary in nature, and the practicing dental surgeon has a critical role in it. Playing this role in the most effective way requires awareness of the huge potential associated with the use of stem cells in a clinical setting, as well as a proper understanding of the related problems.

  15. The Protein Corona around Nanoparticles Facilitates Stem Cell Labeling for Clinical MR Imaging.

    PubMed

    Nejadnik, Hossein; Taghavi-Garmestani, Seyed-Meghdad; Madsen, Steven J; Li, Kai; Zanganeh, Saeid; Yang, Phillip; Mahmoudi, Morteza; Daldrup-Link, Heike E

    2018-03-01

    Purpose To evaluate if the formation of a protein corona around ferumoxytol nanoparticles can facilitate stem cell labeling for in vivo tracking with magnetic resonance (MR) imaging. Materials and Methods Ferumoxytol was incubated in media containing human serum (group 1), fetal bovine serum (group 2), StemPro medium (group 3), protamine (group 4), and protamine plus heparin (group 5). Formation of a protein corona was characterized by means of dynamic light scattering, ζ potential, and liquid chromatography-mass spectrometry. Iron uptake was evaluated with 3,3'-diaminobenzidine-Prussian blue staining, lysosomal staining, and inductively coupled plasma spectrometry. To evaluate the effect of a protein corona on stem cell labeling, human mesenchymal stem cells (hMSCs) were labeled with the above formulations, implanted into pig knee specimens, and investigated with T2-weighted fast spin-echo and multiecho spin-echo sequences on a 3.0-T MR imaging unit. Data in different groups were compared by using a Kruskal-Wallis test. Results Compared with bare nanoparticles, all experimental groups showed significantly increased negative ζ values (from -37 to less than -10; P = .008). Nanoparticles in groups 1-3 showed an increased size because of the formation of a protein corona. hMSCs labeled with group 1-5 media showed significantly shortened T2 relaxation times compared with unlabeled control cells (P = .0012). hMSCs labeled with group 3 and 5 media had the highest iron uptake after cells labeled with group 1 medium. After implantation into pig knees, hMSCs labeled with group 1 medium showed significantly shorter T2 relaxation times than hMSCs labeled with group 2-5 media (P = .0022). Conclusion The protein corona around ferumoxytol nanoparticles can facilitate stem cell labeling for clinical cell tracking with MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

  16. Stem cell homing-based tissue engineering using bioactive materials

    NASA Astrophysics Data System (ADS)

    Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

    2017-06-01

    Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

  17. Induction of pluripotent stem cells from fibroblast cultures.

    PubMed

    Takahashi, Kazutoshi; Okita, Keisuke; Nakagawa, Masato; Yamanaka, Shinya

    2007-01-01

    Clinical application of embryonic stem (ES) cells faces difficulties regarding use of embryos, as well as tissue rejection after implantation. One way to circumvent these issues is to generate pluripotent stem cells directly from somatic cells. Somatic cells can be reprogrammed to an embryonic-like state by the injection of a nucleus into an enucleated oocyte or by fusion with ES cells. However, little is known about the mechanisms underlying these processes. We have recently shown that the combination of four transcription factors can generate ES-like pluripotent stem cells directly from mouse fibroblast cultures. The cells, named induced pluripotent stem (iPS) cells, can be differentiated into three germ layers and committed to chimeric mice. Here we describe detailed methods and tips for the generation of iPS cells.

  18. Stem cells and regenerative medicine on the Asian horizon: an economic, industry and social perspective.

    PubMed

    Sipp, Douglas

    2009-11-01

    For the past decade, forays into stem cell research and regenerative medicine by institutes and companies based in the Asia-Pacific region have attracted global attention at levels unprecedented in the life sciences. The unique combination of economic pressures, competitiveness and opportunism, laissez-faire regulation, burgeoning investment in the life sciences and rapidly growing markets, coupled with its great diversity, have propelled the region to surge forward in some areas, but to stumble in others. This article provides a historical and scientific context to the state of stem cell research and clinical applications in the region, and highlights trends and new possibilities to watch for on the Asian horizon.

  19. 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.

  20. [Cell therapy for Parkinson's disease: III. Neonatal, fetal and embryonic stem cell-based applications].

    PubMed

    Anisimov, S V

    2009-01-01

    Motor dysfunctions in Parkinson's disease are believed to be primarily due to the degeneration of dopaminergic neurons located in the substantia nigra pars compacta. Numerous cell replacement therapy approaches have been developed and tested, including these based on donor cell transplantation (embryonic and adult tissue-derived), adult mesenchymal stem cells (hMSCs)-, neural stem cells (hNSCs)- and finally human embryonic stem cells (hESCs)-based. Despite the progress achieved, numerous difficulties prevent wider practical application of stem cell-based therapy approaches for the treatment of Parkinson's disease. Among the latter, ethical, safety and technical issues stand out. Current series of reviews (Cell therapy for Parkinson's disease: I. Embryonic and adult donor tissue-based applications; II. Adult stem cell-based applications; III. Neonatal, fetal and embryonic stem cell-based applications; IV. Risks and future trends) aims providing a balanced and updated view on various issues associated with cell types (including stem cells) in regards to their potential in the treatment of Parkinson's disease. Essential features of the individual cell subtypes, principles of available cell handling protocols, transplantation, and safety issues are discussed extensively.