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Sample records for stem cell evidence

  1. Uterine stem cells: what is the evidence?

    PubMed

    Gargett, C E

    2007-01-01

    The mucosal lining (endometrium) of the human uterus undergoes cyclical processes of regeneration, differentiation and shedding as part of the menstrual cycle. Endometrial regeneration also follows parturition, almost complete resection and in post-menopausal women taking estrogen replacement therapy. In non-menstruating species, there are cycles of endometrial growth and apoptosis rather than physical shedding. The concept that endometrial stem/progenitor cells are responsible for the remarkable regenerative capacity of endometrium was proposed many years ago. However, attempts to isolate, characterize and locate endometrial stem cells have only been undertaken in the last few years as experimental approaches to identify adult stem/progenitor cells in other tissues have been developed. Adult stem cells are defined by their functional properties rather than by marker expression. Evidence for the existence of adult stem/progenitor cells in human and mouse endometrium is now emerging because functional stem cell assays are being applied to uterine cells and tissues. These fundamental studies on endometrial stem/progenitor cells will provide new insights into the pathophysiology of various gynaecological disorders associated with abnormal endometrial proliferation, including endometrial cancer, endometrial hyperplasia, endometriosis and adenomyosis. PMID:16960017

  2. Stem Cells

    MedlinePlus

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

  3. 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 ...

  4. Lymphoma stem cells: enough evidence to support their existence?

    PubMed Central

    Martinez-Climent, Jose A.; Fontan, Lorena; Gascoyne, Randy D.; Siebert, Reiner; Prosper, Felipe

    2010-01-01

    While leukemia-originating stem cells are critical in the initiation and maintenance of leukemias, the existence of similar cell populations that may generate B-cell lymphoma upon mutation remains uncertain. Here we propose that committed lymphoid progenitor/precursor cells with an active V-D-J recombination program are the initiating cells of follicular lymphoma and mantle cell lymphoma when targeted by immunoglobulin (IG)- gene translocations in the bone marrow. However, these pre-malignant lymphoma-initiating cells cannot drive complete malignant transformation, requiring additional cooperating mutations in specific stem-cell programs to be converted into the lymphoma-originating cells able to generate and sustain lymphoma development. Conversely, diffuse large B-cell lymphoma and sporadic Burkitt’s lymphoma derive from B lymphocytes that acquire translocations through IG-hyper-mutation or class-switching errors within the germinal center. Although secondary reprogramming mutations are generally required, some cells such as centroblasts or memory B cells that have certain stem cell-like features, or lymphocytes with MYC rearrangements that deregulate self-renewal pathways, may bypass this need and directly function as the lymphoma-originating cells. An alternative model supports an aberrant epigenetic modification of gene sets as the first occurring hit, which either leads to retaining stem-cell features in hematopoietic stem or progenitor cells, or reprograms stemness into more committed lymphocytes, followed by secondary chromosomal translocations that eventually drive lymphoma development. Isolation and characterization of the cells that are at the origin of the different B-cell non-Hodgkin’s lymphomas will provide critical insights into the disease pathogenesis and will represent a step towards the development of more effective therapies. PMID:20139392

  5. Gastric cancer stem cells: evidence, potential markers, and clinical implications.

    PubMed

    Brungs, Daniel; Aghmesheh, Morteza; Vine, Kara L; Becker, Therese M; Carolan, Martin G; Ranson, Marie

    2016-04-01

    Gastric cancer is a significant global health problem. It is the fifth most common cancer and third leading cause of cancer-related death worldwide (Torre et al. in CA Cancer J Clin 65(2):87-108, 2015). Despite advances in treatment, overall prognosis remains poor, due to tumour relapse and metastasis. There is an urgent need for novel therapeutic approaches to improve clinical outcomes in gastric cancer. The cancer stem cell (CSC) model has been proposed to explain the high rate of relapse and subsequent resistance of cancer to current systemic treatments (Vermeulen et al. in Lancet Oncol 13(2):e83-e89, 2012). CSCs have been identified in many solid malignancies, including gastric cancer, and have significant clinical implications, as targeting the CSC population may be essential in preventing the recurrence and spread of a tumour (Dewi et al. in J Gastroenterol 46(10):1145-1157, 2011). This review seeks to summarise the current evidence for CSC in gastric cancer, with an emphasis on candidate CSC markers, clinical implications, and potential therapeutic approaches. PMID:26428661

  6. Types of Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  7. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells.

    PubMed

    Jones, Anna J; Gokhale, Paul J; Allison, Thomas F; Sampson, Barry; Athwal, Sharan; Grant, Simon; Andrews, Peter W; Allen, Nicholas D; Case, C Patrick

    2015-01-01

    Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular 'bystander signalling' both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development. PMID:26170169

  8. Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells

    PubMed Central

    Jones, Anna J; Gokhale, Paul J; Allison, Thomas F; Sampson, Barry; Athwal, Sharan; Grant, Simon; Andrews, Peter W; Allen, Nicholas D; Patrick Case, C

    2015-01-01

    Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular ‘bystander signalling’ both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development. PMID:26170169

  9. Stem Cell Basics

    MedlinePlus

    ... stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before ... two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells . ...

  10. Learn About Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... ISSCR Get Involved Media © 2015 International Society for Stem Cell Research Terms of Use Disclaimer Privacy Policy

  11. Child-rearing and adult leukemia: Epidemiologic evidence in support of competing hematopoietic stem cell differentiation

    SciTech Connect

    Steven, R.G. ); Severson, R.K. . Japan-Hawaii Cancer Study); Heuser, L. )

    1988-05-01

    The hypothesis that lack of child-rearing increases the risk of acute non-lymphocytic leukemia (ANLL) in adults was examined in a case-control study in western Washington State. Among 159 study subjects over age 50 in 1985, there were 76 cases of ANLL and 83 controls. The crude odds ratio associated with lack of child-rearing was 1.8, with a 95% confidence range of 0.7 to 5.0. The average total number of children ever living with cases was 2.6 and with controls was 3.1 (p = 0.06). The mean total number of years living with a child, or children, under age 18 was 17.6 in cases and 20.2 in controls (p = 0.05). These results were not materially altered after adjustment for age, smoking, race, income, and sex. The data provide evidence that cases of ANLL were less likely to ever have had children and that fewer years were spent rearing children than were spent by controls. The hypothesis was based on the competing stem cell'' theory of hematopoietic ontogeny. If valid, then exposure to children would increase exposure to infection, leading to increased lymphocytic stem cell turnover, and decreased non-lymphocytic stem cell turnover. This, in turn, may reduce risk of ANLL in adults. 18 refs., 3 tabs.

  12. Preclinical and clinical evidence for stem cell therapies as treatment for diabetic wounds.

    PubMed

    Heublein, Hannes; Bader, Augustinus; Giri, Shibashish

    2015-06-01

    Diabetic wounds remain a global unsolved problem and the cost of diabetes-related amputations and diabetic wound treatment is approximately US$3 billion and US$9 billion per year, respectively. Diabetic foot ulcers (DFUs) occur in 15% of all patients with diabetes and precede 84% of all diabetes-related lower leg amputations. Currently, there is no satisfying treatment for these hard-to-heal-wounds. However, as we discuss here, experimental preclinical evidence for the successful use of adult stem cell therapies for diabetic wounds gives new hope for the development of effective treatments for use in the clinic. PMID:25603421

  13. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies. PMID:20370314

  14. No evidence of plasticity in hair follicles of recipients after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Rovó, Alicia; Meyer-Monard, Sandrine; Heim, Dominik; Arber, Caroline; Passweg, Jakob R; Gratwohl, Alois; Tichelli, André

    2005-08-01

    Here we show in a prospective quantitative study of 115 patients after allogeneic hematopoietic stem cell transplantation that hair follicles remain exclusively of recipient type despite full whole blood donor-type chimerism. Our data indicate that unmanipulated hematopoietic donor stem cells do not contribute directly to reconstitution even in an organ at highest need for repair. PMID:16038783

  15. Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential

    PubMed Central

    Isakson, M.; de Blacam, C.; Whelan, D.; McArdle, A.; Clover, A. J. P.

    2015-01-01

    Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC), a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review. PMID:26106431

  16. Stem cell glycolipids.

    PubMed

    Yanagisawa, Makoto

    2011-09-01

    Glycolipids are compounds containing one or more monosaccharide residues bound by a glycosidic linkage to a hydrophobic moiety. Because of their expression patterns and the intracellular localization patterns, glycolipids, including stage-specific embryonic antigens (SSEA-3, SSEA-4, and possibly SSEA-1) and gangliosides (e.g., GD3, GD2, and A2B5 antigens), have been used as marker molecules of stem cells. In this review, I will introduce glycolipids expressed in pluripotent stem cells (embryonic stem cells, induced pluripotent stem cells, very small embryonic-like stem cells, amniotic stem cells, and multilineage-differentiating stress enduring cells), multipotent stem cells (neural stem cells, mesenchymal stem cells, fetal liver multipotent progenitor cells, and hematopoietic stem cells), and cancer stem cells (brain cancer stem cells and breast cancer stem cells), and discuss their availability as biomarkers for identifying and isolating stem cells. PMID:21161592

  17. Cell-based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells.

    PubMed

    Monsel, Antoine; Zhu, Ying-Gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W

    2014-11-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver, or brain. Genomic, proteomic, and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of promitotic, antiapoptotic, antiinflammatory, and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, the authors review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. (ANESTHESIOLOGY 2014; 121:1099-121). PMID:25211170

  18. Cell-based Therapy for Acute Organ Injury: Preclinical Evidence and On-going Clinical Trials Using Mesenchymal Stem Cells

    PubMed Central

    Monsel, Antoine; Zhu, Ying-gang; Gennai, Stephane; Hao, Qi; Liu, Jia; Lee, Jae W.

    2014-01-01

    Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver or brain. Genomic, proteomic and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of pro-mitotic, anti-apoptotic, anti-inflammatory and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, we review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use. PMID:25211170

  19. An evidence for adhesion-mediated acquisition of acute myeloid leukemic stem cell-like immaturities

    SciTech Connect

    Funayama, Keiji; Shimane, Miyuki; Nomura, Hitoshi; Asano, Shigetaka

    2010-02-12

    For long-term survival in vitro and in vivo of acute myeloid leukemia cells, their adhesion to bone marrow stromal cells is indispensable. However, it is still unknown if these events are uniquely induced by the leukemic stem cells. Here we show that TF-1 human leukemia cells, once they have formed a cobblestone area by adhering to mouse bone marrow-derived MS-5 cells, can acquire some leukemic stem cell like properties in association with a change in the CD44 isoform-expression pattern and with an increase in a set of related microRNAs. These findings strongly suggest that at least some leukemia cells can acquire leukemic stem cell like properties in an adhesion-mediated stochastic fashion.

  20. Materials as stem cell regulators

    NASA Astrophysics Data System (ADS)

    Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

    2014-06-01

    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.

  1. 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

  2. Transplantation of mesenchymal stem cells for the treatment of liver diseases, is there enough evidence?

    PubMed

    Meier, Raphael P H; Müller, Yannick D; Morel, Philippe; Gonelle-Gispert, Carmen; Bühler, Leo H

    2013-11-01

    Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been extensively investigated in small animal models to treat both acute and chronic liver injuries. Mechanisms of action are not clearly elucidated but may include their ability to differentiate into hepatocyte-like cells, to reduce inflammation, and to enhance tissue repair at the site of injury. This approach is controversial and evidence in large animals is missing. Side effects of MSC infusion such as the contribution to a fibrotic process have been reported in experimental settings. Nevertheless, MSCs moved quickly from bench to bedside and over 280 clinical trials are registered, of which 28 focus on the treatment of liver diseases. If no severe side-effects were observed so far, long-term benefits remain uncertain. More preclinical data regarding mechanisms of action, long term safety and efficacy are warranted before initiating large scale clinical application. The proposal of this review is to visit the current state of knowledge regarding mechanisms behind the therapeutic effects of MSCs in the treatment of experimental liver diseases, to address questions about efficacy and risk, and to discuss recent clinical advances involving MSC-based therapies. PMID:24090934

  3. Slow cycling cells in the continuous dental lamina of Scyliorhinus canicula: new evidence for stem cells in sharks.

    PubMed

    Vandenplas, Sam; Vandeghinste, Robbe; Boutet, Agnes; Mazan, Sylvie; Huysseune, Ann

    2016-05-01

    In the lesser spotted catshark (Scyliorhinus canicula), as in most non-mammalian vertebrates, the dentition renews throughout life. To contribute to our understanding of how continuous tooth replacement is achieved, we searched for evidence for the presence of stem cells in this species. Three-dimensional reconstructions of juvenile (2-3 weeks post-hatch) specimens showed that tooth families merge imperceptibly with so-called interdental zones within a continuous and permanent dental lamina. Interdental regions are composed of three layers, continuous with cervical loop, middle, and outer dental epithelium of the tooth families, respectively. A BrdU pulse-chase experiment revealed that cell proliferation is initiated in the lingual part of the dental lamina and the resulting population shifts one tooth position towards the oral epithelium in around four to five weeks. In the longest chase time (114 days) label-retaining and arguably non-differentiated cells were present at the lingual border of the dental lamina. These were found in the outer and middle dental epithelium, both within and between tooth families. This area of the dental lamina did not show expression or distribution of Sox2. Our data support the hypothesis that stem cells reside at the lingual border of the continuous dental lamina, more specifically in the middle dental epithelium at the level of the tooth families, and in its extension between the tooth families. To demonstrate their true stemness and their role in continuous tooth replacement, it remains to be shown that these cells have the potential to give rise to a complete new successor. PMID:26988117

  4. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth. PMID:14521517

  5. Stem cells and cardiovascular disease.

    PubMed

    Abbott, J Dawn; Giordano, Frank J

    2003-01-01

    Several recent discoveries have shifted the paradigm that there is no potential for myocardial regeneration and have fueled enthusiasm for a new frontier in the treatment of cardiovascular disease-stem cells. Fundamental to this emerging field is the cumulative evidence that adult bone marrow stem cells can differentiate into a wide variety of cell types, including cardiac myocytes and endothelial cells. This phenomenon has been termed stem cell plasticity and is the basis for the explosive recent interest in stem cell-based therapies. Directed to cardiovascular disease, stem cell therapy holds the promise of replacing lost heart muscle and enhancing cardiovascular revascularization. Early evidence of the feasibility of stem cell therapy for cardiovascular disease came from a series of animal experiments demonstrating that adult stem cells could become cardiac muscle cells (myogenesis) and participate in the formation of new blood vessels (angiogenesis and vasculogenesis) in the heart after myocardial infarction. These findings have been rapidly translated to ongoing human trials, but many questions remain. This review focuses on the use of adult bone marrow-derived stem cells for the treatment of ischemic cardiovascular disease and will contrast how far we have come in a short time with how far we still need to go before stem cell therapy becomes routine in cardiovascular medicine. PMID:12900745

  6. Experimental myocardial stem cell therapy for ST-elevation myocardial infarction: rationale and level of evidence.

    PubMed

    Kastrup, Jens; Mygind, Naja D; Qayyum, Abbas A; Mathiasen, Anders B

    2016-06-01

    Ischemic heart disease (IHD) is one of the leading causes of death worldwide and is characterized by the formation of atherosclerotic plaques in the coronary arteries reducing the blood supply to the heart muscle causing ischemia. IHD can result in ST-elevation myocardial infarction (STEMI), chronic IHD and heart failure. The patients suffer from chest pain (angina), dyspnea and a reduced quality of life. Common for all these conditions is loss of functional cardiomyocytes and endothelial cells. Stem cell therapy to regenerate injured myocardium is a new treatment option which has gained much interest in the last 10-15 years especially after STEMI. Many preclinical and clinical studies have shown encouraging results but also very diverse clinical outcomes after stem cell treatment. This diversity in results may be explained by different factors, such as cell isolation technique, infarct location, timing and route of delivery, cell dosage, cell type etc. The present review will try to elaborate and clarify the present status for stem cell therapy in STEMI. PMID:26899403

  7. Stem cells supporting other stem cells

    PubMed Central

    Leatherman, Judith

    2013-01-01

    Adult stem cell therapies are increasingly prevalent for the treatment of damaged or diseased tissues, but most of the improvements observed to date are attributed to the ability of stem cells to produce paracrine factors that have a trophic effect on existing tissue cells, improving their functional capacity. It is now clear that this ability to produce trophic factors is a normal and necessary function for some stem cell populations. In vivo adult stem cells are thought to self-renew due to local signals from the microenvironment where they live, the niche. Several niches have now been identified which harbor multiple stem cell populations. In three of these niches – the Drosophila testis, the bulge of the mammalian hair follicle, and the mammalian bone marrow – one type of stem cell has been found to produce factors that contribute to the maintenance of a second stem cell population in the shared niche. In this review, I will examine the architecture of these three niches and discuss the molecular signals involved. Together, these examples establish a new paradigm for stem cell behavior, that stem cells can promote the maintenance of other stem cells. PMID:24348512

  8. 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. PMID:20560026

  9. Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties.

    PubMed

    Huang, Xiaoxing; Xiong, Meng; Jin, Yujie; Deng, Chaohua; Xu, Hui; An, Changqing; Hao, Ling; Yang, Xiangyong; Deng, Xinzhou; Tu, Zhenbo; Li, Xinran; Xiao, Ruijing; Zhang, Qiuping

    2016-07-01

    Leukemia represents a spectrum of hematological malignancies threatening human health. Resistance to treatments and metastasis of leukemia are the main causes of death in patients. Leukemia stem cells (LSCs) are the initiating cells of leukemia as well as the main source of drug resistance, invasion and metastasis. Consequently, eliminating LSCs is a prerequisite to eradicate leukemia. Preliminary studies in our laboratory have shown that chemokines and their related receptors play an important role in the drug resistance and metastasis of leukemic cells. In this study, we obtained high migration drug-surviving (short term) MOLT4 cells (hMDSCs-MOLT4) with treatment of doxorubicin (DOX) after Transwell assay. Then we detected stem cell-associated molecular markers on hMDSCs-MOLT4 cells and the parental MOLT4 cells by FCM, QPCR, western blotting, H&E staining and immunohisto-chemistry experimental techniques in vitro and in vivo. Moreover, we explored its impact on drug resistance and tumor formation. Then we found that compared with the parental MOLT4 cells, the mRNA expression levels of stem cell-related factors Sox2, Oct4, C-myc, Klf4, Nanog, Bmi-1, CXCR4 are increased in hMDSCs-MOLT4 cells, together with the protein expression levels of Sox2, Oct4, Klf4, Nanog, CXCR4 and CD34. Our results indicated that hMDSCs-MOLT4 cells exhibited strong drug resistance and certain cancer stem cell-like characteristics. It is the first indication that the targeting stemness factors such as Sox2, Oct4, Klf4, Nanog and CXCR4 may represent plausible options for eliminating T-ALL stem-like cells. The present findings shed light on the relationship between drug-tolerant leukemic cells and cancer stem cells. PMID:27210806

  10. Alveolar epithelial stem and progenitor cells: emerging evidence for their role in lung regeneration.

    PubMed

    Hoffman, A M; Ingenito, E P

    2012-01-01

    Lung injuries that impact the alveolus, such as emphysema, pulmonary fibrosis, and acute lung injury, are costly and prevalent problems. Moreover, the extent of alveolar injury and impairment of gas exchange is strongly associated with prognosis and survival. Thus, mechanisms of repair and regeneration of the lung alveolar compartment have received mounting attention as newer approaches to the study of stem and progenitor cells in this region unfold. The role of type II alveolar epithelial as the sole source of type I (AECI) and II (AECII) alveolar epithelial cells following lung injury has been recently challenged; recently, investigators have described stemprogenitor cells that function like precursors to AECII either in vitro or in vivo, both in mice and humans. Techniques to explore selfrenewal and multipotency have been rigorously applied to these putative stem-progenitor cell populations and the data thus far is compelling. This review provides background to the study of alveolar regeneration with the aim to provide context to the recent discoveries of putative stem-progenitor cells that may contribute to this process. PMID:23016551

  11. Why do stem cells exist?

    PubMed

    Heddle, J A; Cosentino, L; Dawod, G; Swiger, R R; Paashuis-Lew, Y

    1996-01-01

    Self-renewing tissues have a differentiation hierarchy such that the stem cells are the only permanent residents of the tissue, and it is in these cells that most cancerous mutations arise. The progeny of the stem cells either remain stem cells or enter a transient proliferating cell population that differentiates to produce the functional cells of the tissue. The reason that this differentiation hierarchy exists has not been established. We show here that alternative hierarchies, in which there would be no stem cells, are feasible and biologically plausible. We show that current evidence from somatic mutation frequencies at both transgenic and endogenous loci implicates cell division in the origin of most somatic mutations. We suggest, therefore, that the existence of stem cells is an evolutionary consequence of a selective pressure to avoid cancer by reducing the number of somatic mutations. The stem cell hierarchy reduces the number of cell divisions of those cells that reside permanently in the tissue, which reduces the number of somatic mutations and thus minimizes the cancer rate. In the small intestine, the existence of stem cells reduces the mutant frequency in the stem cells by about one order of magnitude. Since two or more mutations are required to transform a cell, the protective effect may be 100-fold or more. Similar factors may be expected in other tissues. PMID:8991061

  12. Evidence for AKT-independent regulation of FOXO1 and FOXO3 in haematopoietic stem and progenitor cells.

    PubMed

    Liang, Raymond; Rimmelé, Pauline; Bigarella, Carolina L; Yalcin, Safak; Ghaffari, Saghi

    2016-03-18

    Transcription factors FOXOs (1, 3, 4) are essential for the maintenance of haematopoietic stem cells. FOXOs are evolutionary conserved substrates of the AKT serine threonine protein kinase that are also phosphorylated by several kinases other than AKT. Specifically, phosphorylation by AKT is known to result in the cytosolic localization of FOXO and subsequent inhibition of FOXO transcriptional activity. In addition to phosphorylation, FOXOs are regulated by a number of other post-translational modifications including acetylation, methylation, redox modulation, and ubiquitination that altogether determine these factors' output. Cumulating evidence raises the possibility that in stem cells, including in haematopoietic stem cells, AKT may not be the dominant regulator of FOXO. To address this question in more detail, we examined gene expression, subcellular localization, and response to AKT inhibition of FOXO1 and FOXO3, the main FOXO expressed in HSPCs (haematopoietic stem and progenitor cells). Here we show that while FOXO1 and FOXO3 transcripts are expressed at similar levels, endogenous FOXO3 protein is mostly nuclear compared to the cytoplasmic localization of FOXO1 in HSPCs. Furthermore, inhibition of AKT does not enhance nuclear localization of FOXO1 nor FOXO3. Nonetheless AKT inhibition in the context of loss of NAD-dependent SIRT1 deacetylase modulates FOXO3 localization in HSPCs. Together, these data suggest that FOXO3 is more active than FOXO1 in primitive haematopoietic stem and multipotent progenitor cells. In addition, they indicate that upstream regulators other than AKT, such as SIRT1, maintain nuclear FOXO localization and activity in HSPCs. PMID:26929388

  13. Embryonic hematopoietic stem cells and interstitial Cajal cells in the hindgut of late stage human embryos: evidence and hypotheses.

    PubMed

    Ilie, C A; Rusu, M C; Didilescu, A C; Motoc, A G M; Mogoantă, L

    2015-07-01

    There have been few studies on human embryos describing a specific pattern of hindgut colonization by hematopoietic stem cells (HSCs) and interstitial Cajal cells (ICCs). We aimed to study CD34, CD45 and CD117/c-kit expression in late stage human embryos, to attain observational data that could be related to studies on the aorta-gonad-mesonephros (AGM)-derived HSCs, and data on hindgut ICCs. Antibodies were also applied to identify alpha-smooth muscle actin and neurofilaments. Six human embryos of 48-56 days were used. In the 48 day embryo, the hindgut was sporadically populated by c-kit+ ICCs, but, in all other embryos, a layer of myenteric ICCs had been established. Intraneural c-kit+ cells were found in pelvic nerves and vagal trunks, suggesting that the theory of Ramon y Cajal assuming that ICCs may be primitive neurons may not be so invalid. Also in the 48 day embryo, c-kit+/CD45+ perivascular cells were found along the pelvic neurovascular axes, suggesting that not only liver, but also other organs could be seeded with HSCs from the AGM region. CD45+ cells with dendritic morphologies were found in all hindgut layers, including the epithelium. This last evidence is suggestive of an AGM contribution to the tissue resident macrophages and could be related to processes of sprouting angiogenesis which, in turn, have been found to be guided by filopodia of endothelial tip cells. Further studies on human embryonic and fetal material should be performed to attempt to clarify whether the hindgut colonization with HSCs is a transitory or definitive process. PMID:25723517

  14. Pathological Left Ventricular Hypertrophy and Stem Cells: Current Evidence and New Perspectives

    PubMed Central

    Marketou, Maria E.; Parthenakis, Fragiskos; Vardas, Panos E.

    2016-01-01

    Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes. It is the result of complex mechanisms that include not only an increase in protein synthesis and cell size but also proliferating cardiac progenitor cells and the influx of bone marrow-derived cells developing into cardiomyocytes. Stem and progenitor cells are known to contribute to the renewal of adult mammalian cardiomyocytes in case of myocardial injury or pressure and volume overload. They are activated in LVH and play a regulatory role in myocardial repair. They have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs that play important roles in cell differentiation, cardiac remodeling, and neovascularization. They are mobilized in response to either mechanical or chemical stimuli, hormones, or pharmacologic agents. Another important source of progenitor cells is the epicardial layer. It appears that precursor cells migrate from the epicardium to the myocardium in order to interact with myocardial cells. In addition, migratory cells participate in the formation of almost all cardiac structures in myocardial hypertrophy. Although the pathophysiological mechanisms are still obscure and further studies are required, their properties may open the door to regenerative cell therapy for the prevention of adverse remodeling. PMID:26798360

  15. Short communication: Initial evidence supporting existence of potential rumen epidermal stem and progenitor cells.

    PubMed

    Yohe, T T; Tucker, H L M; Parsons, C L M; Geiger, A J; Akers, R M; Daniels, K M

    2016-09-01

    The bovine rumen epidermis is a keratinized multilayered tissue that experiences persistent cell turnover. Because of this constant cell turnover, epidermal stem cells and their slightly more differentiated daughter cells, epidermal progenitor cells, must exist in the stratum basale of rumen epidermis. To date, these 2 epidermal cell populations and any unique cellular markers they may possess remain completely uncharacterized in the bovine rumen. An important first step in this new research area is the demonstration of the relative abundance and existence of markers for these cells in rumen tissue. A related second step is to document rumen epidermal proliferative responses to an extrinsic signal such as nutrient concentration within the rumen. The objectives of this experiment were to evaluate the extrinsic effect of diet on (1) gene expression of 6 potential rumen epidermal stem or progenitor cell markers and (2) rumen epidermal cell proliferation within the stratum basale. Twelve preweaned Holstein heifers were fed either a restricted diet (R) or an enhanced diet (EH). Animals on R received a milk replacer (MR) diet fed at 0.44kg of powder dry matter (DM)/d (20.9% crude protein, 29.8% fat, DM basis) and EH received MR at 1.08kg of powder dry matter/d (28.9% crude protein, 26.2% fat, DM basis). All calves had access to a 20% crude protein starter and were weaned during wk 7 of the experiment. Lifetime DM intake was 0.73kg of DM/calf per day for R (5.88 Mcal of net energy/calf per day) and 1.26kg of DM/calf per day for EH (10.68 Mcal of net energy/calf per day). Twenty-four hours before slaughter heifers received an intravenous dose of 5-bromo-2'-deoxyuridine to label proliferating cells. Heifers were slaughtered at 8 wk of age, and rumen samples from the ventral sac region were obtained and stored in RNA preservative and processed for routine histology. Quantitative real-time reverse transcriptase PCR was used to analyze relative abundance of genes. Candidate

  16. Stem Cell Research.

    PubMed

    Trounson, Alan; Kolaja, Kyle; Petersen, Thomas; Weber, Klaus; McVean, Maralee; Funk, Kathleen A

    2015-01-01

    Stem cells have great potential in basic research and are being slowly integrated into toxicological research. This symposium provided an overview of the state of the field, stem cell models, described allogenic stem cell treatments and issues of immunogenicity associated with protein therapeutics, and tehn concentrated on stem cell uses in regenerative medicine focusing on lung and testing strategies on engineered tissues from a pathologist's perspective. PMID:25899720

  17. Information on Stem Cell Research

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS Information on Stem Cell Research Research @ NINDS Stem Cell Highlights Submit a hESC ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of NINDS ...

  18. Biochanin A Promotes Osteogenic but Inhibits Adipogenic Differentiation: Evidence with Primary Adipose-Derived Stem Cells

    PubMed Central

    Su, Shu-Jem; Su, Shu-Hui; Shyu, Huey-Wen; Chen, Kuan-Ming; Yeh, Hua

    2013-01-01

    Biochanin A has promising effects on bone formation in vivo, although the underlying mechanism remains unclear yet. This study therefore aimed to investigate whether biochanin A regulates osteogenic and adipogenic differentiation using primary adipose-derived stem cells. The effects of biochanin A (at a physiologically relevant concentration of 0.1–1 μM) were assessed in vitro using various approaches, including Oil red O staining, Nile red staining, alizarin red S staining, alkaline phosphatase (ALP) activity, flow cytometry, RT-PCR, and western blotting. The results showed that biochanin A significantly suppressed adipocyte differentiation, as demonstrated by the inhibition of cytoplasmic lipid droplet accumulation, along with the inhibition of peroxisome proliferator-activated receptor gamma (PPARγ), lipoprotein lipase (LPL), and leptin and osteopontin (OPN) mRNA expression, in a dose-dependent manner. On the other hand, treatment of cells with 0.3 μM biochanin A increased the mineralization and ALP activity, and stimulated the expression of the osteogenic marker genes ALP and osteocalcin (OCN). Furthermore, biochanin A induced the expression of runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), and Ras homolog gene family, member A (RhoA) proteins. These observations suggest that biochanin A prevents adipogenesis, enhances osteoblast differentiation in mesenchymal stem cells, and has beneficial regulatory effects in bone formation. PMID:23843885

  19. Evidence that osteogenic progenitor cells in the human tunica albuginea may originate from stem cells: implications for peyronie disease.

    PubMed

    Vernet, Dolores; Nolazco, Gaby; Cantini, Liliana; Magee, Thomas R; Qian, Ansha; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F

    2005-12-01

    Tissue ossification in Peyronie disease (commonly known as Peyronie's disease [PD]), a localized fibrotic lesion within the tunica albuginea (TA) of the penis, may result from osteogenic differentiation of fibroblasts, myofibroblasts, and/or adult stem cells in the TA, and may be triggered by chronic inflammation, oxidative stress, and profibrotic factors like transforming growth factor beta 1 (TGFB1). In this study, we have investigated whether cultures of cells from normal TA and PD plaques undergo osteogenesis, express markers for stem cells, and originate other cell lineages via processes modulated by TGFB1. We found that TA and PD cells in osteogenic medium (OM) expressed osteogenic markers, alkaline phosphatase, and osteopontin and underwent calcification. PD cells, but not TA cells, formed foci in soft agar that were positive for alkaline phosphatase and calcification and expressed the mRNAs for osteoblast-specific factors pleiotrophin and periostin and bone morphogenic protein 2. Both cultures expressed stem cell marker CD34 antigen but not protein tyrosine phosphatase, receptor type c. TA and PD cells expressed smooth-muscle cell markers smoothelin and transgelin. None of the cultures underwent adipogenesis in adipogenic medium. Incubation with TGFB1 increased osteogenesis and myofibroblast differentiation and reduced CD34 antigen expression in both cultures. TA and PD cells modulated the differentiation of the multipotent C3H 10T(1/2) cells in dual cultures, into osteoblasts and myofibroblasts. In conclusion, both TA and PD cultures contain cells, presumably stem cells, that undergo osteogenic and myofibroblast differentiation, and may induce these processes by paracrine interactions. This may explain progression of fibrosis in the PD plaque and its eventual calcification. PMID:16093362

  20. 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. PMID:22404469

  1. Toward 'SMART' stem cells.

    PubMed

    Cheng, T

    2008-01-01

    Stem cell research is at the heart of regenerative medicine, which holds great promise for the treatment of many devastating disorders. However, in addition to hurdles posed by well-publicized ethical issues, this emerging field presents many biological challenges. What is a stem cell? How are embryonic stem cells different from adult stem cells? What are the physiological bases for therapeutically acceptable stem cells? In this editorial review, I will briefly discuss these superficially simple but actually rather complex issues that surround this fascinating cell type. The goal of this special issue on stem cells in Gene Therapy is to review some fundamental and critical aspects of current stem cell research that have translational potential. PMID:18046429

  2. Stem Cell Information: Glossary

    MedlinePlus

    ... based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed ... Pluripotent Polar body Preimplantation Proliferation Regenerative medicine Reproductive cloning Signals Somatic cell Somatic cell nuclear transfer (SCNT) ...

  3. Between hope and evidence: how community advisors demarcate the boundary between legitimate and illegitimate stem cell treatments.

    PubMed

    Petersen, Alan; Tanner, Claire; Munsie, Megan

    2015-03-01

    Stem cell science provides an exemplary study of the 'management of hope'. On the one hand, raising 'hopes' and expectations is a seen as a necessary aspect of securing investment in promising innovative research. On the other, such hyperbole risks raising hopes to a level that may lead people to undertake undue risks, which may ultimately undermine confidence in medical research. In this context, the 'management of hope' thus involves the negotiation of competing claims of truth about the value and safety of particular treatments and about the trustworthiness of providers. Using Gieryn's concept of boundary-work, this article examines the means by which this work of 'managing hope' is undertaken. Drawing on data collected as part of our study that investigated the perspectives of those who are consulted by patients and their carers about stem cell treatments, we explore how these community advisors – both scientists and clinicians with a stake in stem cell research and representatives from patient advocacy groups – demarcate the boundary between legitimate and illegitimate treatments. In particular, we examine how these actors rhetorically use 'evidence' to achieve this demarcation. We argue that analysing accounts of how advisors respond to patient enquiries about stem cell treatments offers a window for examining the workings of the politics of hope within contemporary bioscience and biomedicine. In conclusion, we emphasize the need to re-conceptualize the boundary between science and non-science so as to allow a better appreciation of the realities of health care in the age of medical travel. PMID:25367895

  4. Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas

    PubMed Central

    Aboody, Karen S.; Brown, Alice; Rainov, Nikolai G.; Bower, Kate A.; Liu, Shaoxiong; Yang, Wendy; Small, Juan E.; Herrlinger, Ulrich; Ourednik, Vaclav; Black, Peter McL.; Breakefield, Xandra O.; Snyder, Evan Y.

    2000-01-01

    One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them “elusive” to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extensively throughout the tumor bed and migrate uniquely in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to stably express a foreign gene. The NSCs “surround” the invading tumor border while “chasing down” infiltrating tumor cells. When implanted intracranially at distant sites from the tumor (e.g., into normal tissue, into the contralateral hemisphere, or into the cerebral ventricles), the donor cells migrate through normal tissue targeting the tumor cells (including human glioblastomas). When implanted outside the CNS intravascularly, NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecule—cytosine deaminase—such that quantifiable reduction in tumor burden results. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory, migratory, invasive brain tumors. More broadly, they suggest that NSC migration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present. PMID:11070094

  5. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts.

    PubMed

    Lama, Vibha N; Smith, Lisa; Badri, Linda; Flint, Andrew; Andrei, Adin-Cristian; Murray, Susan; Wang, Zhuo; Liao, Hui; Toews, Galen B; Krebsbach, Paul H; Peters-Golden, Marc; Pinsky, David J; Martinez, Fernando J; Thannickal, Victor J

    2007-04-01

    The origin and turnover of connective tissue cells in adult human organs, including the lung, are not well understood. Here, studies of cells derived from human lung allografts demonstrate the presence of a multipotent mesenchymal cell population, which is locally resident in the human adult lung and has extended life span in vivo. Examination of plastic-adherent cell populations in bronchoalveolar lavage samples obtained from 76 human lung transplant recipients revealed clonal proliferation of fibroblast-like cells in 62% (106 of 172) of samples. Immunophenotyping of these isolated cells demonstrated expression of vimentin and prolyl-4-hydroxylase, indicating a mesenchymal phenotype. Multiparametric flow cytometric analyses revealed expression of cell-surface proteins, CD73, CD90, and CD105, commonly found on mesenchymal stem cells (MSCs). Hematopoietic lineage markers CD14, CD34, and CD45 were absent. Multipotency of these cells was demonstrated by their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. Cytogenetic analysis of cells from 7 sex-mismatched lung transplant recipients harvested up to 11 years after transplant revealed that 97.2% +/- 2.1% expressed the sex genotype of the donor. The presence of MSCs of donor sex identity in lung allografts even years after transplantation provides what we believe to be the first evidence for connective tissue cell progenitors that reside locally within a postnatal, nonhematopoietic organ. PMID:17347686

  6. Optimizing stem cell culture.

    PubMed

    van der Sanden, Boudewijn; Dhobb, Mehdi; Berger, François; Wion, Didier

    2010-11-01

    Stem cells always balance between self-renewal and differentiation. Hence, stem cell culture parameters are critical and need to be continuously refined according to progress in our stem cell biology understanding and the latest technological developments. In the past few years, major efforts have been made to define more precisely the medium composition in which stem cells grow or differentiate. This led to the progressive replacement of ill-defined additives such as serum or feeder cell layers by recombinant cytokines or growth factors. Another example is the control of the oxygen pressure. For many years cell cultures have been done under atmospheric oxygen pressure which is much higher than the one experienced by stem cells in vivo. A consequence of cell metabolism is that cell culture conditions are constantly changing. Therefore, the development of high sensitive monitoring processes and control algorithms is required for ensuring cell culture medium homeostasis. Stem cells also sense the physical constraints of their microenvironment. Rigidity, stiffness, and geometry of the culture substrate influence stem cell fate. Hence, nanotopography is probably as important as medium formulation in the optimization of stem cell culture conditions. Recent advances include the development of synthetic bioinformative substrates designed at the micro- and nanoscale level. On going research in many different fields including stem cell biology, nanotechnology, and bioengineering suggest that our current way to culture cells in Petri dish or flasks will soon be outdated as flying across the Atlantic Ocean in the Lindbergh's plane. PMID:20803548

  7. Limbal Stem Cell Transplantation

    PubMed Central

    2008-01-01

    Executive Summary Objective The objective of this analysis is to systematically review limbal stem cell transplantation (LSCT) for the treatment of patients with limbal stem cell deficiency (LSCD). This evidence-based analysis reviews LSCT as a primary treatment for nonpterygium LSCD conditions, and LSCT as an adjuvant therapy to excision for the treatment of pterygium. Background Clinical Need: Condition and Target Population The outer surface of the eye is covered by 2 distinct cell layers: the corneal epithelial layer that overlies the cornea, and the conjunctival epithelial layer that overlies the sclera. These cell types are separated by a transitional zone known as the limbus. The corneal epithelial cells are renewed every 3 to 10 days by a population of stem cells located in the limbus. Nonpterygium Limbal Stem Cell Deficiency When the limbal stem cells are depleted or destroyed, LSCD develops. In LSCD, the conjunctival epithelium migrates onto the cornea (a process called conjunctivalization), resulting in a thickened, irregular, unstable corneal surface that is prone to defects, ulceration, corneal scarring, vascularization, and opacity. Patients experience symptoms including severe irritation, discomfort, photophobia, tearing, blepharospasm, chronic inflammation and redness, and severely decreased vision. Depending on the degree of limbal stem cell loss, LSCD may be total (diffuse) or partial (local). In total LSCD, the limbal stem cell population is completed destroyed and conjunctival epithelium covers the entire cornea. In partial LSCD, some areas of the limbus are unharmed, and the corresponding areas on the cornea maintain phenotypically normal corneal epithelium. Confirmation of the presence of conjunctivalization is necessary for LSCD diagnosis as the other characteristics and symptoms are nonspecific and indicate a variety of diseases. The definitive test for LSCD is impression cytology, which detects the presence of conjunctival epithelium and

  8. Targeting Breast Cancer Stem Cells

    PubMed Central

    Liu, Suling; Wicha, Max S.

    2010-01-01

    There is increasing evidence that many cancers, including breast cancer, contain populations of cells that display stem-cell properties. These breast cancer stem cells, by virtue of their relative resistance to radiation and cytotoxic chemotherapy, may contribute to treatment resistance and relapse. The elucidation of pathways that regulate these cells has led to the identification of potential therapeutic targets. A number of agents capable of targeting breast cancer stem cells in preclinical models are currently entering clinical trials. Assessment of the efficacy of the agents will require development of innovative clinical trial designs with appropriate biologic and clinical end points. The effective targeting of breast cancer stem cells has the potential to significantly improve outcome for women with both early-stage and advanced breast cancer. PMID:20498387

  9. Evidence for Epithelial-Mesenchymal Transition in Cancer Stem Cells of Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Chen, Chao; Wei, Yan; Hummel, Michael; Hoffmann, Thomas K.; Gross, Manfred; Kaufmann, Andreas M.; Albers, Andreas E.

    2011-01-01

    Initiation, growth, recurrence, and metastasis of head and neck squamous cell carcinomas (HNSCC) have been related to the behavior of cancer stem cells (CSC) that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. We quantified and enriched ALDH1+ cells within HNSCC cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT). Spheroid culture enriched CSC from five HNSCC cell lines by up to 5-fold. In spheroid-derived cells (SDC) and the parental monolayer-derived cell line ALDH1, CD44, CD24, E-Cadherin, α-SMA, and Vimentin expression was compared by flow-cytometry and immunofluorescence together with proliferation and cell cycle analysis. Invasion activity was evaluated by Matrigel assay and expression of stemness-related transcription factors (TF) Nanog, Oct3/4, Sox2 and EMT-related genes Snail1 and 2, and Twist by real-time PCR. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in SDC. ALDH1+ cells showed increased colony-formation. The proportion of cells with a putative CSC marker constellation of CD44+/CD24− was highly variable (0.5% to 96%) in monolayer and spheroid cultures and overlapped in 0%–33% with the CD44+/CD24−/ALDH1+ cell subset. SDC had significantly higher invading activity. mRNA of the stemness-related genes Sox2, Nanog, and Oct3/4 was significantly increased in SDC of all cell lines. Twist was significantly increased in two while Snail2 showed a significant increase in one and a significant decrease in SDC of two cell lines. SDC had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. HNSCC-lines harbor potential CSC, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSC can be enriched by

  10. Stress and stem cells.

    PubMed

    Tower, John

    2012-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress. PMID:23799624

  11. Dental stem cell patents.

    PubMed

    Morsczeck, Christian; Frerich, Bernhard; Driemel, Oliver

    2009-01-01

    A complex human tissue harbors stem cells that are responsible for its maintenance or repair. These stem cells have been isolated also from dental tissues such as the periodontal ligament, dental papilla or dental follicle and they may offer novel applications in dentistry. This following review summarizes patents about dental stem cells for dental tissue engineering and considers their value for regenerative dentistry. PMID:19149737

  12. 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. PMID:23417722

  13. Intraoperative Stem Cell Therapy

    PubMed Central

    Coelho, Mónica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

    2013-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  14. Stem Cell Treatment of the Heart

    PubMed Central

    Angelini, Paolo; Markwald, Roger R.

    2005-01-01

    Stem cells are multipotent, undifferentiated cells capable of multiplication and differentiation. Preliminary experimental evidence suggests that stem cells derived from embryonic or adult tissues (especially bone marrow) may develop into myocardial cells. Some experts believe that this phenomenon occurs naturally in human beings, specifically during recovery from a myocardial infarction. Recently, stem cells have been used with the therapeutic intention of regenerating damaged tissues. Cardiac experiments, mainly with adult homologous stem cells, have proved that this therapy is safe and may improve myocardial vascularization and pump function. We review current fundamental concepts regarding the normal development of embryonic stem cells into myocardial tissue and the heart as a whole. We describe the multiple conditions that naturally enable a stem cell to become a myocardial cell and a group of stem cells to become a heart. We also discuss the challenge of translating basic cellular and molecular mechanisms into effective, clinically relevant treatment options. PMID:16429891

  15. The leukemic stem cell

    PubMed Central

    Jordan, Craig T.

    2007-01-01

    Malignant stem cells have recently been described as the source of several types of human cancer. These unique cell types are typically rare and possess properties that are distinct from most other tumor cells. The properties of leukemic stem cells indicate that current chemotherapy drugs will not be effective. The use of current cytotoxic agents is not effective in leukemia because the agents target both the leukemic and normal stem cell populations. Consequently, new strategies are required that specifically and preferentially target the malignant stem cell population, while sparing normal stem cells. Several well known agents are lethal for the leukemic stem cell in preclinical testing. They include parthenolide, commonly known as feverfew, and TDZD-8. They have undergone various levels of preclinical development, but have not been used in patients as yet in the cancer setting. These drugs and combinations of existing therapies that target the leukemic stem cell population may provide a cure in this disease. This article summarizes recent findings in the leukemic stem cell field and discusses new directions for therapy. PMID:17336250

  16. Stem Cell Separation Technologies

    PubMed Central

    Zhu, Beili; Murthy, Shashi K.

    2012-01-01

    Stem cell therapy and translational stem cell research require large-scale supply of stem cells at high purity and viability, thus leading to the development of stem cell separation technologies. This review covers key technologies being applied to stem cell separation, and also highlights exciting new approaches in this field. First, we will cover conventional separation methods that are commercially available and have been widely adapted. These methods include Fluorescence-activated cell sorting (FACS), Magnet-activated cell sorting (MACS), pre-plating, conditioned expansion media, density gradient centrifugation, field flow fractionation (FFF), and dielectrophoresis (DEP). Next, we will introduce emerging novel methods that are currently under development. These methods include improved aqueous two-phase system, systematic evolution of ligands by exponential enrichment (SELEX), and various types of microfluidic platforms. Finally, we will discuss the challenges and directions towards future breakthroughs for stem cell isolation. Advancing stem cell separation techniques will be essential for clinical and research applications of stem cells. PMID:23505616

  17. Epigenetic Regulation of Mammalian Stem Cells

    PubMed Central

    Li, Xuekun

    2008-01-01

    Two critical properties of stem cells are self-renewal and multipotency. The maintenance of their “stemness” state and commitment to differentiation are therefore tightly controlled by intricate molecular networks. Epigenetic mechanisms, including DNA methylation, chromatin remodeling and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. Recent studies have shown that epigenetic regulators are key players in stem cell biology and their dysfunction can result in human diseases such as cancer and neurodevelopmental disorders. Here, we review the recent evidences that advance our knowledge in epigenetic regulations of mammalian stem cells, with focus on embryonic stem cells and neural stem cells. PMID:18393635

  18. Stem cells in dermatology*

    PubMed Central

    Ogliari, Karolyn Sassi; Marinowic, Daniel; Brum, Dario Eduardo; Loth, Fabrizio

    2014-01-01

    Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today. PMID:24770506

  19. 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

  20. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  1. Hematopoietic stem cell transplantation

    PubMed Central

    Hatzimichael, Eleftheria; Tuthill, Mark

    2010-01-01

    More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes. Before transplantation, patients receive intensive myeloablative chemoradiotherapy followed by stem cell “rescue.” Autologous HSCT is performed using the patient’s own hematopoietic stem cells, which are harvested before transplantation and reinfused after myeloablation. Allogeneic HSCT uses human leukocyte antigen (HLA)-matched stem cells derived from a donor. Survival after allogeneic transplantation depends on donor–recipient matching, the graft-versus-host response, and the development of a graft versus leukemia effect. This article reviews the biology of stem cells, clinical efficacy of HSCT, transplantation procedures, and potential complications. PMID:24198516

  2. Evidence of the Survival of Ectopically Transplanted Oral Mucosal Epithelial Stem Cells After Repeated Wounding of Cornea

    PubMed Central

    Sugiyama, Hiroaki; Yamato, Masayuki; Nishida, Kohji; Okano, Teruo

    2014-01-01

    Tissue engineering has become an essential tool in the development of regenerative medicine. We have developed cell sheet–based techniques for use in regenerative medicine that have already been successfully used in clinical applications. Native corneal epithelium is produced from limbal stem cells located in the transition zone between the cornea and the bulbar conjunctiva. Limbal stem cell deficiency (LSCD) is a severe defect of the limbal stem cells leading to vision loss due to conjunctival epithelial invasion and neovascularization. Rabbit LSCD models were treated with transplantable autologous oral mucosal epithelial cell (OEC) sheets fabricated on temperature-responsive cell culture surfaces, after which, the ocular surfaces were clear and smooth with no observable defects. The central part of the reconstructed ocular surface was scraped and wounded, after which proliferating epithelial cells covered the scraped area within a few days. The ocular surfaces were clear and smooth even after repeated scrapings and consisted of only OECs or heterogeneously mixed with corneal epithelial cells. This study demonstrates that transplanted cell sheets containing oral mucosal epithelial stem cells could reconstruct the ocular surface to maintain cornea homeostasis; moreover, they provide an ideal microenvironment to support the proliferation of remaining native limbal stem cells. PMID:24769908

  3. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  4. Evidence for a subventricular zone neural stem cell phagocytic activity stimulated by the vitamin K-dependent factor protein S.

    PubMed

    Ginisty, Aurélie; Gély-Pernot, Aurore; Abaamrane, Loubna; Morel, Franck; Arnault, Patricia; Coronas, Valérie; Benzakour, Omar

    2015-02-01

    Neural stem cells, whose major reservoir in the adult mammalian brain is the subventricular zone (SVZ), ensure neuropoiesis, a process during which many generated cells die. Removal of dead cells and debris by phagocytes is necessary for tissue homeostasis. Using confocal and electron microscopy, we demonstrate that cultured SVZ cells phagocytose both 1 and 2 µm latex beads and apoptotic cell-derived fragments. We determine by flow cytometry that phagocytic cells represent more than 10% of SVZ cultured cells. Phenotyping of SVZ cells using nestin, GFAP, Sox2, or LeX/SSEA and quantification of aldehyde dehydrogenase (ALDH) activity, reveals that cells with neural stem-cell features phagocytose and represent more than 30% of SVZ phagocytic cells. In vivo, nestin-, Sox2-, and ALDH-expressing neural stem-like cells engulfed latex beads or apoptotic cell-derived fragments that were injected into mice lateral brain ventricles. We show also that SVZ cell phagocytic activity is an active process, which depends both on cytoskeleton dynamic and on recognition of phosphatidylserine eat-me signal, and is stimulated by the vitamin K-dependent factor protein S (ProS). ProS neutralizing antibodies inhibit SVZ cell phagocytic activity and exposure of SVZ cells to apoptotic cell-derived fragments induces a transient Mer tyrosine kinase receptor (MerTK) phosphorylation. Conversely, MerTK blocking antibodies impair both basal and ProS-stimulated SVZ cell phagocytic activity. By revealing that neural stem-like cells act within the SVZ neurogenic niche as phagocytes and that the ProS/MerTK path represents an endogenous regulatory mechanism for SVZ cell phagocytic activity, the present report opens-up new perspectives for both stem cell biology and brain physiopathology. PMID:25308179

  5. Mesenchymal stem cells.

    PubMed

    Ding, Dah-Ching; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2011-01-01

    Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases. PMID:21396235

  6. Efficacy of hematopoietic stem cell formultiple sclerosis, an evidence based meta-analysis.

    PubMed

    Li, C; Feng, J; Chen, S; He, Y

    2016-01-01

    Multiple sclerosis (MS) is thought to be a serious autoimmune disease. However, few therapy method was efficient for MS. The hematopoietic cell transplant (HCT) has been reported for a long time and can be used for MS. The clinical trials consisted of small samples and gave confusing results. This systematic review and meta-analysis aims to estimate the effects of HCT for adults with MS. We searched the database of CNKI, PUBMED, EMBASE, WEB of SCIENCE and the Cochrane Center Register of Controlled Trials to find initial studies and selected the appropriate researches included in the meta-analysis based on the inclusion and exclusion criteria. I2 was used to evaluate the heterogeneity and meta-regression was used for finding the source. Random effort model was performed to pool the data and funnel plot was drawn to determine publication bias. Six or eight single-arm clinical trials studies were included. The I2 value was 0.77 and 0.93, suggesting a heavy heterogeneity between studies. However, meta-regression analysis did not find the source of heterogeneity in which the publication country and follow up time were the influencing factors. Compared with baseline, the EDSS score of MS patients after HCT has a statistical decrease of 0.62 (95% CI 0.14, 1.10) at the 12th month and 1.26 (95%CI: 0.38, 2.14) at the follow up time ending point respectively. Available evidence suggests some clinical benefits of HCT combined with immunotherapy on MS. Due to wide confidence intervals that are characteristics of small evidence bases, further investigations to provide enough baseline information according to the RCTs are needed for further analysis, such as subgroup analysis and meta-regression analysis. PMID:27188734

  7. 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

  8. Epithelial stem cells.

    PubMed

    Draheim, Kyle M; Lyle, Stephen

    2011-01-01

    It is likely that adult epithelial stem cells will be useful in the treatment of diseases, such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa, and alopecias. Additionally, other skin problems such as burn wounds, chronic wounds, and ulcers will benefit from stem cell-related therapies. However, there are many questions that need to be answered before this goal can be realized. The most important of these questions is what regulates the adhesion of stem cells to the niche versus migration to the site of injury. We have started to identify the mechanisms involved in this decision-making process. PMID:21618097

  9. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  10. Cancer stem cells and exosome signaling.

    PubMed

    Hannafon, Bethany N; Ding, Wei-Qun

    2015-01-01

    Exosomes have been recognized as mediators of intercellular communication among different cell populations in various biological model systems. By transfer of signaling molecules such as proteins, lipids, and RNAs between different cell types, exosomes are implicated in both physiological and pathological processes. The tumor microenvironment consists of multiple types of cells including adult stem cells, cancer stem cells, and stromal cells. These cells are known to intercommunicate with each other thereby modulating tumor progression. Recent studies have provided evidence demonstrating that exosomes mediate the interactions among different types of cells within the tumor microenvironment, providing new insight into how these cells interact with each other through exosome signaling. This review is focused on recent studies that have examined exosome-mediated intercommunication among cancer stem cells, adult stem cells, cancer cells, and stromal cells within the tumor microenvironment. Based on the current literature, it seems clear that adult stem cells and cancer stem cells secret exosomes that can be transferred to their surrounding cells thereby modulating cancer progression. Likewise, cancer cells and stromal cells also release exosomes that can be taken up by cancer stem cells or adult stem cells, leading to alterations to their phenotype. The molecular mechanisms and biological consequences of the exosome-mediated interactions of these cells remain to be further elucidated. A better understanding of how exosomes mediate intercellular communication in the tumor microenvironment and the specific biological consequences of these interactions will likely offer new opportunities in the development of diagnostic or therapeutic strategies against cancer. PMID:27358879

  11. Cancer stem cells and exosome signaling

    PubMed Central

    Hannafon, Bethany N.

    2015-01-01

    Exosomes have been recognized as mediators of intercellular communication among different cell populations in various biological model systems. By transfer of signaling molecules such as proteins, lipids, and RNAs between different cell types, exosomes are implicated in both physiological and pathological processes. The tumor microenvironment consists of multiple types of cells including adult stem cells, cancer stem cells, and stromal cells. These cells are known to intercommunicate with each other thereby modulating tumor progression. Recent studies have provided evidence demonstrating that exosomes mediate the interactions among different types of cells within the tumor microenvironment, providing new insight into how these cells interact with each other through exosome signaling. This review is focused on recent studies that have examined exosome-mediated intercommunication among cancer stem cells, adult stem cells, cancer cells, and stromal cells within the tumor microenvironment. Based on the current literature, it seems clear that adult stem cells and cancer stem cells secret exosomes that can be transferred to their surrounding cells thereby modulating cancer progression. Likewise, cancer cells and stromal cells also release exosomes that can be taken up by cancer stem cells or adult stem cells, leading to alterations to their phenotype. The molecular mechanisms and biological consequences of the exosome-mediated interactions of these cells remain to be further elucidated. A better understanding of how exosomes mediate intercellular communication in the tumor microenvironment and the specific biological consequences of these interactions will likely offer new opportunities in the development of diagnostic or therapeutic strategies against cancer.

  12. Plant Stem Cells.

    PubMed

    Greb, Thomas; Lohmann, Jan U

    2016-09-12

    Among the trending topics in the life sciences, stem cells have received a fair share of attention in the public debate - mostly in connection with their potential for biomedical application and therapies. While the promise of organ regeneration and the end of cancer have captured our imagination, it has gone almost unnoticed that plant stem cells represent the ultimate origin of much of the food we eat, the oxygen we breathe, as well the fuels we burn. Thus, plant stem cells may be ranked among the most important cells for human well-being. Research by many labs in the last decades has uncovered a set of independent stem cell systems that fulfill the specialized needs of plant development and growth in four dimensions. Surprisingly, the cellular and molecular design of these systems is remarkably similar, even across diverse species. In some long-lived plants, such as trees, plant stem cells remain active over hundreds or even thousands of years, revealing the exquisite precision in the underlying control of proliferation, self-renewal and differentiation. In this minireview, we introduce the basic features of the three major plant stem cell systems building on these facts, highlight their modular design at the level of cellular layout and regulatory underpinnings and briefly compare them with their animal counterparts. PMID:27623267

  13. Pituitary stem cells: candidates and implications.

    PubMed

    Nassiri, Farshad; Cusimano, Michael; Zuccato, Jeff A; Mohammed, Safraz; Rotondo, Fabio; Horvath, Eva; Syro, Luis V; Kovacs, Kalman; Lloyd, Ricardo V

    2013-09-01

    The pituitary is the master endocrine gland of the body. It undergoes many changes after birth, and these changes may be mediated by the differentiation of pituitary stem cells. Stem cells in any tissue source must display (1) pluripotent capacity, (2) capacity for indefinite self-renewal, and (3) a lack of specialization. Unlike neural stem cells identified in the hippocampus and subventricular zone, pituitary stem cells are not associated with one specific cell type. There are many major candidates that are thought to be potential pituitary stem cell sources. This article reviews the evidence for each of the major cell types and discuss the implications of identifying a definitive pituitary stem cell type. PMID:23423660

  14. Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

    PubMed Central

    Mierzejewska, Katarzyna; Borkowska, Sylwia; Suszynska, Ewa; Suszynska, Malwina; Poniewierska-Baran, Agata; Maj, Magda; Pedziwiatr, Daniel; Adamiak, Mateusz; Abdel-Latif, Ahmed; Kakar, Sham S.; Ratajczak, Janina; Kucia, Magda

    2015-01-01

    Evidence has accumulated that hematopoietic stem progenitor cells (HSPCs) share several markers with the germline, a connection supported by reports that prolactin, androgens, and estrogens stimulate hematopoiesis. To address this issue more directly, we tested the expression of receptors for pituitary-derived hormones, such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), on purified murine bone marrow (BM) cells enriched for HSPCs and tested the functionality of these receptors in ex vivo signal transduction studies and in vitro clonogenic assays. We also tested whether administration of pituitary- and gonad-derived sex hormones (SexHs) increases incorporation of bromodeoxyuridine (BrdU) into HSPCs and expansion of hematopoietic clonogenic progenitors in mice and promotes recovery of blood counts in sublethally irradiated animals. We report for the first time that HSPCs express functional FSH and LH receptors and that both proliferate in vivo and in vitro in response to stimulation by pituitary SexHs. Furthermore, based on our observations that at least some of CD45− very small embryonic-like stem cells (VSELs) may become specified into CD45+ HSPCs, we also evaluated the expression of pituitary and gonadal SexHs receptors on these cells and tested whether these quiescent cells may expand in vivo in response to SexHs administration. We found that VSELs express SexHs receptors and respond in vivo to SexHs stimulation, as evidenced by BrdU accumulation. Since at least some VSELs share several markers characteristic of migrating primordial germ cells and can be specified into HSPCs, this observation sheds new light on the BM stem cell hierarchy. PMID:25607657

  15. Epigenetic regulation in adult stem cells and cancers

    PubMed Central

    2013-01-01

    Adult stem cells maintain tissue homeostasis by their ability to both self-renew and differentiate to distinct cell types. Multiple signaling pathways have been shown to play essential roles as extrinsic cues in maintaining adult stem cell identity and activity. Recent studies also show dynamic regulation by epigenetic mechanisms as intrinsic factors in multiple adult stem cell lineages. Emerging evidence demonstrates intimate crosstalk between these two mechanisms. Misregulation of adult stem cell activity could lead to tumorigenesis, and it has been proposed that cancer stem cells may be responsible for tumor growth and metastasis. However, it is unclear whether cancer stem cells share commonalities with normal adult stem cells. In this review, we will focus on recent discoveries of epigenetic regulation in multiple adult stem cell lineages. We will also discuss how epigenetic mechanisms regulate cancer stem cell activity and probe the common and different features between cancer stem cells and normal adult stem cells. PMID:24172544

  16. Evidence for ovarian granulosa stem cells: telomerase activity and localization of the telomerase ribonucleic acid component in bovine ovarian follicles.

    PubMed

    Lavranos, T C; Mathis, J M; Latham, S E; Kalionis, B; Shay, J W; Rodgers, R J

    1999-08-01

    We have previously postulated that granulosa cells of developing follicles arise from a population of stem cells. Stem cells and cancer cells can divide indefinitely partly because they express telomerase. Telomerase is a ribonucleoprotein enzyme that repairs the ends of telomeres that otherwise shorten progressively upon each successive cell division. In this study we carried out cell cycle analyses and examined telomerase expression to examine our hypothesis. Preantral (60-100 microm) and small (1 mm) follicles, as well as granulosa cells from medium-sized (3 mm) and large (6-8 mm) follicles, were isolated. Cell cycle analyses and expression of Ki-67, a cell cycle-related protein, were undertaken on follicles of each size (n = 3) by flow cytometry; 12% to 16% of granulosa cells in all follicles were in the S phase, and less than 2% were in the G(2)/M phase. Telomerase activity (n = 3) was highest in the small preantral follicles, declining at the 1-mm stage and even further at the 3-mm stage. In situ hybridization histochemistry was carried out on bovine ovaries, and telomerase RNA was detected in the granulosa cells of growing follicles but not primordial follicles. Two major patterns of staining were observed in the membrana granulosa of antral follicles: staining in the middle and antral layers, and staining in the middle and basal layers. No staining was detected in oocytes. Our results strongly support our hypothesis that granulosa cells arise from a population of stem cells. PMID:10411512

  17. Aneuploidy in stem cells

    PubMed Central

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to reality. However, as somatic cells might have accumulated various chromosomal abnormalities, including aneuploidies throughout their lives, the resulting IPSCs might no longer carry the perfect blueprint for the tissue to be generated, or worse, become at risk of adopting a malignant fate. In this review, we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore, we review the differences between how somatic cells and stem cells respond to aneuploidy. PMID:27354891

  18. Host induction by transplanted neural stem cells in the spinal cord: further evidence for an adult spinal cord neurogenic niche

    PubMed Central

    Xu, Leyan; Mahairaki, Vasiliki; Koliatsos, Vassilis E

    2013-01-01

    Aim To explore the hypothesis that grafts of exogenous stem cells in the spinal cord of athymic rats or rats with transgenic motor neuron disease can induce endogenous stem cells and initiate intrinsic repair mechanisms that can be exploited in amyotrophic lateral sclerosis therapeutics. Materials & methods Human neural stem cells (NSCs) were transplanted into the lower lumbar spinal cord of healthy rats or rats with transgenic motor neuron disease to explore whether signals related to stem cells can initiate intrinsic repair mechanisms in normal and amyotrophic lateral sclerosis subjects. Patterns of migration and differentiation of NSCs in the gray and white matter, with emphasis on the central canal region and ependymal cell-driven neurogenesis, were analyzed. Results Findings suggest that there is extensive cross-signaling between transplanted NSCs and a putative neurogenic niche in the ependyma of the lower lumbar cord. The formation of a neuronal cord from NSC-derived cells next to ependyma suggests that this structure may serve a mediating or auxiliary role for ependymal induction. Conclusion These findings raise the possibility that NSCs may stimulate endogenous neurogenesis and initiate intrinsic repair mechanisms in the lower spinal cord. PMID:23164079

  19. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  20. Cancer stem cell signaling pathways.

    PubMed

    Matsui, William H

    2016-09-01

    Tissue development and homeostasis are governed by the actions of stem cells. Multipotent cells are capable of self-renewal during the course of one's lifetime. The accurate and appropriate regulation of stem cell functions is absolutely critical for normal biological activity. Several key developmental or signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the Janus-activated kinase/signal transducer and activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3-kinase/phosphatase and tensin homolog, and nuclear factor-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Unsurprisingly, many of these crucial signaling pathways are dysregulated in cancer. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells capable of self-renewal, differentiation, and generation of serially transplantable heterogeneous tumors of several types of cancer. PMID:27611937

  1. Stem cell strategies for Alzheimer's disease therapy.

    PubMed

    Sugaya, K; Alvarez, A; Marutle, A; Kwak, Y D; Choumkina, E

    2006-06-01

    We have found much evidence that the brain is capable of regenerating neurons after maturation. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicating that HNSCs may be a promising candidate for cell-replacement therapies for neurodegenerative diseases including Alzheimer's disease (AD). However, ethical and practical issues associated with HNSCs compel us to explore alternative strategies. Here, we report novel technologies to differentiate adult human mesenchymal stem cells, a subset of stromal cells in the bone marrow, into neural cells by modifying DNA methylation or over expression of nanog, a homeobox gene expressed in embryonic stem cells. We also report peripheral administrations of a pyrimidine derivative that increases endogenous stem cell proliferation improves cognitive function of the aged animal. Although these results may promise a bright future for clinical applications used towards stem cell strategies in AD therapy, we must acknowledge the complexity of AD. We found that glial differentiation takes place in stem cells transplanted into amyloid-( precursor protein (APP) transgenic mice. We also found that over expression of APP gene or recombinant APP treatment causes glial differentiation of stem cells. Although further detailed mechanistic studies may be required, RNA interference of APP or reduction of APP levels in the brain can significantly reduced glial differentiation of stem cells and may be useful in promoting neurogenesis after stem cell transplantation. PMID:16953146

  2. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research. PMID:21044008

  3. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  4. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2002-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  5. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy. PMID:18729799

  6. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  7. [The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: I. The evidences for the use of immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation].

    PubMed

    Callegaro, Dagoberto; Lana-Peixoto, Marco Aurélio; Moreira, Marcos Aurélio; Marchiori, Paulo Eurípedes; Bacheschi, Luiz Alberto; Arruda, Walter Oleschko; Campos, Gilberto Belisário; Lino, Angelina Maria Martins; Melo, Aílton Souza; Rocha, Fernando Coronetti Gomes; Ferreira, Maria Lúcia Brito; Ataide, Luiz; Maciel, Damacio Ramón Kaimen

    2002-09-01

    Since the sixties immunosuppressive agents have been used in the treatment of multiple sclerosis as there was cumulating evidence of the inflammatory nature of the disease. Cyclophosphamide, azathioprine and methotrexate have been the most frequently employed drugs whereas other agents such as cyclosporine and cladribine have been recently tested for RRMS. Mithoxantrone, on the other hand, was approved by the FDA for treatment of aggressive forms of the disease. Other immunointerventions such as plasma exchange and autologous hematopoietic stem cell transplantation have recently been employed in some special circumstances. This paper analyses the most important published data on the use of the immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation according to the classes of evidences and types of recommendations of these drugs and immunointerventions. It provides sufficient information to support the guidelines expressed in the BCTRIMS Expanded Consensus on Treatment of MS. PMID:12364965

  8. 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.

  9. Plasticity of hematopoietic stem cells.

    PubMed

    Ogawa, Makio; LaRue, Amanda C; Mehrotra, Meenal

    2015-01-01

    Almost two decades ago, a number of cell culture and preclinical transplantation studies suggested the striking concept of the tissue-reconstituting ability of hematopoietic stem cells (HSCs). While this heralded an exciting time of radically new therapies for disorders of many organs and tissues, the concept was soon mired by controversy and remained dormant. This chapter provides a brief review of evidence for HSC plasticity including our findings based on single HSC transplantation in mouse. These studies strongly support the concept that HSCs are pluripotent and may be the source for the majority, if not all, of the cell types in our body. PMID:26590762

  10. Head and Neck Cancer Stem Cells

    PubMed Central

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the “drivers” of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  11. Head and neck cancer stem cells.

    PubMed

    Krishnamurthy, S; Nör, J E

    2012-04-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  12. Stem cell treatment of degenerative eye disease☆

    PubMed Central

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

    2015-01-01

    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. PMID:25752437

  13. Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Insulin-Producing Cells: Evidence for Further Maturation In Vivo

    PubMed Central

    Gabr, Mahmoud M.; Zakaria, Mahmoud M.; Refaie, Ayman F.; Khater, Sherry M.; Ashamallah, Sylvia A.; Ismail, Amani M.; El-Halawani, Sawsan M.; Ghoneim, Mohamed A.

    2015-01-01

    The aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were differentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks after transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro differentiation, all pancreatic endocrine genes were expressed, albeit at very low values. The percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic 8 ± 3 days after transplantation. Thereafter, the percentage of IPCs reached a mean of ~18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. The ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation. PMID:26064925

  14. Salivary Gland Cancer Stem Cells

    PubMed Central

    Adams, April; Warner, Kristy; Nör, Jacques E.

    2013-01-01

    Emerging evidence suggests the existence of a tumorigenic population of cancer cells that demonstrate stem cell-like properties such as self-renewal and multipotency. These cells, termed cancer stem cells (CSC), are able to both initiate and maintain tumor formation and progression. Studies have shown that CSC are resistant to traditional chemotherapy treatments preventing complete eradication of the tumor cell population. Following treatment, CSC are able to re-initiate tumor growth leading to patient relapse. Salivary gland cancers are relatively rare but constitute a highly significant public health issue due to the lack of effective treatments. In particular, patients with mucoepidermoid carcinoma or adenoid cystic carcinoma, the two most common salivary malignancies, have low long-term survival rates due to the lack of response to current therapies. Considering the role of CSC in resistance to therapy in other tumor types, it is possible that this unique sub-population of cells is involved in resistance of salivary gland tumors to treatment. Characterization of CSC can lead to better understanding of the pathobiology of salivary gland malignancies as well as to the development of more effective therapies. Here, we make a brief overview of the state-of-the-science in salivary gland cancer, and discuss possible implications of the cancer stem cell hypothesis to the treatment of salivary gland malignancies. PMID:23810400

  15. Cancer stem cells in multiple myeloma.

    PubMed

    Ghosh, Nilanjan; Matsui, William

    2009-05-01

    Several key observations providing evidence for the cancer stem cell hypothesis and insights into the unique biology of these cells have come from the study of multiple myeloma. These include evidence that cancer cells may be functionally heterogeneous in spite of their genetic homogeneity and that malignant progenitors share many biological features with normal adult stem cells including drug resistance and regulatory processes governing self-renewal. We review studies that have examined clonogenic cells in multiple myeloma, highlight controversies regarding the cell of origin in multiple myeloma, and discuss potential targeting strategies. PMID:18809245

  16. Stem cell sources to treat diabetes.

    PubMed

    Furth, Mark E; Atala, Anthony

    2009-03-01

    We review progress towards the goal of utilizing stem cells as a source of engineered pancreatic beta-cells for therapy of diabetes. Protocols for the in vitro differentiation of embryonic stem (ES) cells based on normal developmental cues have generated beta-like cells that produce high levels of insulin, albeit at low efficiency and without full responsiveness to extracellular levels of glucose. Induced pluripotent stem (iPS) cells also can yield insulin-producing cells following similar approaches. An important recent report shows that when transplanted into mice, human ES-derived cells with a phenotype corresponding to pancreatic endoderm matured to yield cells capable of maintaining near-normal regulation of blood sugar [Kroon et al., 2008]. Major hurdles that must be overcome to enable the broad clinical translation of these advances include teratoma formation by ES and iPS cells, and the need for immunosuppressive drugs. Classes of stem cells that can be expanded extensively in culture but do not form teratomas, such as amniotic fluid-derived stem cells and hepatic stem cells, offer possible alternatives for the production of beta-like cells, but further evidence is required to document this potential. Generation of autologous iPS cells should prevent transplant rejection, but may prove prohibitively expensive. Banking strategies to identify small numbers of stem cell lines homozygous for major histocompatibility loci have been proposed to enable beneficial genetic matching that would decrease the need for immunosuppression. PMID:19130494

  17. Functional Multipotency of Stem Cells: A Conceptual Review of Neurotrophic Factor-Based Evidence and Its Role in Translational Research

    PubMed Central

    Teng, Yang D; Yu, Dou; Ropper, Alexander E; Li, Jianxue; Kabatas, Serdar; Wakeman, Dustin R; Wang, Junmei; Sullivan, Maryrose P; Redmond, D. Eugene; Langer, Robert; Snyder, Evan Y; Sidman, Richard L

    2011-01-01

    We here propose an updated concept of stem cells (SCs), with an emphasis on neural stem cells (NSCs). The conventional view, which has touched principally on the essential property of lineage multipotency (e.g., the ability of NSCs to differentiate into all neural cells), should be broadened to include the emerging recognition of biofunctional multipotency of SCs to mediate systemic homeostasis, evidenced in NSCs in particular by the secretion of neurotrophic factors. Under this new conceptual context and taking the NSC as a leading example, one may begin to appreciate and seek the “logic” behind the wide range of molecular tactics the NSC appears to serve at successive developmental stages as it integrates into and prepares, modifies, and guides the surrounding CNS micro- and macro-environment towards the formation and self-maintenance of a functioning adult nervous system. We suggest that embracing this view of the “multipotency” of the SCs is pivotal for correctly, efficiently, and optimally exploiting stem cell biology for therapeutic applications, including reconstitution of a dysfunctional CNS. PMID:22654717

  18. The biology of hematopoietic stem cells.

    PubMed

    Szilvassy, Stephen J

    2003-01-01

    Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems. PMID:14734085

  19. 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

  20. [Mesenchymal stem cells. A review.].

    PubMed

    Sigurjónsson, O E; Guðmundsson, K O; Guðmundsson, S

    2001-01-01

    The bone marrow contains various types of stem cells. Among them are hematopoietic stem cells, which are the precursors of all blood cells, and mesenchymal stem cells. Mesenchymal stem cells have recently received a lot of attention in biological research because of their capability to self renewal, to expand and transdifferentiate into many different cell types; bone cells, adipocytes, chondrocytes, tendocytes, neural cells and stromal cells of the bone marrow. Mesenchymal stem cells can be cultured in vitro although their differentiation potential is not yet fully understood. Several experiments have been conducted in animal models where mesenchymal stem cells have been transplanted in order to enhance hematopoiesis or to facilitate the repair of mesenchymal tissue. Similar experiments are being conducted in humans. Mesenchymal stem cells are believed to be able to enhance hematopoietic stem cells transplantation by rebuilding the bone marrow microenvironment which is damaged after radiation- and/or chemotherapy. Mesenchymal stem cells are promising as vehicles for gene transfer and therapy. It may prove possible to tranduce them with a gene coding for a defective protein i.e. collagen I in osteogenesis imperfecta. The cells could then be expanded ex vivo and transplanted to the patients where they home to the bone marrow, differentiate and produce the intact protein. Future medicine will probably involve mesenchymal stem cells in various treatment settings. PMID:17018999

  1. Dental mesenchymal stem cells.

    PubMed

    Sharpe, Paul T

    2016-07-01

    Mammalian teeth harbour mesenchymal stem cells (MSCs), which contribute to tooth growth and repair. These dental MSCs possess many in vitro features of bone marrow-derived MSCs, including clonogenicity, expression of certain markers, and following stimulation, differentiation into cells that have the characteristics of osteoblasts, chondrocytes and adipocytes. Teeth and their support tissues provide not only an easily accessible source of MSCs but also a tractable model system to study their function and properties in vivo In addition, the accessibility of teeth together with their clinical relevance provides a valuable opportunity to test stem cell-based treatments for dental disorders. This Review outlines some recent discoveries in dental MSC function and behaviour and discusses how these and other advances are paving the way for the development of new biologically based dental therapies. PMID:27381225

  2. Stem cells versus plasticity in liver and pancreas regeneration.

    PubMed

    Kopp, Janel L; Grompe, Markus; Sander, Maike

    2016-03-01

    Cell replacement in adult organs can be achieved through stem cell differentiation or the replication or transdifferentiation of existing cells. In the adult liver and pancreas, stem cells have been proposed to replace tissue cells, particularly following injury. Here we review how specialized cell types are produced in the adult liver and pancreas. Based on current evidence, we propose that the plasticity of differentiated cells, rather than stem cells, accounts for tissue repair in both organs. PMID:26911907

  3. Stem cell aging

    PubMed Central

    Muller-Sieburg, Christa; Sieburg, Hans B.

    2009-01-01

    The question whether stem cells age remains an enigma. Traditionally, aging was thought to change the properties of hematopoietic stem cells (HSC). We discuss here a new model of stem cell aging that challenges this view. It is now well-established that the HSC compartment is heterogeneous, consisting of epigenetically fixed subpopulations of HSC that differ in self-renewal and differentiation capacity. New data show that the representation of these HSC subsets changes during aging. HSC that generate lymphocyte-rich progeny are depleted, while myeloid-biased HSC are enriched in the aged HSC compartment. Myeloid-biased HSC, even when isolated from young donors, have most of the characteristics that had been attributed to aged HSC. Thus, the distinct behavior of the HSC isolated from aged hosts is due to the accumulation of myeloid-biased HSC. By extension this means that the properties of individual HSC are not substantially changed during the lifespan of the organism and that aged hosts do not contain many aged HSC. Myeloid-biased HSC give rise to mature cells slowly but contribute for a long time to peripheral hematopoiesis. We propose that such slow, “lazy” HSC are less likely to be transformed and therefore may safely sustain hematopoiesis for a long time. PMID:19066464

  4. Epigenetic targeting of ovarian cancer stem cells.

    PubMed

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  5. The biology of cancer stem cells.

    PubMed

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. PMID:17645413

  6. Stem Cells in Aging

    PubMed Central

    Yunis, Edmond J.; Zúñiga, Joaquin; Koka, Prasad S.; Husain, Zaheed; Romero, Viviana; Stern, Joel N.H.; Fridkis-Hareli, Masha

    2008-01-01

    Aging is a genetically programmed decline in the functional effectiveness of the organism. It is manifested by a collective group of changes in cells or organs that occur over the course of a lifespan, limiting the duration of life. Longevity usually refers to long-lived members of a population within species. Organs develop and can involute according to specific timetables. Such timetables correlate with a preordained proliferative capacity of cells mediated by cell and organ clocks. In this review, we discuss different aspects related to genetic and environmental factors that are involved in determining life span. We discuss the influence of ontogenic, genetic and environmental factors in aging. The genetic factors can be studied in embryonic stem cells (ESC) and in niches (microenvironments) of stem cells (SC) using cellular or experimental animal models. We discuss molecular mechanisms involving genes and proteins associated with death pathways, niches, or hubs, on longevity. Moreover, we also discuss genes and proteins, associated with death pathways, on longevity. Unraveling these mechanisms may further our understanding of human aging leading to development of therapeutic interventions with the potential of prolonging life. PMID:19030125

  7. 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. PMID:12714568

  8. Making a Hematopoietic Stem Cell

    PubMed Central

    Daniel, Michael G.; Pereira, Carlos-Filipe; Lemischka, Ihor R.; Moore, Kateri A.

    2016-01-01

    Previous attempts to either generate or expand hematopoietic stem cells (HSCs) in vitro have involved either ex vivo expansion of pre-existing patient or donor HSCs or de novo generation from pluripotent stem cells (PSCs), comprising both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs alleviated ESC ethical issues but attempts to generate functional mature hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful. New efforts focus on directly reprogramming somatic cells into definitive HSCs and HSPCs. To meet clinical needs and to advance drug discovery and stem cell therapy, alternative approaches are necessary. In this review, we synthesize the strategies used and the key findings made in recent years by those trying to make an HSC. PMID:26526106

  9. Multiple Myeloma Cancer Stem Cells

    PubMed Central

    Huff, Carol Ann; Matsui, William

    2008-01-01

    Multiple myeloma is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic bone disease. The disease is highly responsive to a wide variety of anticancer treatments including conventional cytotoxic chemotherapy, corticosteroids, radiation therapy, and a growing number of agents with novel mechanisms of action. However, few if any patients are cured with these modalities and relapse remains a critical issue. A better understanding of clonogenic multiple myleoma cells is essential to ultimately improving long-term outcomes, but the nature of the cells responsible for myeloma regrowth and disease relapse is unclear. We review evidence that functional heterogeneity exists in multiple myeloma and discuss potential strategies and clinical implications of the stem-cell model of cancer in this disease. PMID:18539970

  10. Mimicking Stem Cell Niches to Increase Stem Cell Expansion

    PubMed Central

    Dellatore, Shara M.; Garcia, A. Sofia; Miller, William M.

    2008-01-01

    Summary Niches regulate lineage-specific stem cell self-renewal vs. differentiation in vivo and are comprised of supportive cells and extracellular matrix components arranged in a 3-dimensional topography of controlled stiffness in the presence of oxygen and growth factor gradients. Mimicking stem cell niches in a defined manner will facilitate production of the large numbers of stem cells needed to realize the promise of regenerative medicine and gene therapy. Progress has been made in mimicking components of the niche. Immobilizing cell-associated Notch ligands increased the self-renewal of hematopoietic (blood) stem cells. Culture on a fibrous scaffold that mimics basement membrane texture increased the expansion of hematopoietic and embryonic stem cells. Finally, researchers have created intricate patterns of cell-binding domains and complex oxygen gradients. PMID:18725291

  11. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  12. How Necessary is the Vasculature in the Life of Neural Stem and Progenitor Cells? Evidence from Evolution, Development and the Adult Nervous System

    PubMed Central

    Koutsakis, Christos; Kazanis, Ilias

    2016-01-01

    Augmenting evidence suggests that such is the functional dependance of neural stem cells (NSCs) on the vasculature that they normally reside in “perivascular niches”. Two examples are the “neurovascular” and the “oligovascular” niches of the adult brain, which comprise specialized microenvironments where NSCs or oligodendrocyte progenitor cells survive and remain mitotically active in close proximity to blood vessels (BVs). The often observed co-ordination of angiogenesis and neurogenesis led to these processes being described as “coupled”. Here, we adopt an evo-devo approach to argue that some stages in the life of a NSC, such as specification and commitment, are independent of the vasculature, while stages such as proliferation and migration are largely dependent on BVs. We also explore available evidence on the possible involvement of the vasculature in other phenomena such as the diversification of NSCs during evolution and we provide original data on the senescence of NSCs in the subependymal zone stem cell niche. Finally, we will comment on the other side of the story; that is, on how much the vasculature is dependent on NSCs and their progeny. PMID:26909025

  13. Skeletal stem cells.

    PubMed

    Bianco, Paolo; Robey, Pamela G

    2015-03-15

    Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes in defined in vivo assays. These lineages emerge in a specific sequence during embryonic development and post natal growth, and together comprise a continuous anatomical system, the bone-bone marrow organ. SSCs conjoin skeletal and hematopoietic physiology, and are a tool for understanding and ameliorating skeletal and hematopoietic disorders. Here and in the accompanying poster, we concisely discuss the biology of SSCs in the context of the development and postnatal physiology of skeletal lineages, to which their use in medicine must remain anchored. PMID:25758217

  14. The chiaroscuro stem cell: a unified stem cell theory.

    PubMed

    Quesenberry, Peter J; Colvin, Gerald A; Lambert, Jean-Francois

    2002-12-15

    Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraftable stem cell may be partially masked in nonsynchronized marrow cell populations. A general model indicates a marrow cell that can continually change its surface receptor expression and thus responds to external stimuli differently at different points in the cell cycle. PMID:12393432

  15. Mechanotransduction: Tuning Stem Cells Fate

    PubMed Central

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

    2011-01-01

    It is a general concern that the success of regenerative medicine-based applications is based on the ability to recapitulate the molecular events that allow stem cells to repair the damaged tissue/organ. To this end biomaterials are designed to display properties that, in a precise and physiological-like fashion, could drive stem cell fate both in vitro and in vivo. The rationale is that stem cells are highly sensitive to forces and that they may convert mechanical stimuli into a chemical response. In this review, we describe novelties on stem cells and biomaterials interactions with more focus on the implication of the mechanical stimulation named mechanotransduction. PMID:24956164

  16. Stem Cells, Redox Signaling, and Stem Cell Aging

    PubMed Central

    Liang, Raymond

    2014-01-01

    Abstract Significance: Functional stem cell decline has been postulated to result in loss of maintenance of tissue homeostasis leading to organismal decline and diseases of aging. Recent Advances: Recent findings implicate redox metabolism in the control of stem cell pool and stem cell aging. Although reactive oxygen species (ROS) are better known for their damaging properties to DNA, proteins and lipids, recent findings suggest that ROS may also be an integral physiological mediator of cellular signaling in primary cells. Critical Issues: Here we review recent published work on major signaling pathways and transcription factors that are regulated by ROS and mediate ROS regulation of stem cell fate. We will specifically focus on how alterations in this regulation may be implicated in disease and particularly in diseases of stem cell aging. In general, based on the work described here we propose a model in which ROS function as stem cell rheostat. Future Directions: Future work in elucidating how ROS control stem cell cycling, apoptotic machinery, and lineage determination should shed light on mechanisms whereby ROS may control stem cell aging. Antioxid. Redox Signal. 20, 1902–1916. PMID:24383555

  17. Stem cells: insights into the secretome.

    PubMed

    Makridakis, Manousos; Roubelakis, Maria G; Vlahou, Antonia

    2013-11-01

    Stem cells have been considered as possible therapeutic vehicles for different health related problems such as cardiovascular and neurodegenerative diseases and cancer. Secreted molecules are key mediators in cell-cell interactions and influence the cross talk with the surrounding tissues. There is strong evidence supporting that crucial cellular functions such as proliferation, differentiation, communication and migration are strictly regulated from the cell secretome. The investigation of stem cell secretome is accumulating continuously increasing interest given the potential use of these cells in regenerative medicine. The scope of the review is to report the main findings from the investigation of stem cell secretome by the use of contemporary proteomics methods and discuss the current status of research in the field. This article is part of a Special Issue entitled: An Updated Secretome. PMID:23376432

  18. Intestinal stem cells and epithelial-mesenchymal interactions in the crypt and stem cell niche

    PubMed Central

    Shaker, Anisa; Rubin, Deborah C.

    2010-01-01

    The intestinal epithelium contains a rapidly proliferating and perpetually differentiating epithelium. The principal functional unit of the small intestine is the crypt-villus axis. Stem cells located in the crypts of Lieberkühn give rise to proliferating progenitor or transit amplifying cells that differentiate into the four major epithelial cell types. The study of adult gastrointestinal tract stem cells has progressed rapidly with the recent discovery of a number of putative stem cell markers. Substantial evidence suggests that there are two populations of stem cells: long-term quiescent (reserved) and actively cycling (primed) stem cells. These are in adjoining locations and are presumably maintained by the secretion of specific proteins generated in a unique microenvironment or stem cell niche surrounding each population. The relationship between these two populations, and the cellular sources and composition of the surrounding environment remains to be defined, and is an active area of research. In this review we will outline progress in identifying stem cells and defining epithelial-mesenchymal interactions in the crypt. We will summarize early advances using stem cells for therapy of gastrointestinal disorders. PMID:20801415

  19. [Stem cells and cardiac regeneration].

    PubMed

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research. PMID:17240634

  20. Adult stem cells underlying lung regeneration

    PubMed Central

    2012-01-01

    Despite the massive toll in human suffering imparted by degenerative lung disease, including COPD, idiopathic pulmonary fibrosis and ARDS, the scientific community has been surprisingly agnostic regarding the potential of lung tissue and, in particular, the alveoli, to regenerate. However, there is circumstantial evidence in humans and direct evidence in mice that ARDS triggers robust regeneration of lung tissue rather than irreversible fibrosis. The stem cells responsible for this remarkable regenerative process has garnered tremendous attention, most recently yielding a defined set of cloned human airway stem cells marked by p63 expression but with distinct commitment to differentiated cell types typical of the upper or lower airways, the latter of which include alveoli-like structures in vitro and in vivo. These recent advances in lung regeneration and distal airway stem cells and the potential of associated soluble factors in regeneration must be harnessed for therapeutic options in chronic lung disease. PMID:22333577

  1. Stem Cells, Progenitor Cells, and Lineage Decisions in the Ovary

    PubMed Central

    Hummitzsch, Katja; Anderson, Richard A.; Wilhelm, Dagmar; Wu, Ji; Telfer, Evelyn E.; Russell, Darryl L.; Robertson, Sarah A.

    2015-01-01

    Exploring stem cells in the mammalian ovary has unleashed a Pandora's box of new insights and questions. Recent evidence supports the existence of stem cells of a number of the different cell types within the ovary. The evidence for a stem cell model producing mural granulosa cells and cumulus cells is strong, despite a limited number of reports. The recent identification of a precursor granulosa cell, the gonadal ridge epithelial-like cell, is exciting and novel. The identification of female germline (oogonial) stem cells is still very new and is currently limited to just a few species. Their origins and physiological roles, if any, are unknown, and their potential to produce oocytes and contribute to follicle formation in vivo lacks robust evidence. The precursor of thecal cells remains elusive, and more compelling data are needed. Similarly, claims of very small embryonic-like cells are also preliminary. Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed. Another important issue is the role of the stroma in guiding the formation of the ovary, ovigerous cords, follicles, and surface epithelium. Immune cells may also play key roles in developmental patterning, given their critical roles in corpora lutea formation and regression. Thus, while the cellular biology of the ovary is extremely important for its major endocrine and fertility roles, there is much still to be discovered. This review draws together the current evidence and perspectives on this topic. PMID:25541635

  2. Involvement of Plant Stem Cells or Stem Cell-Like Cells in Dedifferentiation

    PubMed Central

    Jiang, Fangwei; Feng, Zhenhua; Liu, Hailiang; Zhu, Jian

    2015-01-01

    Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells) are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation. PMID:26635851

  3. The new stem cell biology.

    PubMed Central

    Quesenberry, Peter J.; Colvin, Gerald A.; Lambert, Jean-Francois; Frimberger, Angela E.; Dooner, Mark S.; Mcauliffe, Christina I.; Miller, Caroline; Becker, Pamela; Badiavas, Evangelis; Falanga, Vincent J.; Elfenbein, Gerald; Lum, Lawrence G.

    2002-01-01

    Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem cells express a wide variety of adhesion and cytokine receptors and respond quickly with migration and podia extensions on exposure to cytokines. These data suggest an "Open Chromatin" model of stem cell regulation in which there is a fluctuating continuum in the stem cell/progenitor cell compartments, rather than a hierarchical relationship. These observations, along with progress in using low dose treatments and tolerization approaches, suggest many new therapeutic strategies involving stem cells and the creation of a new medical specialty; stemology. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:12053709

  4. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

    The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

  5. Stem cells for spine surgery.

    PubMed

    Schroeder, Joshua; Kueper, Janina; Leon, Kaplan; Liebergall, Meir

    2015-01-26

    In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer's disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion. PMID:25621119

  6. 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

  7. The Adipose Mesenchymal Stem Cell Secretome Inhibits Inflammatory Responses of Microglia: Evidence for an Involvement of Sphingosine-1-Phosphate Signalling.

    PubMed

    Marfia, Giovanni; Navone, Stefania Elena; Hadi, Loubna Abdel; Paroni, Moira; Berno, Valeria; Beretta, Matteo; Gualtierotti, Roberta; Ingegnoli, Francesca; Levi, Vincenzo; Miozzo, Monica; Geginat, Jens; Fassina, Lorenzo; Rampini, Paolo; Tremolada, Carlo; Riboni, Laura; Campanella, Rolando

    2016-07-15

    Central nervous system (CNS) inflammation is primarily driven by microglial cells which secrete proinflammatory cytokines and undergo proliferation upon activation, as it occurs in neurodegenerative diseases. Uncontrolled or prolonged CNS inflammation is potentially harmful and can result in cellular damage. Recently, many studies have focused on human adipose tissue as an attractive source of cytokines with immunosuppressive properties that potentially modulate inflammation. Our study aimed to evaluate if different methods of human tissue collection could affect adipose mesenchymal stem cell (ADSC)-derived cytokine secretion and investigate the effects of ADSC secretome in modulating microglia activation and the possible implication of sphingosine-1-phosphate (S1P) in these effects. Our results demonstrate that the conditioned medium (CM) of ADSCs isolated by two different processing methods (lipoaspirate and Lipogems) significantly inhibited the lipopolysaccharide (LPS)-induced effects on microglia activation, including microglial expression of CD68, cytokine secretion, proliferation, and migration. Pulse studies with radiolabeled sphingosine demonstrated that LPS treatment of resting microglia induced a significant increase of both cellular and extracellular S1P. Moreover, and of relevance, FTY720, a functional antagonist of S1P receptor, inhibited the multiple LPS-induced proinflammatory effects on microglia, and S1P suppressed the anti-inflammatory effect of ADSC-CM. This suggests that LPS-mediated microglial activation is countered by ADSC-CM through the modulation of sphingosine kinase/S1P signalling. PMID:27217090

  8. Preclinical and Clinical Evidence of Mycobacterium tuberculosis Persistence in the Hypoxic Niche of Bone Marrow Mesenchymal Stem Cells after Therapy.

    PubMed

    Garhyan, Jaishree; Bhuyan, Seema; Pulu, Ista; Kalita, Deepjyoti; Das, Bikul; Bhatnagar, Rakesh

    2015-07-01

    Mycobacterium tuberculosis (MTB), the causative agent of pulmonary tuberculosis, is difficult to eliminate by antibiotic therapy. We recently identified CD271(+) bone marrow-mesenchymal stem cells (BM-MSCs) as a potential site of MTB persistence after therapy. Herein, we have characterized the potential hypoxic localization of the post-therapy MTB-infected CD271(+) BM-MSCs in both mice and human subjects. We first demonstrate that in a Cornell model of MTB persistence in mice, green fluorescent protein-labeled virulent MTB-strain H37Rv was localized to pimonidazole (an in vivo hypoxia marker) positive CD271(+) BM-MSCs after 90 days of isoniazid and pyrazinamide therapy that rendered animal's lung noninfectious. The recovered CD271(+) BM-MSCs from post-therapy mice, when injected into healthy mice, caused active tuberculosis infection in the animal's lung. Moreover, MTB infection significantly increased the hypoxic phenotype of CD271(+) BM-MSCs. Next, in human subjects, previously treated for pulmonary tuberculosis, the MTB-containing CD271(+) BM-MSCs exhibited high expression of hypoxia-inducible factor 1α and low expression of CD146, a hypoxia down-regulated cell surface marker of human BM-MSCs. These data collectively demonstrate the potential localization of MTB harboring CD271(+) BM-MSCs in the hypoxic niche, a critical microenvironmental factor that is well known to induce the MTB dormancy phenotype. PMID:26066709

  9. Stem cell mitochondria during aging.

    PubMed

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future. PMID:26851627

  10. FDA Warns About Stem Cell Claims

    MedlinePlus

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Claims Share Tweet Linkedin Pin it More sharing ... blood-forming system. back to top Regulation of Stem Cells FDA regulates stem cells in the U.S. to ...

  11. LncRNAs in Stem Cells

    PubMed Central

    Hu, Shanshan; Shan, Ge

    2016-01-01

    Noncoding RNAs are critical regulatory factors in essentially all forms of life. Stem cells occupy a special position in cell biology and Biomedicine, and emerging results show that multiple ncRNAs play essential roles in stem cells. We discuss some of the known ncRNAs in stem cells such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, adult stem cells, and cancer stem cells with a focus on long ncRNAs. Roles and functional mechanisms of these lncRNAs are summarized, and insights into current and future studies are presented. PMID:26880946

  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. Stem cell mechanics: Auxetic nuclei

    NASA Astrophysics Data System (ADS)

    Wang, Ning

    2014-06-01

    The nuclei of naive mouse embryonic stem cells that are transitioning towards differentiation expand when the cells are stretched and contract when they are compressed. What drives this auxetic phenotype is, however, unclear.

  14. Role of liver stem cells in hepatocarcinogenesis

    PubMed Central

    Xu, Lei-Bo; Liu, Chao

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

  15. Engineering of the Embryonic and Adult Stem Cell Niches

    PubMed Central

    Hosseinkhani, Mohsen; Shirazi, Reza; Rajaei, Farzad; Mahmoudi, Masoud; Mohammadi, Navid; Abbasi, Mahnaz

    2013-01-01

    Context Stem cells have the potential to generate a renewable source of cells for regenerative medicine due to their ability to self-renew and differentiate to various functional cell types of the adult organism. The extracellular microenvironment plays a pivotal role in controlling stem cell fate responses. Therefore, identification of appropriate environmental stimuli that supports cellular proliferation and lineage-specific differentiation is critical for the clinical application of the stem cell therapies. Evidence Acquisition Traditional methods for stem cells culture offer limited manipulation and control of the extracellular microenvironment. Micro engineering approaches are emerging as powerful tools to control stem cell-microenvironment interactions and for performing high-throughput stem cell experiments. Results In this review, we provided an overview of the application of technologies such as surface micropatterning, microfluidics, and engineered biomaterials for directing stem cell behavior and determining the molecular cues that regulate cell fate decisions. Conclusions Stem cells have enormous potential for therapeutic and pharmaceutical applications, because they can give rise to various cell types. Despite their therapeutic potential, many challenges, including the lack of control of the stem cell microenvironment remain. Thus, a greater understanding of stem cell biology that can be used to expand and differentiate embryonic and adult stem cells in a directed manner offers great potential for tissue repair and regenerative medicine. PMID:23682319

  16. Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Shen, Qin; Goderie, Susan K.; Jin, Li; Karanth, Nithin; Sun, Yu; Abramova, Natalia; Vincent, Peter; Pumiglia, Kevin; Temple, Sally

    2004-05-01

    Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.

  17. 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

  18. Chromatin, epigenetics and stem cells.

    PubMed

    Roloff, Tim C; Nuber, Ulrike A

    2005-03-01

    Epigenetics is a term that has changed its meaning with the increasing biological knowledge on developmental processes. However, its current application to stem cell biology is often imprecise and is conceptually problematic. This article addresses two different subjects, the definition of epigenetics and chromatin states of stem and differentiated cells. We describe mechanisms that regulate chromatin changes and provide an overview of chromatin states of stem and differentiated cells. Moreover, a modification of the current epigenetics definition is proposed that is not restricted by the heritability of gene expression throughout cell divisions and excludes translational gene expression control. PMID:15819395

  19. Stem cells for tooth engineering.

    PubMed

    Bluteau, G; Luder, H U; De Bari, C; Mitsiadis, T A

    2008-01-01

    Tooth development results from sequential and reciprocal interactions between the oral epithelium and the underlying neural crest-derived mesenchyme. The generation of dental structures and/or entire teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin and enamel. Although mesenchymal stem cells from different origins have been extensively studied in their capacity to form dentin in vitro, information is not yet available concerning the use of epithelial stem cells. The odontogenic potential resides in the oral epithelium and thus epithelial stem cells are necessary for both the initiation of tooth formation and enamel matrix production. This review focuses on the different sources of stem cells that have been used for making teeth in vitro and their relative efficiency. Embryonic, post-natal or even adult stem cells were assessed and proved to possess an enormous regenerative potential, but their application in dental practice is still problematic and limited due to various parameters that are not yet under control such as the high risk of rejection, cell behaviour, long tooth eruption period, appropriate crown morphology and suitable colour. Nevertheless, the development of biological approaches for dental reconstruction using stem cells is promising and remains one of the greatest challenges in the dental field for the years to come. PMID:18671204

  20. GPCRs in Stem Cell Function

    PubMed Central

    DOZE, VAN A.; PEREZ, DIANNE M.

    2013-01-01

    Many tissues of the body cannot only repair themselves, but also self-renew, a property mainly due to stem cells and the various mechanisms that regulate their behavior. Stem cell biology is a relatively new field. While advances are slowly being realized, stem cells possess huge potential to ameliorate disease and counteract the aging process, causing its speculation as the next panacea. Amidst public pressure to advance rapidly to clinical trials, there is a need to understand the biology of stem cells and to support basic research programs. Without a proper comprehension of how cells and tissues are maintained during the adult life span, clinical trials are bound to fail. This review will cover the basic biology of stem cells, the various types of stem cells, their potential function, and the advantages and disadvantages to their use in medicine. We will next cover the role of G-protein coupled receptors in the regulation of stem cells and their potential in future clinical applications. PMID:23415095

  1. Stem cell therapy without the cells

    PubMed Central

    Maguire, Greg

    2013-01-01

    As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.3 That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment. PMID:24567776

  2. Microbioreactors for Stem Cell Research

    NASA Astrophysics Data System (ADS)

    Freytes, Donald O.; Vunjak-Novakovic, Gordana

    During tissue development and regeneration, stem cells respond to the entire milieu of their environment, through dynamic interactions with the surrounding cells, extracellular matrix, and cascades of molecular and physical regulatory factors. A new generation of culture systems is emerging to offer some of the biological fidelity of a whole organism within highly controllable in vitro settings and provide the cultured cells with the combinations of factors they normally encounter in vivo. There is a growing notion that such "biomimetic" systems are essential for unlocking the full potential of stem cells - for tissue regeneration as well as biological research. In this chapter, we discuss the biological principles for designing biologically inspired culture systems for stem cell research and focus on the control of stem cell microenvironment through surface patterning, microfluidics, and electrical stimulation.

  3. Molecular Evolution of Drosophila Germline Stem Cell and Neural Stem Cell Regulating Genes

    PubMed Central

    Choi, Jae Young; Aquadro, Charles F.

    2015-01-01

    Here, we study the molecular evolution of a near complete set of genes that had functional evidence in the regulation of the Drosophila germline and neural stem cell. Some of these genes have previously been shown to be rapidly evolving by positive selection raising the possibility that stem cell genes as a group have elevated signatures of positive selection. Using recent Drosophila comparative genome sequences and population genomic sequences of Drosophila melanogaster, we have investigated both long- and short-term evolution occurring across these two different stem cell systems, and compared them with a carefully chosen random set of genes to represent the background rate of evolution. Our results showed an excess of genes with evidence of a recent selective sweep in both germline and neural stem cells in D. melanogaster. However compared with their control genes, both stem cell systems had no significant excess of genes with long-term recurrent positive selection in D. melanogaster, or across orthologous sequences from the melanogaster group. The evidence of long-term positive selection was limited to a subset of genes with specific functions in both the germline and neural stem cell system. PMID:26507797

  4. MicroRNAs as novel regulators of stem cell fate

    PubMed Central

    Choi, Eunhyun; Choi, Eunmi; Hwang, Ki-Chul

    2013-01-01

    Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineage-specific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineage-specific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells. Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted. PMID:24179605

  5. PRIMITIVE ADULT HEMATOPOIETIC STEM CELLS CAN FUNCTION AS OSTEOBLAST PRECURSORS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hem...

  6. Stem Cells in the Lung

    PubMed Central

    Liu, Xiaoming; Driskell, Ryan R.; Engelhardt, John F.

    2007-01-01

    The lung is composed of two major anatomically distinct regions—the conducting airways and gas-exchanging airspaces. From a cell biology standpoint, the conducting airways can be further divided into two major compartments, the tracheobronchial and bronchiolar airways, while the alveolar regions of the lung make up the gas-exchanging airspaces. Each of these regions consists of distinct epithelial cell types with unique cellular physiologies and stem cell compartments. This chapter focuses on model systems with which to study stem cells in the adult tracheobronchial airways, also referred to as the proximal airway of the lung. Important in such models is an appreciation for the diversity of stem cell niches in the conducting airways that provide localized environmental signals to both maintain and mobilize stem cells in the setting of airway injury and normal cellular turnover. Because cellular turnover in airways is relatively slow, methods for analysis of stem cells in vivo have required prior injury to the lung. In contrast, ex vivo and in vitro models for analysis of airway stem cells have used genetic markers to track lineage relationships together with reconstitution systems that mimic airway biology. Over the past decades, several widely acceptable methods have been developed and used in the characterization of adult airway stem/ progenitor cells. These include localization of label-retaining cells (LRCs), retroviral tagging of epithelial cells seeded into xenografts, air–liquid interface cultures to track clonal proliferative potential, and multiple transgenic mouse models. This chapter reviews the biologic context and use of these models while providing detailed methods for several of the more broadly useful models for studying adult airway stem/progenitor cell types. PMID:17141060

  7. Dispelling Stem-Cell Ideology.

    PubMed

    Shrader-Frechette, Kristin

    2016-05-01

    Week-old embryos are considered the richest source of stem cells usable in medical treatments. Because the embryos are destroyed when the stem cells are removed, the debate over the embryo's legal, moral, political, and scientific status has exploded. In this debate, Sheldon Krimsky's Stem Cell Dialogues: A Philosophical and Scientific Inquiry into Medical Frontiers (Columbia UP, 2015) is the single best book. Evenhanded, eminently readable, up to date, educational, scientifically precise, powerfully researched, and very entertaining, Krimsky's slim volume is one that no scientist, policy-maker, ethicist, or intelligent reader should miss. PMID:27150419

  8. Harvesting dental stem cells - Overview.

    PubMed

    Sunil, P M; Manikandan, Ramanathan; Muthumurugan; Yoithapprabhunath, Thukanayakanpalayam Ragunathan; Sivakumar, Muniapillai

    2015-08-01

    Dental stem cells have recently become one of the widely researched areas in dentistry. Ever since the identification of stem cells from various dental tissues like deciduous teeth, dental papilla, periodontal ligament and third molars, storing them for future use for various clinical applications was being explored. Dental stem cells were harvested and isolated using various techniques by different investigators and laboratories. This article explains the technical aspects of preparing the patient, atraumatic and aseptic removal of the tooth and its safe transportation and preservation for future expansion. PMID:26538883

  9. Microarrayed Materials for Stem Cells

    PubMed Central

    Mei, Ying

    2013-01-01

    Stem cells hold remarkable promise for applications in disease modeling, cancer therapy and regenerative medicine. Despite the significant progress made during the last decade, designing materials to control stem cell fate remains challenging. As an alternative, materials microarray technology has received great attention because it allows for high throughput materials synthesis and screening at a reasonable cost. Here, we discuss recent developments in materials microarray technology and their applications in stem cell engineering. Future opportunities in the field will also be reviewed. PMID:24311967

  10. Stem cells, dot-com.

    PubMed

    Liang, Bryan A; Mackey, Tim K

    2012-09-12

    Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of stem cells is subject to drugs or biologics regulations. To address this gap, regulatory agencies should be given clear authority, and the international community should create a framework for appropriate stem cell use. In addition, consumer protection laws should be used to scrutinize providers. PMID:22972840

  11. Harvesting dental stem cells - Overview

    PubMed Central

    Sunil, P. M.; Manikandan, Ramanathan; Muthumurugan; Yoithapprabhunath, Thukanayakanpalayam Ragunathan; Sivakumar, Muniapillai

    2015-01-01

    Dental stem cells have recently become one of the widely researched areas in dentistry. Ever since the identification of stem cells from various dental tissues like deciduous teeth, dental papilla, periodontal ligament and third molars, storing them for future use for various clinical applications was being explored. Dental stem cells were harvested and isolated using various techniques by different investigators and laboratories. This article explains the technical aspects of preparing the patient, atraumatic and aseptic removal of the tooth and its safe transportation and preservation for future expansion. PMID:26538883

  12. Bone marrow-derived stem cells and radiation response.

    PubMed

    Greenberger, Joel S; Epperly, Michael

    2009-04-01

    The recovery of tissues and organs from ionizing irradiation is critically dependent on the repopulation of resident stem cells, defined as the subset of cells with capacity for both self-renewal and differentiation. Stem cells of both hematopoietic and epithelial origin reside in defined areas of the cellular microenvironment (recently defined as the stem cell "niche"). Experiments using serial repopulation assays in serial generations of total body irradiated mice receiving transplanted marrow and in continuous bone marrow cultures both identified specific microanatomic sites that comprise the bone marrow stem cell niche. Supportive cells of the hematopoietic microenvironment not only contribute to stem cell repopulation capacity but also to the maintenance of their quiescent or nonproliferative state, which allows the most primitive hematopoietic stem cells to stay in a noncycling state protected from both direct ionizing radiation-induced cell-cycle phase-specific killing and indirect cytokine and free radical mediated killing. Recent evidence has defined both cell contact and humoral mechanisms of protection of hematopoietic stem cells by stromal cells. There is also recent evidence for multilineage differentiation capacity of cells of the hematopoietic microenvironment termed bone marrow stromal cells (mesenchymal stem cells). Both hematopoietic stem cells and mesenchymal stem cell populations have been shown to be involved in the repair of ionizing irradiation damage of distant epithelial as well as other hematopoietic sites through their capacity to migrate through the circulation. The radiobiology of these 2 bone marrow stem cell populations is the subject of intense investigation. This review defines the status of research in the areas of stem cell quiescence, niche contact, and migratory responses to ionizing irradiation. PMID:19249651

  13. 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

  14. Mesenchymal stem cells as feeder cells for pancreatic islet transplants.

    PubMed

    Sordi, Valeria; Piemonti, Lorenzo

    2010-01-01

    Allogeneic islet transplantation serves as a source of insulin-secreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients. PMID:21060972

  15. Stem cell therapy independent of stemness.

    PubMed

    Lee, Techung

    2012-12-26

    Mesenchymal stem cell (MSC) therapy is entering a new era shifting the focus from initial feasibility study to optimization of therapeutic efficacy. However, how MSC therapy facilitates tissue regeneration remains incompletely characterized. Consistent with the emerging notion that secretion of multiple growth factors/cytokines (trophic factors) by MSC provides the underlying tissue regenerative mechanism, the recent study by Bai et al demonstrated a critical therapeutic role of MSC-derived hepatocyte growth factor (HGF) in two animal models of multiple sclerosis (MS), which is a progressive autoimmune disorder caused by damage to the myelin sheath and loss of oligodendrocytes. Although current MS therapies are directed toward attenuation of the immune response, robust repair of myelin sheath likely requires a regenerative approach focusing on long-term replacement of the lost oligodendrocytes. This approach appears feasible because adult organs contain various populations of multipotent resident stem/progenitor cells that may be activated by MSC trophic factors as demonstrated by Bai et al This commentary highlights and discusses the major findings of their studies, emphasizing the anti-inflammatory function and trophic cross-talk mechanisms mediated by HGF and other MSC-derived trophic factors in sustaining the treatment benefits. Identification of multiple functionally synergistic trophic factors, such as HGF and vascular endothelial growth factor, can eventually lead to the development of efficacious cell-free therapeutic regimens targeting a broad spectrum of degenerative conditions. PMID:23516128

  16. Novel insights in basic and applied stem cell therapy.

    PubMed

    Siniscalco, Dario; Giordano, Antonio; Galderisi, Umberto

    2012-05-01

    The achievement of novel findings in stem cell research were the subject of the meeting organized by Stem Cell Research Italy (SCR Italy) and by the International Society for Cellular Therapy-Europe (ISCT). Stem cell therapy represents great promise for the future of molecular and regenerative medicine. The use of several types of stem cells is a real opportunity to provide a valid approach to curing several untreatable human diseases. Before it is suitable for clinical applications, stem cell biology needs to be investigated further and in greater detail. Basic stem cell research could provide exact knowledge regarding stem cell action mechanisms, and pre-clinical research on stem cells on an in vivo model of disease provides scientific evidence for future human applications. Applied stem cell research is a promising new approach to handling several diseases. Along with tissue engineering, it offers a new and promising discipline that can help to manage human pathologies through stem cell therapy. All of these themes were discussed in this meeting, covering stem cell subtypes with their newest basic and applied research. PMID:21780112

  17. Stem cells and cancer: an overview.

    PubMed

    Sales, Kevin M; Winslet, Marc C; Seifalian, Alexander M

    2007-12-01

    Definite evidence of the importance of cancer stem cells in the progression of cancer has now come to light. Key markers of these cells have been identified in many solid tumours as well as leukaemias. Specific studies modelling the tumour induction of specific cells isolated by surface antigens such as CD44 have demonstrated that these cells are not only present in tumours but that they are the key units in their tumourgenecity. These findings provide useful insight for disease progression, treatment and metastasis. The wide variety of proposed markers, and their similarity to endothelial progenitor cells found in angiogenesis, complicates these studies. Definite proof falls only in the induction of tumours in vivo. Here we review the developments in cancer stem cells and the markers that have been found for these cells. PMID:17955391

  18. Bone marrow (stem cell) donation

    MedlinePlus

    Stem cell transplant; Allogeneic-donation ... There are two types of bone marrow donation: Autologous bone marrow transplant is when people donate their own bone marrow. "Auto" means self. Allogenic bone marrow transplant is when another person ...

  19. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  20. Review: Corneal epithelial stem cells, their niche and wound healing

    PubMed Central

    2013-01-01

    Stem cells emerged as a concept during the second half of 19th century, first as a theoretical entity, but then became one of the most promising research fields in cell biology. This work describes the most important characteristics of adult stem cells, including the experimental criteria used to identify them, and discusses current knowledge that led to the proposal that stem cells existed in different parts of the eye, such as the retina, lens, conjunctiva, corneal stroma, Descemet’s membrane, and the subject of this review: the corneal epithelium. Evidence includes results that support the presence of corneal epithelial stem cells at the limbus, as well as the major obstacles to isolating them as pure cell populations. Part of this review describes the variation in the basement membrane composition between the limbus and the central cornea, to show the importance of the corneal stem cell niche, its structure, and the participation of extracellular matrix (ECM) components in regulating corneal stem cell compartment. Results obtained by various laboratories suggest that the extracellular matrix plays a central role in regulating stem cell commitment, corneal differentiation, and participation in corneal wound healing, in addition to other environmental signals such as cytokines and growth factors. The niche could define cell division patterns in corneal stem cell populations, establishing whether stem cells divide asymmetrically or symmetrically. Characterization and understanding of the factors that regulate corneal epithelial stem cells should open up new paths for developing new therapies and strategies for accelerating and improving corneal wound healing. PMID:23901244

  1. Intravenous transplantation of mesenchymal stem cells preconditioned with early phase stroke serum: current evidence and study protocol for a randomized trial

    PubMed Central

    2013-01-01

    Background Recovery after a major stroke is usually limited, but cell therapy for patients with fixed neurologic deficits is emerging. Several recent clinical trials have investigated mesenchymal stem cell (MSC) therapy for patients with ischemic stroke. We previously reported the results of a controlled trial on the application of autologous MSCs in patients with ischemic stroke with a long-term follow-up of up to 5 years (the 'STem cell Application Researches and Trials In NeuroloGy’ (STARTING) study). The results from this pilot trial are challenging, but also raise important issues. In addition, there have been recent efforts to improve the safety and efficacy of MSC therapy for stroke. Methods and design The clinical and preclinical background and the STARTING-2 study protocol are provided. The trial is a prospective, randomized, open-label, blinded-endpoint (PROBE) clinical trial. Both acute and chronic stroke patients will be selected based on clinical and radiological features and followed for 3 months after MSC treatment. The subjects will be randomized into one of two groups: (A) a MSC group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be intravenously administered after ex vivo culture expansion with autologous ischemic serum obtained as early as possible, to enhance the therapeutic efficacy (ischemic preconditioning). Objective outcome measurements will be performed using multimodal MRI and detailed functional assessments by blinded observers. Discussion This trial is the first to evaluate the efficacy of MSCs in patients with ischemic stroke. The results may provide better evidence for the effectiveness of MSC therapy in patients with ischemic stroke. Trial registration This trial was registered with ClinicalTrials.gov, number NCT01716481. PMID:24083670

  2. Pancreatic Stem Cells Remain Unresolved

    PubMed Central

    Morahan, Grant

    2014-01-01

    Diabetes mellitus is caused by absolute (type 1) or relative (type 2) deficiency of insulin-secreting islet β cells. An ideal treatment of diabetes would, therefore, be to replace the lost or deficient β cells, by transplantation of donated islets or differentiated endocrine cells or by regeneration of endogenous islet cells. Due to their ability of unlimited proliferation and differentiation into all functional lineages in our body, including β cells, embryonic stem cells and induced pluripotent stem cells are ideally placed as cell sources for a diabetic transplantation therapy. Unfortunately, the inability to generate functional differentiated islet cells from pluripotent stem cells and the poor availability of donor islets have severely restricted the broad clinical use of the replacement therapy. Therefore, endogenous sources that can be directed to becoming insulin-secreting cells are actively sought after. In particular, any cell types in the developing or adult pancreas that may act as pancreatic stem cells (PSC) would provide an alternative renewable source for endogenous regeneration. In this review, we will summarize the latest progress and knowledge of such PSC, and discuss ways that facilitate the future development of this often controversial, but crucial research. PMID:25132582

  3. Autologous stem cells for personalised medicine.

    PubMed

    Prasongchean, Weerapong; Ferretti, Patrizia

    2012-09-15

    Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention. PMID:22561284

  4. 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

  5. Large animal models for stem cell therapy

    PubMed Central

    2013-01-01

    The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions

  6. Plasticity of spermatogonial stem cells.

    PubMed

    Cooke, Paul S; Simon, Liz; Nanjappa, Manjunatha K; Medrano, Theresa I; Berry, Suzanne E

    2015-01-01

    There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs), and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES) cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine. PMID:25677134

  7. Plasticity of spermatogonial stem cells

    PubMed Central

    Cooke, Paul S; Simon, Liz; Nanjappa, Manjunatha K; Medrano, Theresa I; Berry, Suzanne E

    2015-01-01

    There have been significant breakthroughs over the past decade in the development and use of pluripotent stem cells as a potential source of cells for applications in regenerative medicine. It is likely that this methodology will begin to play an important role in human clinical medicine in the years to come. This review describes the plasticity of one type of pluripotent cell, spermatogonial stem cells (SSCs), and their potential therapeutic applications in regenerative medicine and male infertility. Normally, SSCs give rise to sperm when in the testis. However, both human and murine SSCs can give rise to cells with embryonic stem (ES) cell-like characteristics that can be directed to differentiate into tissues of all three embryonic germ layers when placed in an appropriate inductive microenvironment, which is in contrast to other postnatal stem cells. Previous studies have reported that SSCs expressed an intermediate pluripotent phenotype before differentiating into a specific cell type and that extended culture was necessary for this to occur. However, recent studies from our group using a tissue recombination model demonstrated that SSCs differentiated rapidly into another tissue, in this case, prostatic epithelium, without expression of pluripotent ES cell markers before differentiation. These results suggest that SSCs are capable of directly differentiating into other cell types without going through an intermediate ES cell-like stage. Because SSCs do not require reprogramming to achieve a pluripotent state, they are an attractive source of pluripotent cells for use in regenerative medicine. PMID:25677134

  8. Stem cell isolation: Differential stickiness

    NASA Astrophysics Data System (ADS)

    Abilez, Oscar J.; Wu, Joseph C.

    2013-06-01

    Technologies to isolate colonies of human pluripotent stem cells from other cell types in a high-throughput manner are lacking. A microfluidic-based approach that exploits differences in the adhesion strength between these cells and a substrate may soon fill the gap.

  9. Reprogrammed pluripotent stem cells from somatic cells.

    PubMed

    Kim, Jong Soo; Choi, Hyun Woo; Choi, Sol; Do, Jeong Tae

    2011-06-01

    Pluripotent stem cells, such as embryonic stem (ES) cells, can differentiate into all cell types. So, these cells can be a biological resource for regenerative medicine. However, ES cells known as standard pluripotent cells have problem to be used for cell therapy because of ethical issue of the origin and immune response on the graft. Hence, recently reprogrammed pluripotent cells have been suggested as an alternative source for regenerative medicine. Somatic cells can acquire the ES cell-like pluripotency by transferring somatic cell nuclei into oocytes, by cell fusion with pluripotent cells. Retroviral-mediated introduction of four factors, Oct4, Sox2, Klf4 and c-Myc can successfully reprogram somatic cells into ES cell-like pluripotent stem cells, known as induced pluripotent stem (iPS) cells. These cells closely resemble ES cells in gene expression pattern, cell biologic and phenotypic characteristics. However, to reach the eventual goal of clinical application, it is necessary to overcome the major drawbacks such as low reprogramming efficiency and genomic alterations due to viral integration. In this review, we discuss the current reprogramming techniques and mechanisms of nuclear reprogramming induced by transcription factor transduction. PMID:24298328

  10. Generation of induced pluripotent stem cells from the pig

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The value of stem cells has become increasingly evident in recent years with the advent of genetic engineering tools that allow site-specific modifications to the genome. The use of stem cells to induce modifications has several potential benefits for the livestock industry including improving anim...

  11. 25 YEARS OF EPIDERMAL STEM CELLS

    PubMed Central

    Ghadially, Ruby

    2012-01-01

    This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The last 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell biology is discussed in this article. The challenges we still face in understanding epidermal stem cell include defining molecular markers for stem and progenitor subpopulations, determining the locations and contributions of the different stem cell niches, and mapping regulatory pathways of epidermal stem cell proliferation and differentiation. However, our rapidly evolving understanding of epidermal stem cells has many potential uses that promise to translate into improved patient therapy. PMID:22205306

  12. Neural stem cells: plasticity and their transdifferentiation potential.

    PubMed

    Vescovi, Angelo; Gritti, Angela; Cossu, Giulio; Galli, Rossella

    2002-01-01

    The presence of resident stem cells in adult tissues is of fundamental importance for the maintenance of their structural and functional integrity. In fact, throughout life, somatic stem cells attend to the critical function of substituting terminally differentiated cells lost to physiological turnover, injury or disease. Thence, one of the basic dogmata in tissue biology holds that the differentiation potential of an adult stem cell is restricted to the generation of the mature cell lineages found in the tissue to which the stem cell belongs. A plethora of recent evidences from many groups, including ours, is now providing evidence that adult stem cells may possess a broader differentiation repertoire than expected and that their fate potential may not be as tissue specific as once thought. The initial example of an unforeseen, trans-germ layer plasticity - that seems now to emerge as a prototypic functional trait of various somatic stem cells of different origin - has come from the reported awakening of a latent hemopoietic developmental capacity in stem cells isolated from the adult mammalian brain following their transplantation into sub-lethally irradiated mice. More recently, it has been shown that adult neural stem cells can differentiate into a wide array of bodily cells of different origin when injected into the blastocyst and into myogenic cells when transplanted into the adult regenerating skeletal muscle. Moreover, bone marrow stem cells can now give rise to skeletal muscle, hepatic and brain cells, whereas muscle precursors can generate blood cells. In this article, we review some of the basic notions regarding the functional properties of the adult neural stem cells and discuss findings in the expanding area of trans-germ layer conversion, with emphasis on the neural stem cell. PMID:12021492

  13. Engineering stem cell niches in bioreactors

    PubMed Central

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering. PMID:24179601

  14. Stem cell regulation: Implications when differentiated cells regulate symmetric stem cell division.

    PubMed

    Høyem, Marte Rørvik; Måløy, Frode; Jakobsen, Per; Brandsdal, Bjørn Olav

    2015-09-01

    We use a mathematical model to show that if symmetric stem cell division is regulated by differentiated cells, then changes in the population dynamics of the differentiated cells can lead to changes in the population dynamics of the stem cells. More precisely, the relative fitness of the stem cells can be affected by modifying the death rate of the differentiated cells. This result is interesting because stem cells are less sensitive than differentiated cells to environmental factors, such as medical therapy. Our result implies that stem cells can be manipulated indirectly by medical treatments that target the differentiated cells. PMID:25997796

  15. Stacking the DEK: From chromatin topology to cancer stem cells

    PubMed Central

    Privette Vinnedge, Lisa M.; Kappes, Ferdinand; Nassar, Nicolas; Wells, Susanne I.

    2013-01-01

    Stem cells are essential for development and tissue maintenance and display molecular markers and functions distinct from those of differentiated cell types in a given tissue. Malignant cells that exhibit stem cell-like activities have been detected in many types of cancers and have been implicated in cancer recurrence and drug resistance. Normal stem cells and cancer stem cells have striking commonalities, including shared cell surface markers and signal transduction pathways responsible for regulating quiescence vs. proliferation, self-renewal, pluripotency and differentiation. As the search continues for markers that distinguish between stem cells, progenitor cells and cancer stem cells, growing evidence suggests that a unique chromatin-associated protein called DEK may confer stem cell-like qualities. Here, we briefly describe current knowledge regarding stem and progenitor cells. We then focus on new findings that implicate DEK as a regulator of stem and progenitor cell qualities, potentially through its unusual functions in the regulation of local or global chromatin organization. PMID:23255114

  16. Stem cell therapies for treating osteoarthritis: prescient or premature?

    PubMed

    Whitworth, Deanne J; Banks, Tania A

    2014-12-01

    There has been unprecedented interest in recent years in the use of stem cells as therapy for an array of diseases in companion animals. Stem cells have already been deployed therapeutically in a number of clinical settings, in particular the use of mesenchymal stem cells to treat osteoarthritis in horses and dogs. However, an assessment of the scientific literature highlights a marked disparity between the purported benefits of stem cell therapies and their proven abilities as defined by rigorously controlled scientific studies. Although preliminary data generated from clinical trials in human patients are encouraging, therapies currently available to treat animals are supported by very limited clinical evidence, and the commercialisation of these treatments may be premature. This review introduces the three main types of stem cells relevant to veterinary applications, namely, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells, and draws together research findings from in vitro and in vivo studies to give an overview of current stem cell therapies for the treatment of osteoarthritis in animals. Recent advances in tissue engineering, which is proposed as the future direction of stem cell-based therapy for osteoarthritis, are also discussed. PMID:25457267

  17. Histone Deacetylase Inhibition with Valproic Acid Downregulates Osteocalcin Gene Expression in Human Dental Pulp Stem Cells and Osteoblasts: Evidence for HDAC2 Involvement

    PubMed Central

    Paino, Francesca; la Noce, Marcel; Tirino, Virginia; Naddeo, Pasqualina; Desiderio, Vincenzo; Pirozzi, Giuseppe; De Rosa, Alfredo; Laino, Luigi; Altucci, Lucia; Papaccio, Gianpaolo

    2014-01-01

    Adult mesenchymal stem cells, such as dental pulp stem cells, are of great interest for cell-based tissue engineering strategies because they can differentiate into a variety of tissue-specific cells, above all, into osteoblasts. In recent years, epigenetic studies on stem cells have indicated that specific histone alterations and modifying enzymes play essential roles in cell differentiation. However, although several studies have reported that valproic acid (VPA)—a selective inhibitor of histone deacetylases (HDAC)—enhances osteoblast differentiation, data on osteocalcin expression—a late-stage marker of differentiation—are limited. We therefore decided to study the effect of VPA on dental pulp stem cell differentiation. A low concentration of VPA did not reduce cell viability, proliferation, or cell cycle profile. However, it was sufficient to significantly enhance matrix mineralization by increasing osteopontin and bone sialoprotein expression. In contrast, osteocalcin levels were decreased, an effect induced at the transcriptional level, and were strongly correlated with inhibition of HDAC2. In fact, HDAC2 silencing with shRNA produced a similar effect to that of VPA treatment on the expression of osteoblast-related markers. We conclude that VPA does not induce terminal differentiation of osteoblasts, but stimulates the generation of less mature cells. Moreover, specific suppression of an individual HDAC by RNA interference could enhance only a single aspect of osteoblast differentiation, and thus produce selective effects. PMID:24105979

  18. Stem cell therapy: from evidence-based medicine to emotion-based medicine? The long Italian way for a scientific regulation

    PubMed Central

    2013-01-01

    On 23 May 2013, the Italian health minister decided to endorse a law regarding controversial stem cell-based therapies in 32 young terminally ill patients, shocking many scientists. According to the international scientific community, these therapies could be dangerous because they were not rigorously tested in humans. This decision was made after many days of media and judiciary pressure. Several lawsuits regarding stem cell-based therapies were brought before the judiciary districts of different Italian regions. We analyzed the Italian legal context regarding the field of pharmaceutical and medical devices, including the European Union trend. A national database - commonly used to manage legal materials for professional or educational purposes or both - was used to find relevant legal cases involving stem cell-based therapies. Stem cell-based therapies endorsed by the new Italian law have been the subject of an important discussion not only in the scientific community but also in various courts. We found several legal actions filed by parents in order to make stem cells available to their young children, who had serious neurodegenerative diseases. The majority of the analyzed legal disputes were settled in favor of the applicants, whereas only two decisions (Courts of Justice of Rome and Florence) rejected the complaint because of the absence of sufficient scientific data regarding stem cell-based therapies. The present Italian situation is influencing the destiny of future young patients and strongly impacting public and institutional opinion. It is a practical example of the complexity of the decision of not providing unapproved scientific stem cell-based therapies when medicine does not have any other alternative therapies. PMID:24456690

  19. Stem cell therapy: from evidence-based medicine to emotion-based medicine? The long Italian way for a scientific regulation.

    PubMed

    Frati, Paola; Frati, Giacomo; Gulino, Matteo; Montanari Vergallo, Gianluca; Di Luca, Alessandro; Fineschi, Vittorio

    2013-01-01

    On 23 May 2013, the Italian health minister decided to endorse a law regarding controversial stem cell-based therapies in 32 young terminally ill patients, shocking many scientists. According to the international scientific community, these therapies could be dangerous because they were not rigorously tested in humans. This decision was made after many days of media and judiciary pressure. Several lawsuits regarding stem cell-based therapies were brought before the judiciary districts of different Italian regions. We analyzed the Italian legal context regarding the field of pharmaceutical and medical devices, including the European Union trend. A national database - commonly used to manage legal materials for professional or educational purposes or both - was used to find relevant legal cases involving stem cell-based therapies. Stem cell-based therapies endorsed by the new Italian law have been the subject of an important discussion not only in the scientific community but also in various courts. We found several legal actions filed by parents in order to make stem cells available to their young children, who had serious neurodegenerative diseases. The majority of the analyzed legal disputes were settled in favor of the applicants, whereas only two decisions (Courts of Justice of Rome and Florence) rejected the complaint because of the absence of sufficient scientific data regarding stem cell-based therapies. The present Italian situation is influencing the destiny of future young patients and strongly impacting public and institutional opinion. It is a practical example of the complexity of the decision of not providing unapproved scientific stem cell-based therapies when medicine does not have any other alternative therapies. PMID:24456690

  20. Alkaline Phosphatase in Stem Cells

    PubMed Central

    Štefková, Kateřina; Procházková, Jiřina; Pacherník, Jiří

    2015-01-01

    Alkaline phosphatase is an enzyme commonly expressed in almost all living organisms. In humans and other mammals, determinations of the expression and activity of alkaline phosphatase have frequently been used for cell determination in developmental studies and/or within clinical trials. Alkaline phosphatase also seems to be one of the key markers in the identification of pluripotent embryonic stem as well as related cells. However, alkaline phosphatases exist in some isoenzymes and isoforms, which have tissue specific expressions and functions. Here, the role of alkaline phosphatase as a stem cell marker is discussed in detail. First, we briefly summarize contemporary knowledge of mammalian alkaline phosphatases in general. Second, we focus on the known facts of its role in and potential significance for the identification of stem cells. PMID:25767512

  1. Tenascins in stem cell niches.

    PubMed

    Chiquet-Ehrismann, Ruth; Orend, Gertraud; Chiquet, Matthias; Tucker, Richard P; Midwood, Kim S

    2014-07-01

    Tenascins are extracellular matrix proteins with distinct spatial and temporal expression during development, tissue homeostasis and disease. Based on their expression patterns and knockout phenotypes an important role of tenascins in tissue formation, cell adhesion modulation, regulation of proliferation and differentiation has been demonstrated. All of these features are of importance in stem cell niches where a precise regulation of growth versus differentiation has to be guaranteed. In this review we summarize the expression and possible functions of tenascins in neural, epithelial and osteogenic stem cell niches during normal development and organ turnover, in the hematopoietic and pro-inflammatory niche as well as in the metastatic niche during cancer progression. PMID:24472737

  2. Hematopoietic stem cells: multiparameter regulation.

    PubMed

    Song, Kedong; Li, Liying; Wang, Yiwei; Liu, Tianqing

    2016-04-01

    Hematopoietic stem cells (HSCs) are capable to self-renew with multi-potency which generated much excitement in clinical therapy. However, the main obstacle of HSCs in clinical application was insufficient number of HSCs which were derived from either bone marrow, peripheral blood or umbilical cord blood. This review briefly discusses the indispensable utility of growth factors and cytokines, stromal cells, extracellular matrix, bionic scaffold and microenvironment aiming to control the hematopoiesis in all directions and provide a better and comprehensive understanding for in vitro expansion of hematopoietic stem cells. PMID:26883144

  3. Stem cells: sources and therapies.

    PubMed

    Monti, Manuela; Perotti, Cesare; Del Fante, Claudia; Cervio, Marila; Redi, Carlo Alberto

    2012-01-01

    The historical, lexical and conceptual issues embedded in stem cell biology are reviewed from technical, ethical, philosophical, judicial, clinical, economic and biopolitical perspectives. The mechanisms assigning the simultaneous capacity to self-renew and to differentiate to stem cells (immortal template DNA and asymmetric division) are evaluated in the light of the niche hypothesis for the stemness state. The induction of cell pluripotency and the different stem cells sources are presented (embryonic, adult and cord blood). We highlight the embryonic and adult stem cell properties and possible therapies while we emphasize the particular scientific and social values of cord blood donation to set up cord blood banks. The current scientific and legal frameworks of cord blood banks are reviewed at an international level as well as allogenic, dedicated and autologous donations. The expectations and the challenges in relation to present-day targeted diseases like diabetes mellitus type I, Parkinson's disease and myocardial infarction are evaluated in the light of the cellular therapies for regenerative medicine. PMID:23283430

  4. Glioblastoma stem cells and stem cell-targeting immunotherapies.

    PubMed

    Esparza, Rogelio; Azad, Tej D; Feroze, Abdullah H; Mitra, Siddhartha S; Cheshier, Samuel H

    2015-07-01

    Advancements in immunotherapeutics promise new possibilities for the creation of glioblastoma (GBM) treatment options. Ongoing work in cancer stem cell biology has progressively elucidated the role of this tumor sub-population in oncogenesis and has distinguished them as prime therapeutic targets. Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, we believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM. PMID:25682090

  5. Human stem cell ethics: beyond the embryo.

    PubMed

    Sugarman, Jeremy

    2008-06-01

    Human embryonic stem cell research has elicited powerful debates about the morality of destroying human embryos. However, there are important ethical issues related to stem cell research that are unrelated to embryo destruction. These include particular issues involving different types of cells used, the procurement of such cells, in vivo use of stem cells, intellectual property, and conflicts of interest. PMID:18522846

  6. Stem-cell ecology and stem cells in motion

    PubMed Central

    Scadden, David T.

    2008-01-01

    This review highlights major scientific developments over the past 50 years or so in concepts related to stem-cell ecology and to stem cells in motion. Many thorough and eloquent reviews have been presented in the last 5 years updating progress in these issues. Some paradigms have been challenged, others validated, or new ones brought to light. In the present review, we will confine our remarks to the historical development of progress. In doing so, we will refrain from a detailed analysis of controversial data, emphasizing instead widely accepted views and some challenging novel ones. PMID:18398055

  7. Common stemness regulators of embryonic and cancer stem cells

    PubMed Central

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. PMID:26516408

  8. Stem cell mechanobiology: diverse lessons from bone marrow.

    PubMed

    Ivanovska, Irena L; Shin, Jae-Won; Swift, Joe; Discher, Dennis E

    2015-09-01

    A stem cell niche is defined by various chemical and physical features that influence whether a stem cell remains quiescent, divides, or differentiates. We review mechanical determinants that affect cell fate through actomyosin forces, nucleoskeleton remodeling, and mechanosensitive translocation of transcription factors. Current methods for physical characterization of tissue microenvironments are summarized together with efforts to recapitulate niche mechanics in culture. We focus on mesenchymal stem cells, particularly in osteogenesis and adipogenesis, and on blood stem cells - both of which reside in mechanically diverse marrow microenvironments. Given the explosion of efforts with pluripotent stem cells, the evident mechanosensitivity of clinically relevant, multipotent marrow cells underscores an increasing need to examine and understand in vivo and in vitro physical properties on length scales that cells sense. PMID:26045259

  9. Immunohistological techniques for studying the Drosophila male germline stem cell.

    PubMed

    Singh, Shree Ram; Hou, Steven X

    2008-01-01

    Stem cells are undifferentiated cells that have a remarkable ability to self-renew and produce differentiated cells that support normal development and tissue homeostasis. This unique capacity makes stem cells a powerful tool for future regenerative medicine and gene therapy. Accumulative evidence suggests that stem cell self-renewal or differentiation is controlled by both intrinsic and extrinsic factors, and that deregulation of stem cell behavior results in cancer formation, tissue degeneration, and premature aging. The Drosophila testis provides an excellent in vivo model for studying and understanding the fundamental cellular and molecular mechanisms controlling stem cell behavior and the relationship between niches and stem cells. At the tip of the Drosophila testes, germline stem cells (GSCs) and somatic stem cells (SSCs) contact each other and share common niches (known as a hub) to maintain spermatogenesis. Signaling pathways, such as the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), bone morphogenetic protein (BMP), ras-associated protein-guanine nucleotide exchange factor for small GTPase (Rap-GEF), and epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK), are known to regulate self-renewal or differentiation of Drosophila male germline stem cells. We describe the detailed in vivo immunohistological protocols that mark GSCs, SSCs, and their progeny in Drosophila testes. PMID:18370050

  10. Molecular Culprits Generating Brain Tumor Stem Cells

    PubMed Central

    Oh, Se-Yeong

    2013-01-01

    Despite current advances in multimodality therapies, such as surgery, radiotherapy, and chemotherapy, the outcome for patients with high-grade glioma remains fatal. Understanding how glioma cells resist various therapies may provide opportunities for developing new therapies. Accumulating evidence suggests that the main obstacle for successfully treating high-grade glioma is the existence of brain tumor stem cells (BTSCs), which share a number of cellular properties with adult stem cells, such as self-renewal and multipotent differentiation capabilities. Owing to their resistance to standard therapy coupled with their infiltrative nature, BTSCs are a primary cause of tumor recurrence post-therapy. Therefore, BTSCs are thought to be the main glioma cells representing a novel therapeutic target and should be eliminated to obtain successful treatment outcomes. PMID:24904883

  11. Cell adhesion in regulation of asymmetric stem cell division

    PubMed Central

    Yamashita, Yukiko M.

    2010-01-01

    Adult stem cells inevitably communicate with their cellular neighbors within the tissues they sustain. Indeed, such communication, particularly with components of the stem cell niche, is essential for many aspects of stem cell behavior, including the maintenance of stem cell identity and asymmetric cell division. Cell adhesion mediates this communication by placing stem cells in close proximity to the signaling source and by providing a polarity cue that orients stem cells. Here, I review the recent discovery that cell adhesion molecules govern the behavior of stem cells. PMID:20724132

  12. Stem Cell Transplantation for Neuroprotection in Stroke

    PubMed Central

    Shinozuka, Kazutaka; Dailey, Travis; Tajiri, Naoki; Ishikawa, Hiroto; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies, we discuss studies that demonstrate effective dose, timing, and route of stem cells. We recognize that stem cell derivations also provide uniquely individual difficulties and limitations in their therapeutic applications. This review will outline the current knowledge, including benefits and challenges, of the many current sources of stem cells for stroke therapy. PMID:24147217

  13. Cancer Stem Cells in Pancreatic Cancer

    PubMed Central

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  14. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  15. Stem cells sources for intervertebral disc regeneration.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  16. Stem Cells in the Limbal Stroma.

    PubMed

    Funderburgh, James L; Funderburgh, Martha L; Du, Yiqin

    2016-04-01

    The corneal stroma contains a population of mesenchymal cells subjacent to the limbal basement membrane with characteristics of adult stem cells. These 'niche cells' support limbal epithelial stem cell viability. In culture by themselves, the niche cells display a phenotype typical of mesenchymal stem cells. These stromal stem cells exhibit a potential to differentiate to multiple cell types, including keratocytes, thus providing an abundant source of these rare cells for experimental and bioengineering applications. Stromal stem cells have also shown the ability to remodel pathological stromal tissue, suppressing inflammation and restoring transparency. Because stromal stem cells can be obtained by biopsy, they offer a potential for autologous stem cell treatment for stromal opacities. This review provides an overview of the status of work on this interesting cell population. PMID:26804252

  17. Leydig cells: From stem cells to aging.

    PubMed

    Chen, Haolin; Ge, Ren-Shan; Zirkin, Barry R

    2009-07-10

    Leydig cells are the testosterone-producing cells of the testis. The adult Leydig cell population ultimately develops from undifferentiated mesenchymal-like stem cells present in the interstitial compartment of the neonatal testis. Four distinct stages of adult Leydig cell development have been identified and characterized: stem Leydig cells, progenitor Leydig cells, immature Leydig cells and adult Leydig cells. The stem Leydig cells are undifferentiated cells that are capable of indefinite self-renewal, differentiation, and replenishment of the Leydig cell niche. Progenitor Leydig cells are derived from the stem Leydig cells. These spindle-shaped cells are luteinizing hormone (LH) receptor positive, have high mitotic activity, and produce little testosterone but rather testosterone metabolites. The progenitor Leydig cells give rise to immature Leydig cells which are round, contain large amounts of smooth endoplasmic reticulum, and produce some testosterone but also very high levels of testosterone metabolites. A single division of these cells produces adult Leydig cells, which are terminally differentiated cells that produce high levels of testosterone. As men age, serum testosterone levels decline, and this is associated with alterations in body composition, energy level, muscle strength, physical, sexual and cognitive functions, and mood. In the Brown Norway rat, used extensively as a model for male reproductive aging, age-related reductions in serum testosterone result from significant decline in the ability of aged Leydig cells to produce testosterone in response to LH stimulation. This review describes Leydig cell development and aging. Additionally, the molecular mechanisms by which testosterone synthesis declines with aging are discussed. PMID:19481681

  18. The regulatory niche of intestinal stem cells.

    PubMed

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders. PMID:27060879

  19. Adult stem cells and their ability to differentiate.

    PubMed

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue. PMID:16865077

  20. p53, Stem Cells, and Reprogramming

    PubMed Central

    Spike, Benjamin T.; Wahl, Geoffrey M.

    2011-01-01

    p53 is well recognized as a potent tumor suppressor. In its classic role, p53 responds to genotoxic insults by inducing cell cycle exit or programmed cell death to limit the propagation of cells with corrupted genomes. p53 is also implicated in a variety of other cellular processes in which its involvement is less well understood including self-renewal, differentiation, and reprogramming. These activities represent an emerging area of intense interest for cancer biologists, as they provide potential mechanistic links between p53 loss and the stem cell–like cellular plasticity that has been suggested to contribute to tumor cell heterogeneity and to drive tumor progression. Despite accumulating evidence linking p53 loss to stem-like phenotypes in cancer, it is not yet understood how p53 contributes to acquisition of “stemness” at the molecular level. Whether and how stem-like cells confer survival advantages to propagate the tumor also remain to be resolved. Furthermore, although it seems reasonable that the combination of p53 deficiency and the stem-like state could contribute to the genesis of cancers that are refractory to treatment, direct linkages and mechanistic underpinnings remain under investigation. Here, we discuss recent findings supporting the connection between p53 loss and the emergence of tumor cells bearing functional and molecular similarities to stem cells. We address several potential molecular and cellular mechanisms that may contribute to this link, and we discuss implications of these findings for the way we think about cancer progression. PMID:21779509

  1. Mesenchymal stem cells and cardiac repair

    PubMed Central

    Nesselmann, Catharina; Ma, Nan; Bieback, Karen; Wagner, Wolfgang; Ho, Anthony; Konttinen, Yrjö T; Zhang, Hao; Hinescu, Mihail E; Steinhoff, Gustav

    2008-01-01

    Accumulating clinical and experimental evidence indicates that mesenchymal stem cells (MSCs) are promising cell types in the treatment of cardiac dysfunction. They may trigger production of reparative growth factors, replace damaged cells and create an environment that favours endogenous cardiac repair. However, identifying mechanisms which regulate the role of MSCs in cardiac repair is still at work. To achieve the maximal clinical benefits, ex vivo manipulation can further enhance MSC therapeutic potential. This review focuses on the mechanism of MSCs in cardiac repair, with emphasis on ex vivo manipulation. PMID:18684237

  2. Human colonic fibroblasts regulate stemness and chemotherapy resistance of colon cancer stem cells

    PubMed Central

    Colak, S.; Medema, J.P.

    2016-01-01

    abstract There is increasing evidence that cancers are heterogeneous and contain a hierarchical organization consisting of cancer stem cells and their differentiated cell progeny. These cancer stem cells are at the core of the tumor as they represent the clonogenic cells within a tumor. Moreover, these cells are considered to contain selective therapy resistance, which suggests a pivotal role in therapy resistance and tumor relapse. Here we show that differentiated cells can re-acquire stemness through factors secreted from fibroblasts. This induced CSC state also coincides with re-acquisition of resistance to chemotherapy. Resistance induced in newly formed CSCs is mediated by the anti-apoptotic molecule BCLXL and inhibition of BCLXL with the BH3 mimetic ABT-737 sensitizes these cancer cells toward chemotherapy. These data point to an important interplay between tumor cells and their microenvironment in the regulation of stemness and therapy resistance. PMID:25483065

  3. Hematopoietic stem cells: an overview.

    PubMed

    Mosaad, Youssef Mohamed

    2014-12-01

    Considerable efforts have been made in recent years in understanding the mechanisms that govern hematopoietic stem cell (HSC) origin, development, differentiation, self-renewal, aging, trafficking, plasticity and transdifferentiation. Hematopoiesis occurs in sequential waves in distinct anatomical locations during development and these shifts in location are accompanied by changes in the functional status of the stem cells and reflect the changing needs of the developing organism. HSCs make a choice of either self-renewal or committing to differentiation. The balance between self-renewal and differentiation is considered to be critical to the maintenance of stem cell numbers. It is still under debate if HSC can rejuvenate infinitely or if they do not possess ''true" self-renewal and undergo replicative senescence such as any other somatic cell. Gene therapy applications that target HSCs offer a great potential for the treatment of hematologic and immunologic diseases. However, the clinical success has been limited by many factors. This review is intended to summarize the recent advances made in the human HSC field, and will review the hematopoietic stem cell from definition through development to clinical applications. PMID:25457002

  4. Metabolic Plasticity in Stem Cell Homeostasis and Differentiation

    PubMed Central

    Folmes, Clifford D.L.; Dzeja, Petras P.; Nelson, Timothy J.; Terzic, Andre

    2013-01-01

    Plasticity in energy metabolism allows stem cells to match the divergent demands of self-renewal and lineage specification. Beyond a role in energetic support, new evidence implicates nutrient-responsive metabolites as mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation of cell fate. Stem cell metabolism also offers a potential target for controlling tissue homeostasis and regeneration in aging and disease. In this Perspective, we cover recent progress establishing an emerging relationship between stem cell metabolism and cell fate control. PMID:23122287

  5. 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. PMID:24733351

  6. Mesenchymal Stem Cells as Therapeutics

    PubMed Central

    Parekkadan, Biju; Milwid, Jack M.

    2013-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID:20415588

  7. Stem Cells Deemed Safe for ALS Patients

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159627.html Stem Cells Deemed Safe for ALS Patients But further research ... June 29, 2016 (HealthDay News) -- Scientists report that stem cell therapy appears to be safe for people with ...

  8. International Society for Stem Cell Research

    MedlinePlus

    ... Industry Committee Session RUCDR Humanity in a Dish Stem Cell Engineering Junior Investigator Events Career Panel Meet the ... Scientific Program Confirmed Speakers Support/Exhibit Meeting Supporters Stem Cell Engineering 2014 Program Committee Featured Speakers Deepak Srivastava ...

  9. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  10. Stem Cells Deemed Safe for ALS Patients

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_159627.html Stem Cells Deemed Safe for ALS Patients But further ... June 29, 2016 (HealthDay News) -- Scientists report that stem cell therapy appears to be safe for people ...

  11. The Glycans of Stem Cells

    PubMed Central

    Lanctot, Pascal M.; Gage, Fred H.; Varki, Ajit P.

    2009-01-01

    Summary Glycans cover all cellular surfaces and, not surprisingly, are involved in many facets of stem cell biology and technology. For instance, coaxing stem cells to either proliferate or differentiate into the specific cell types needed for transplantation requires intricate glycan-dependent modulation of signalling molecules such as FGF-2, Wnt and Notch. Moreover, due to their prominent cell-surface localization and lineage-specific signatures, glycan epitopes such as the stage-specific embryonic antigens (Lewis X/SSEA-1, SSEA3–4) and tumor-rejection antigens (TRA1–60, 1–81) are ideally suited for identifying and isolating specific cell types from heterogeneous populations. Finally, the non-human sialic acid Neu5Gc has been detected on the surface of human embryonic stem cells due to metabolic incorporation from animal products used for their culture. Transplantation of Neu5Gc-contaminated cells poses immunological risks due to the presence, in humans, of circulating antibodies recognizing this glycan epitope. PMID:17681848

  12. Stem Cell Research Policies around the World

    PubMed Central

    Dhar, Deepali; Hsi-en Ho, John

    2009-01-01

    The proliferation of stem cell research, conflated with its ethical and moral implications, has led governments to attempt regulation of both the science and funding of stem cells. Due to a diversity of opinions and cultural viewpoints, no single policy or set of rules exist to govern stem cell research. Instead, each country has developed its own policy. The following map catalogs the general legal and political milleu regarding stem cell research by country. PMID:19774124

  13. Regulatory T Cells in Allogeneic Stem Cell Transplantation

    PubMed Central

    Nagler, Arnon

    2013-01-01

    Growing evidence suggests that cellular adoptive immunotherapy is becoming an attractive though challenging approach in regulating tumor immunity and alloresponses in clinical transplantation. Naturally arising CD4+CD25+Foxp3+ regulatory T cells (Treg) have emerged as a key component in this regard. Over the last decade, a large body of evidence from preclinical models has demonstrated their crucial role in auto- and tumor immunity and has opened the door to their “first-in-man” clinical application. Initial studies in clinical allogeneic stem cell transplantation are very encouraging and may pave the way for other applications. Further improvements in Treg ex vivo or in vivo expansion technologies will simplify their global clinical application. In this review, we discuss the current knowledge of Treg biology and their potential for cell-based immunotherapy in allogeneic stem cell transplantation. PMID:23737813

  14. Hepatic cancer stem cells may arise from adult ductal progenitors

    PubMed Central

    Nikolaou, Kostas C; Talianidis, Iannis

    2016-01-01

    Cancer stem cells (CSCs) are defined as cells within tumors that can self-renew and differentiate into heterogeneous lineages of cancerous cells. The origin of CSCs is not well understood. Recent evidence suggests that CSCs in hepatocellular carcinoma could be generated via oncogenic transformation and partial differentiation of adult hepatic ductal progenitor cells.

  15. Induced pluripotent stem cells generated without viral integration.

    PubMed

    Stadtfeld, Matthias; Nagaya, Masaki; Utikal, Jochen; Weir, Gordon; Hochedlinger, Konrad

    2008-11-01

    Pluripotent stem cells have been generated from mouse and human somatic cells by viral expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc. A major limitation of this technology is the use of potentially harmful genome-integrating viruses. We generated mouse induced pluripotent stem (iPS) cells from fibroblasts and liver cells by using nonintegrating adenoviruses transiently expressing Oct4, Sox2, Klf4, and c-Myc. These adenoviral iPS (adeno-iPS) cells show DNA demethylation characteristic of reprogrammed cells, express endogenous pluripotency genes, form teratomas, and contribute to multiple tissues, including the germ line, in chimeric mice. Our results provide strong evidence that insertional mutagenesis is not required for in vitro reprogramming. Adenoviral reprogramming may provide an improved method for generating and studying patient-specific stem cells and for comparing embryonic stem cells and iPS cells. PMID:18818365

  16. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    PubMed Central

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

  17. 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…

  18. Programming embryonic stem cells to neuronal subtypes

    PubMed Central

    Peljto, Mirza; Wichterle, Hynek

    2010-01-01

    Richness of neural circuits and specificity of neuronal connectivity depends on the diversification of nerve cells into functionally and molecularly distinct subtypes. While efficient methods for directed differentiation of embryonic stem cells (ESCs) into multiple principal neuronal classes have been established, only a few studies systematically examined the subtype diversity of in vitro derived nerve cells. Here we review evidence based on molecular and in vivo transplantation studies that ESC-derived spinal motor neurons and cortical layer V pyramidal neurons acquire subtype specific functional properties. We discuss similarities and differences in the role of cell intrinsic transcriptional programs, extrinsic signals and cell-cell interactions during subtype diversification of the two classes of nerve cells. We conclude that the high degree of fidelity with which differentiating ESCs recapitulate normal embryonic development provides a unique opportunity to explore developmental processes underlying specification of mammalian neuronal diversity in a simplified and experimentally accessible system. PMID:20970319

  19. 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…

  20. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... Health Professionals Questions to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment ... are the donor’s stem cells matched to the patient’s stem cells in allogeneic ...

  1. Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism

    PubMed Central

    YI, BO-RIM; CHOI, KELVIN J.; KIM, SEUNG U.; CHOI, KYUNG-CHUL

    2012-01-01

    Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include BRCA1, BRCA2, p53, PTEN, CHEK2 and ATM. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities. PMID:22736197

  2. 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

  3. Epigenetic Regulation of Hematopoietic Stem Cells

    PubMed Central

    Sharma, Shilpa; Gurudutta, Gangenahalli

    2016-01-01

    Hematopoietic stem cells are endowed with a distinct potential to bolster self-renewal and to generate progeny that differentiate into mature cells of myeloid and lymphoid lineages. Both hematopoietic stem cells and mature cells have the same genome, but their gene expression is controlled by an additional layer of epigenetics such as DNA methylation and post-translational histone modifications, enabling each cell-type to acquire various forms and functions. Until recently, several studies have largely focussed on the transcription factors andniche factors for the understanding of the molecular mechanisms by which hematopoietic cells replicate and differentiate. Several lines of emerging evidence suggest that epigenetic modifications eventually result in a defined chromatin structure and an “individual” gene expression pattern, which play an essential role in the regulation of hematopoietic stem cell self-renewal and differentiation. Distinct epigenetic marks decide which sets of genes may be expressed and which genes are kept silent. Epigenetic mechanisms are interdependent and ensure lifelong production of blood and bone marrow, thereby contributing to stem cell homeostasis. The epigenetic analysis of hematopoiesis raises the exciting possibility that chromatin structure is dynamic enough for regulated expression of genes. Though controlled chromatin accessibility plays an essential role in maintaining blood homeostasis; mutations in chromatin impacts on the regulation of genes critical to the development of leukemia. In this review, we explored the contribution of epigenetic machinery which has implications for the ramification of molecular details of hematopoietic self-renewal for normal development and underlying events that potentially co-operate to induce leukemia. PMID:27426084

  4. Methods for Stem Cell Production and Therapy

    NASA Technical Reports Server (NTRS)

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

  5. 28. Embryonic and adult stem cell therapy.

    PubMed

    Henningson, Carl T; Stanislaus, Marisha A; Gewirtz, Alan M

    2003-02-01

    Stem cells are characterized by the ability to remain undifferentiated and to self-renew. Embryonic stem cells derived from blastocysts are pluripotent (able to differentiate into many cell types). Adult stem cells, which were traditionally thought to be monopotent multipotent, or tissue restricted, have recently also been shown to have pluripotent properties. Adult bone marrow stem cells have been shown to be capable of differentiating into skeletal muscle, brain microglia and astroglia, and hepatocytes. Stem cell lines derived from both embryonic stem and embryonic germ cells (from the embryonic gonadal ridge) are pluripotent and capable of self-renewal for long periods. Therefore embryonic stem and germ cells have been widely investigated for their potential to cure diseases by repairing or replacing damaged cells and tissues. Studies in animal models have shown that transplantation of fetal, embryonic stem, or embryonic germ cells may be able to treat some chronic diseases. In this review, we highlight recent developments in the use of stem cells as therapeutic agents for three such diseases: Diabetes, Parkinson disease, and congestive heart failure. We also discuss the potential use of stem cells as gene therapy delivery cells and the scientific and ethical issues that arise with the use of human stem cells. PMID:12592319

  6. Evolutionary origins of germline segregation in Metazoa: evidence for a germ stem cell lineage in the coral Orbicella faveolata (Cnidaria, Anthozoa).

    PubMed

    Barfield, Sarah; Aglyamova, Galina V; Matz, Mikhail V

    2016-01-13

    The ability to segregate a committed germ stem cell (GSC) lineage distinct from somatic cell lineages is a characteristic of bilaterian Metazoans. However, the occurrence of GSC lineage specification in basally branching Metazoan phyla, such as Cnidaria, is uncertain. Without an independently segregated GSC lineage, germ cells and their precursors must be specified throughout adulthood from continuously dividing somatic stem cells, generating the risk of propagating somatic mutations within the individual and its gametes. To address the potential for existence of a GSC lineage in Anthozoa, the sister-group to all remaining Cnidaria, we identified moderate- to high-frequency somatic mutations and their potential for gametic transfer in the long-lived coral Orbicella faveolata (Anthozoa, Cnidaria) using a 2b-RAD sequencing approach. Our results demonstrate that somatic mutations can drift to high frequencies (up to 50%) and can also generate substantial intracolonial genetic diversity. However, these somatic mutations are not transferable to gametes, signifying the potential for an independently segregated GSC lineage in O. faveolata. In conjunction with previous research on germ cell development in other basally branching Metazoan species, our results suggest that the GSC system may be a Eumetazoan characteristic that evolved in association with the emergence of greater complexity in animal body plan organization and greater specificity of stem cell functions. PMID:26763699

  7. Muscle stem cells at a glance.

    PubMed

    Wang, Yu Xin; Dumont, Nicolas A; Rudnicki, Michael A

    2014-11-01

    Muscle stem cells facilitate the long-term regenerative capacity of skeletal muscle. This self-renewing population of satellite cells has only recently been defined through genetic and transplantation experiments. Although muscle stem cells remain in a dormant quiescent state in uninjured muscle, they are poised to activate and produce committed progeny. Unlike committed myogenic progenitor cells, the self-renewal capacity gives muscle stem cells the ability to engraft as satellite cells and capitulate long-term regeneration. Similar to other adult stem cells, understanding the molecular regulation of muscle stem cells has significant implications towards the development of pharmacological or cell-based therapies for muscle disorders. This Cell Science at a Glance article and accompanying poster will review satellite cell characteristics and therapeutic potential, and provide an overview of the muscle stem cell hallmarks: quiescence, self-renewal and commitment. PMID:25300792

  8. Novel Pathway of Adipogenesis through Cross-Talk between Adipose Tissue Macrophages, Adipose Stem Cells and Adipocytes: Evidence of Cell Plasticity

    PubMed Central

    Chazenbalk, Gregorio; Bertolotto, Cristina; Heneidi, Saleh; Jumabay, Medet; Trivax, Bradley; Aronowitz, Joel; Yoshimura, Kotaro; Simmons, Charles F.; Dumesic, Daniel A.; Azziz, Ricardo

    2011-01-01

    Introduction Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes. Research Design and Methods Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes), CD14 and CD68 (ATMs), CD34 (ASCs), and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPα and PPARγ. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+) ATMs. Results Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPα and PPARγ gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+)/CD68(+)/DLK (+) cell spheres supported the interaction of ATMs, ASCs and preadipocytes. Conclusions Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+)/CD68(+)/DLK(+) cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and

  9. The gene for erythropoietin receptor is expressed in multipotential hematopoietic and embryonal stem cells: evidence for differentiation stage-specific regulation.

    PubMed Central

    Heberlein, C; Fischer, K D; Stoffel, M; Nowock, J; Ford, A; Tessmer, U; Stocking, C

    1992-01-01

    The principal regulator of erythropoiesis is the glycoprotein erythropoietin, which interacts with a specific cell surface receptor (EpoR). A study aimed at analyzing EpoR gene regulation has shown that both pluripotent embryonal stem cells and early multipotent hematopoietic cells express EpoR transcripts. Commitment to nonerythroid lineages (e.g., macrophage or lymphocytic) results in the shutdown of EpoR gene expression, whereas commitment to the erythroid lineage is concurrent with or followed by dramatic increases in EpoR transcription. To determine whether gene activity could be correlated with chromatin alterations, DNase-hypersensitive sites (HSS) were mapped. Two major HSS located in the promoter region and within the first intron of the EpoR gene are present in all embryonal stem and hematopoietic cells tested, the intensities of which correlate well with EpoR expression levels. In addition, a third major HSS also located within the first intron of the EpoR gene is uniquely present in erythroid cells that express high levels of EpoR. Transfection assays show that sequences surrounding this major HSS impart erythroid cell-specific enhancer activity to a heterologous promoter and that this activity is at least in part mediated by GATA-1. These data, together with concordant expression levels of GATA-1 and EpoR in both early multipotent hematopoietic and committed erythroid cells, support a regulatory role of the erythroid cell-specific transcription factor GATA-1 in EpoR transcription in these cells. However, the lack of significant levels of GATA-1 expression in embryonal stem cells implies an alternative regulatory mechanism of EpoR transcription in cells not committed to the hematopoietic lineage. Images PMID:1312671

  10. Lung Cancer Stem Cell Lose Their Stemness Default State after Exposure to Microgravity

    PubMed Central

    Pisanu, Maria Elena; Noto, Alessia; De Vitis, Claudia; Masiello, Maria Grazia; Coluccia, Pierpaolo; Proietti, Sara; Giovagnoli, Maria Rosaria; Ricci, Alberto; Giarnieri, Enrico; Cucina, Alessandra; Ciliberto, Gennaro; Bizzarri, Mariano; Mancini, Rita

    2014-01-01

    Microgravity influences cell differentiation by modifying the morphogenetic field in which stem cells are embedded. Preliminary data showed indeed that stem cells are committed to selective differentiation when exposed to real or simulated microgravity. Our study provides evidence that a similar event occurs when cancer stem cells (CSCs) are cultured in microgravity. In the same time, a significant increase in apoptosis was recorded: those data point out that microgravity rescues CSCs from their relative quiescent state, inducing CSCs to lose their stemness features, as documented by the decrease in ALDH and the downregulation of both Nanog and Oct-4 genes. Those traits were stably acquired and preserved by CSCs when cells were placed again on a 1 g field. Studies conducted in microgravity on CSCs may improve our understanding of the fundamental role exerted by biophysical forces in cancer cell growth and function. PMID:25276790

  11. Imprinted Zac1 in neural stem cells

    PubMed Central

    Daniel, Guillaume; Schmidt-Edelkraut, Udo; Spengler, Dietmar; Hoffmann, Anke

    2015-01-01

    Neural stem cells (NSCs) and imprinted genes play an important role in brain development. On historical grounds, these two determinants have been largely studied independently of each other. Recent evidence suggests, however, that NSCs can reset select genomic imprints to prevent precocious depletion of the stem cell reservoir. Moreover, imprinted genes like the transcriptional regulator Zac1 can fine tune neuronal vs astroglial differentiation of NSCs. Zac1 binds in a sequence-specific manner to pro-neuronal and imprinted genes to confer transcriptional regulation and furthermore coregulates members of the p53-family in NSCs. At the genome scale, Zac1 is a central hub of an imprinted gene network comprising genes with an important role for NSC quiescence, proliferation and differentiation. Overall, transcriptional, epigenomic, and genomic mechanisms seem to coordinate the functional relationships of NSCs and imprinted genes from development to maturation, and possibly aging. PMID:25815116

  12. Arrhythmia in Stem Cell Transplantation

    PubMed Central

    Almeida, Shone O.; Skelton, Rhys J.; Adigopula, Sasikanth; Ardehali, Reza

    2015-01-01

    Synopsis Stem cell regenerative therapies hold promise for treating diseases across the spectrum of medicine. Recent clinical trials have confirmed the safety of stem cell delivery to the heart with promising but variable results. While significant progress has been made in the preclinical stages, the clinical application of cardiac cell therapy is limited by technical challenges, including inability to isolate a pure population of cardiac-specific progenitors capable of robust engraftment and regeneration, lack of appropriate pre-clinical animal models, uncertainty about the best mode of delivery, paucity of adequate imaging modalities, and lack of knowledge about the fate of transplanted cells. The inability of transplanted cells to structurally and functionally integrate into the host myocardium may pose arrhythmogenic risk to patients. This is in part dependent on the type of cell transplanted, where the expression of gap junctions such as connexin-43 is essential not only for electromechanical integration, but has also been found to be protective against electrical instability post-transplant. Additionally, certain methods of cell delivery, such as intramyocardial injection, carry a higher rate of arrhythmias. Other potential contributors to the arrhythmogenicity of cell transplantation include re-entrant pathways due to heterogeneity in conduction velocities between graft and host as well as graft automaticity. In this paper, we discuss the arrhythmogenic potential of cell delivery to the heart. PMID:26002399

  13. Microengineered synthetic cellular microenvironment for stem cells

    PubMed Central

    Sun, Yubing; Weng, Shinuo

    2014-01-01

    Stem cells possess the ability of self-renewal and differentiation into specific cell types. Therefore, stem cells have great potentials in fundamental biology studies and clinical applications. The most urgent desire for stem cell research is to generate appropriate artificial stem cell culture system, which can mimic the dynamic complexity and precise regulation of the in vivo biochemical and biomechanical signals, to regulate and direct stem cell behaviors. Precise control and regulation of the biochemical and biomechanical stimuli to stem cells have been successfully achieved using emerging micro/nanoengineering techniques. This review provides insights into how these micro/nanoengineering approaches, particularly microcontact printing and elastomeric micropost array, are applied to create dynamic and complex environment for stem cells culture. PMID:22639443

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

    PubMed Central

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

    2014-01-01

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

  15. 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

  16. Stem Cells in Teeth and Craniofacial Bones.

    PubMed

    Zhao, H; Chai, Y

    2015-11-01

    Stem cells are remarkable, and stem cell-based tissue engineering is an emerging field of biomedical science aiming to restore damaged tissue or organs. In dentistry and reconstructive facial surgery, it is of great interest to restore lost teeth or craniofacial bone defects using stem cell-mediated therapy. In the craniofacial region, various stem cell populations have been identified with regeneration potential. In this review, we provide an overview of the current knowledge concerning the various types of tooth- and craniofacial bone-related stem cells and discuss their in vivo identities and regulating mechanisms. PMID:26350960

  17. Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

    PubMed Central

    West, John D; Dorà, Natalie J; Collinson, J Martin

    2015-01-01

    In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed

  18. Klotho, stem cells, and aging

    PubMed Central

    Bian, Ao; Neyra, Javier A; Zhan, Ming; Hu, Ming Chang

    2015-01-01

    Aging is an inevitable and progressive biological process involving dysfunction and eventually destruction of every tissue and organ. This process is driven by a tightly regulated and complex interplay between genetic and acquired factors. Klotho is an antiaging gene encoding a single-pass transmembrane protein, klotho, which serves as an aging suppressor through a wide variety of mechanisms, such as antioxidation, antisenescence, antiautophagy, and modulation of many signaling pathways, including insulin-like growth factor and Wnt. Klotho deficiency activates Wnt expression and activity contributing to senescence and depletion of stem cells, which consequently triggers tissue atrophy and fibrosis. In contrast, the klotho protein was shown to suppress Wnt-signaling transduction, and inhibit cell senescence and preserve stem cells. A better understanding of the potential effects of klotho on stem cells could offer novel insights into the cellular and molecular mechanisms of klotho deficiency-related aging and disease. The klotho protein may be a promising therapeutic agent for aging and aging-related disorders. PMID:26346243

  19. Gametogenesis from Pluripotent Stem Cells.

    PubMed

    Saitou, Mitinori; Miyauchi, Hidetaka

    2016-06-01

    The germ cell lineage originates early in development and undergoes a series of complex developmental processes that culminate in the generation of fully matured gametes, the spermatozoa and the oocytes. Remarkably, researchers have been recapitulating these developmental pathways using mouse and human pluripotent stem cells (PSCs). With further studies, including those involving non-human primate models, human gametogenesis may be fully reconstituted from PSCs, which would profoundly facilitate our understanding of human germ cell development and infertility. Here we discuss groundbreaking studies that lay the foundation for this achievement, the current state of the field, and challenges for deriving gametes from hPSCs. PMID:27257761

  20. DNA repair in murine embryonic stem cells and differentiated cells

    SciTech Connect

    Tichy, Elisia D. Stambrook, Peter J.

    2008-06-10

    Embryonic stem (ES) cells are rapidly proliferating, self-renewing cells that have the capacity to differentiate into all three germ layers to form the embryo proper. Since these cells are critical for embryo formation, they must have robust prophylactic mechanisms to ensure that their genomic integrity is preserved. Indeed, several studies have suggested that ES cells are hypersensitive to DNA damaging agents and readily undergo apoptosis to eliminate damaged cells from the population. Other evidence suggests that DNA damage can cause premature differentiation in these cells. Several laboratories have also begun to investigate the role of DNA repair in the maintenance of ES cell genomic integrity. It does appear that ES cells differ in their capacity to repair damaged DNA compared to differentiated cells. This minireview focuses on repair mechanisms ES cells may use to help preserve genomic integrity and compares available data regarding these mechanisms with those utilized by differentiated cells.

  1. Tumourigenicity and Immunogenicity of Induced Neural Stem Cell Grafts Versus Induced Pluripotent Stem Cell Grafts in Syngeneic Mouse Brain.

    PubMed

    Gao, Mou; Yao, Hui; Dong, Qin; Zhang, Hongtian; Yang, Zhijun; Yang, Yang; Zhu, Jianwei; Xu, Minhui; Xu, Ruxiang

    2016-01-01

    Along with the development of stem cell-based therapies for central nervous system (CNS) disease, the safety of stem cell grafts in the CNS, such as induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs), should be of primary concern. To provide scientific basis for evaluating the safety of these stem cells, we determined their tumourigenicity and immunogenicity in syngeneic mouse brain. Both iPSCs and embryonic stem cells (ESCs) were able to form tumours in the mouse brain, leading to tissue destruction along with immune cell infiltration. In contrast, no evidence of tumour formation, brain injury or immune rejection was observed with iNSCs, neural stem cells (NSCs) or mesenchymal stem cells (MSCs). With the help of gene ontology (GO) enrichment analysis, we detected significantly elevated levels of chemokines in the brain tissue and serum of mice that developed tumours after ESC or iPSC transplantation. Moreover, we also investigated the interactions between chemokines and NF-κB signalling and found that NF-κB activation was positively correlated with the constantly rising levels of chemokines, and vice versa. In short, iNSC grafts, which lacked any resulting tumourigenicity or immunogenicity, are safer than iPSC grafts. PMID:27417157

  2. Tumourigenicity and Immunogenicity of Induced Neural Stem Cell Grafts Versus Induced Pluripotent Stem Cell Grafts in Syngeneic Mouse Brain

    PubMed Central

    Gao, Mou; Yao, Hui; Dong, Qin; Zhang, Hongtian; Yang, Zhijun; Yang, Yang; Zhu, Jianwei; Xu, Minhui; Xu, Ruxiang

    2016-01-01

    Along with the development of stem cell-based therapies for central nervous system (CNS) disease, the safety of stem cell grafts in the CNS, such as induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs), should be of primary concern. To provide scientific basis for evaluating the safety of these stem cells, we determined their tumourigenicity and immunogenicity in syngeneic mouse brain. Both iPSCs and embryonic stem cells (ESCs) were able to form tumours in the mouse brain, leading to tissue destruction along with immune cell infiltration. In contrast, no evidence of tumour formation, brain injury or immune rejection was observed with iNSCs, neural stem cells (NSCs) or mesenchymal stem cells (MSCs). With the help of gene ontology (GO) enrichment analysis, we detected significantly elevated levels of chemokines in the brain tissue and serum of mice that developed tumours after ESC or iPSC transplantation. Moreover, we also investigated the interactions between chemokines and NF-κB signalling and found that NF-κB activation was positively correlated with the constantly rising levels of chemokines, and vice versa. In short, iNSC grafts, which lacked any resulting tumourigenicity or immunogenicity, are safer than iPSC grafts. PMID:27417157

  3. 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. PMID:24778557

  4. 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

  5. Stem cells and repair of lung injuries

    PubMed Central

    Neuringer, Isabel P; Randell, Scott H

    2004-01-01

    Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung. PMID:15285789

  6. Visualizing the Functional Heterogeneity of Muscle Stem Cells.

    PubMed

    Kitajima, Yasuo; Ogawa, Shizuka; Ono, Yusuke

    2016-01-01

    Skeletal muscle stem cells are satellite cells that play crucial roles in tissue repair and regeneration after muscle injury. Accumulating evidence indicates that satellite cells are genetically and functionally heterogeneous, even within the same muscle. A small population of satellite cells possesses "stemness" and exhibits the remarkable ability to regenerate through robust self-renewal when transplanted into a regenerating muscle niche. In contrast, not all satellite cells self-renew. For example, some cells are committed myogenic progenitors that immediately undergo myogenic differentiation with minimal cell division after activation. Recent studies illuminate the cellular and molecular characteristics of the functional heterogeneity among satellite cells. To evaluate heterogeneity and stem cell dynamics, here we describe methods to conduct a clonal analysis of satellite cells and to visualize a slowly dividing cell population. PMID:27052612

  7. 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…

  8. Learning about Cancer by Studying Stem Cells

    MedlinePlus

    ... About Cancer by Studying Stem Cells Inside Life Science View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem ... Once Upon a Stem Cell This Inside Life Science article also appears on LiveScience . Learn about related ...

  9. Adult stem cells and tissue repair.

    PubMed

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells. PMID:12931235

  10. Transdifferentiation of differentiated stem cells contributes to remyelination.

    PubMed

    Chelluboina, Bharath; Dinh, Dzung H; Veeravalli, Krishna Kumar

    2015-01-01

    Evidence suggests that transdifferentiation of mesenchymal stem cells (MSCs) into various neuronal cells contributes to functional recovery after experimental spinal cord injury. Qiu et al. have recently published an exciting article in Stem Cell Research & Therapy demonstrating the transdifferentiation of already differentiated MSCs that contributes to remyelination of injured/regenerating axons, and thereby to functional recovery of spinal cord injured animals. The authors highlight the importance of interaction between neurotrophin-3 and tropomyosin receptor kinase C for the observed effects. This study provided important evidence that manipulation of rat bone marrow-derived MSCs before transplantation could enhance the therapeutic benefit of cell-based treatment. PMID:26437650

  11. Effects of nanotopography on stem cell phenotypes

    PubMed Central

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

    2009-01-01

    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. PMID:21607108

  12. The RNA-binding protein Musashi is required intrinsically to maintain stem cell identity.

    PubMed

    Siddall, Nicole A; McLaughlin, Eileen A; Marriner, Neisha L; Hime, Gary R

    2006-05-30

    A key goal of regenerative medicine is an understanding of the genetic factors that define the properties of stem cells. However, stem cell research in mammalian tissue has been hampered by a paucity of stem cell-specific markers. Although increasing evidence suggests that members of the Musashi (Msi) family of RNA-binding proteins play important functions in progenitor cells, it remains unclear whether there is a stem cell-autonomous requirement for Msi because of an inability to distinguish stem cells from early-lineage cells in mammalian tissues. Here, using the Drosophila testis as a model system for the study of stem cell regulation, we show specific evidence for a cell-autonomous requirement for Msi family proteins in regulating stem cell differentiation, leading to the identification of an RNA-binding protein required for spermatogonial stem cell maintenance. We found that loss of Msi function disrupts the balance between germ-line stem cell renewal and differentiation, resulting in the premature differentiation of germ-line stem cells. Moreover, we found that, although Msi is expressed in both somatic and germ cells, Msi function is required intrinsically in stem cells for maintenance of stem cell identity. We also discovered a requirement for Msi function in male meiosis, revealing that Msi has distinct roles at different stages of germ cell differentiation. We describe the complementary expression patterns of the murine Msi paralogues Msi1 and Msi2 during spermatogenesis, which support the idea of distinct, evolutionarily conserved roles of Msi. PMID:16717192

  13. Nutrient-sensing pathways and metabolic regulation in stem cells.

    PubMed

    Ochocki, Joshua D; Simon, M Celeste

    2013-10-14

    Stem cells exert precise regulation to maintain a balance of self-renewal and differentiation programs to sustain tissue homeostasis throughout the life of an organism. Recent evidence suggests that this regulation is modulated, in part, via metabolic changes and modifications of nutrient-sensing pathways such as mTOR and AMPK. It is becoming increasingly clear that stem cells inhibit oxidative phosphorylation in favor of aerobic glycolysis for energy production. Recent progress has detailed the molecular mechanisms of this metabolic phenotype and has offered insight into new metabolic pathways that may be involved in stem cell homeostasis. PMID:24127214

  14. Steroid hormones, steroid receptors, and breast cancer stem cells.

    PubMed

    Finlay-Schultz, Jessica; Sartorius, Carol A

    2015-06-01

    The ovarian hormones progesterone and estrogen play important roles in breast cancer etiology, proliferation, and treatment. Androgens may also contribute to breast cancer risk and progression. In recent years, significant advances have been made in defining the roles of these steroid hormones in stem cell homeostasis in the breast. Stem cells are potential origins of breast cancer and may dictate tumor phenotype. At least a portion of breast cancers are proposed to be driven by cancer stem cells (CSCs), cells that mimic the self-renewing and repopulating properties of normal stem cells, and can confer drug resistance. Progesterone has been identified as the critical hormone regulating normal murine mammary stem cell (MaSC) populations and normal human breast stem cells. Synthetic progestins increase human breast cancer risk; one theory speculates that this occurs through increased stem cells. Progesterone treatment also increases breast CSCs in established breast cancer cell lines. This is mediated in part through progesterone regulation of transcription factors, signal transduction pathways, and microRNAs. There is also emerging evidence that estrogens and androgens can regulate breast CSC numbers. The evolving concept that a breast CSC phenotype is dynamic and can be influenced by cell signaling and external cues emphasizes that steroid hormones could be crucial players in controlling CSC number and function. Here we review recent studies on steroid hormone regulation of breast CSCs, and discuss mechanisms by which this occurs. PMID:26265122

  15. Stem cell tracking with optically active nanoparticles

    PubMed Central

    Gao, Yu; Cui, Yan; Chan, Jerry KY; Xu, Chenjie

    2013-01-01

    Stem-cell-based therapies hold promise and potential to address many unmet clinical needs. Cell tracking with modern imaging modalities offers insight into the underlying biological process of the stem-cell-based therapies, with the goal to reveal cell survival, migration, homing, engraftment, differentiation, and functions. Adaptability, sensitivity, resolution, and non-invasiveness have contributed to the longstanding use of optical imaging for stem cell tracking and analysis. To identify transplanted stem cells from the host tissue, optically active probes are usually used to label stem cells before the administration. In comparison to the traditional fluorescent probes like fluorescent proteins and dyes, nanoparticle-based probes are advantageous in terms of the photo-stabilities and minimal changes to the cell phenotype. The main focus here is to overview the recent development of optically active nanoparticles for stem cells tracking. The related optical imaging modalities include fluorescence imaging, photoacoustic imaging, Raman and surface enhanced Raman spectroscopy imaging. PMID:23638335

  16. 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

  17. Stem cells - biological update and cell therapy progress.

    PubMed

    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

  18. Therapeutic Implications of Leukemic Stem Cell Pathways

    PubMed Central

    Chumsri, Saranya; Matsui, William; Burger, Angelika M.

    2008-01-01

    An emerging concept in cancer biology is that a rare population of cancer stem cells exists among the heterogeneous cell mass that constitutes a tumor. This concept is best understood in human myeloid leukemia. Normal and malignant hematopoietic stem cell functions are defined by a common set of critical stemness genes that regulate self-renewal and developmental pathways. Several stemness factors, such as Notch or telomerase, show differential activation in normal hematopoietic versus leukemia stem cells. These differences could be exploited therapeutically even with drugs that are already in clinical use for the treatment of leukemia. The translation of novel and existing leukemic stem cell – directed therapies into clinical practice, however, will require changes in clinical trial design and the inclusion of stem cell biomarkers as correlative end points. PMID:18006753

  19. Primary Bioassay of Human Myeloma Stem Cells

    PubMed Central

    Hamburger, Anne; Salmon, Sydney E.

    1977-01-01

    The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 105-106 and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B)-cell

  20. Non-Hematopoietic Stem Cells in Umbilical Cord Blood

    PubMed Central

    Matsumoto, Taro; Mugishima, Hideo

    2009-01-01

    Allogeneic umbilical cord blood (UCB) transplantation has been used to treat a variety of malignant and non-malignant diseases. Recent studies show convincing evidence that UCB contains not only hematopoietic progenitors, but also several types of stem and progenitor cells providing a high proliferative capacity and a variety of differentiation potentials. UCB-derived cells offer multiple advantages over adult stem cells from other sources like bone marrow (BM), because UCB can be collected without painful procedure, easily available in virtually unlimited supply, and has not been exposed to immunologic challenge. In addition, cord blood transplantation is now an established field with great potential and no serious ethical issue by establishment of public UCB banks throughout the world. Therefore UCB-derived non-hematopoietic stem cells may provide an attractive cell source for tissue repair and regeneration. It is generally accepted that UCB contains endothelial progenitor cells (EPC), mesenchymal stromal cells (MSC), unrestricted somatic stem cells (USSC), very small embryonic-like stem cells (VSEL), multilineage progenitor cells (MLPC), and neuronal progenitor cells. This review focuses on biological properties of these non-hematopoietic stem/progenitor cells derived from human UCB and their potential use in cell based therapies. PMID:24855525

  1. Hospital infection control in hematopoietic stem cell transplant recipients.

    PubMed Central

    Dykewicz, C. A.

    2001-01-01

    Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients contains a section on hospital infection control including evidence-based recommendations regarding ventilation, construction, equipment, plants, play areas and toys, health-care workers, visitors, patient skin and oral care, catheter-related infections, drug-resistant organisms, and specific nosocomial infections. These guidelines are intended to reduce the number and severity of hospital infections in hematopoietic stem cell transplant recipients. PMID:11294720

  2. Embryonic Stem Cells/Induced Pluripotent Stem Cells

    PubMed Central

    Feng, Xuezhu; Zhang, Jiuchun; Smuga-Otto, Kimberly; Tian, Shulan; Yu, Junying; Stewart, Ron; Thomson, James A.

    2012-01-01

    Unlike mouse embryonic stem cells (ESCs), which are closely related to the inner cell mass, human ESCs appear to be more closely related to the later primitive ectoderm. For example, human ESCs and primitive ectoderm share a common epithelial morphology, growth factor requirements, and the potential to differentiate to all three embryonic germ layers. However, it has previously been shown that human ESCs can also differentiate to cells expressing markers of trophoblast, an extraembryonic lineage formed before the formation of primitive ectoderm. Here, we show that phorbol ester 12-O-tetradecanoylphorbol 13-acetate causes human ESCs to undergo an epithelial mesenchymal transition and to differentiate into cells expressing markers of parietal endoderm, another extraembryonic lineage. We further confirmed that this differentiation is through the activation of protein kinase C (PKC) pathway and demonstrated that a particular PKC subtype, PKC-δ, is most responsible for this transition. PMID:22213079

  3. The therapeutic potential of stem cells

    PubMed Central

    Watt, Fiona M.; Driskell, Ryan R.

    2010-01-01

    In recent years, there has been an explosion of interest in stem cells, not just within the scientific and medical communities but also among politicians, religious groups and ethicists. Here, we summarize the different types of stem cells that have been described: their origins in embryonic and adult tissues and their differentiation potential in vivo and in culture. We review some current clinical applications of stem cells, highlighting the problems encountered when going from proof-of-principle in the laboratory to widespread clinical practice. While some of the key genetic and epigenetic factors that determine stem cell properties have been identified, there is still much to be learned about how these factors interact. There is a growing realization of the importance of environmental factors in regulating stem cell behaviour and this is being explored by imaging stem cells in vivo and recreating artificial niches in vitro. New therapies, based on stem cell transplantation or endogenous stem cells, are emerging areas, as is drug discovery based on patient-specific pluripotent cells and cancer stem cells. What makes stem cell research so exciting is its tremendous potential to benefit human health and the opportunities for interdisciplinary research that it presents. PMID:20008393

  4. Engineering Stem Cells for Biomedical Applications.

    PubMed

    Yin, Perry T; Han, Edward; Lee, Ki-Bum

    2016-01-01

    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

  5. Regulatory Insight into the European Human Pluripotent Stem Cell Registry

    PubMed Central

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

    2014-01-01

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

  6. Regulatory insight into the European human pluripotent stem cell registry.

    PubMed

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

    2014-12-01

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

  7. 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

  8. Reforming craniofacial orthodontics via stem cells

    PubMed Central

    Mohanty, Pritam; Prasad, N.K.K.; Sahoo, Nivedita; Kumar, Gunjan; Mohanty, Debapreeti; Sah, Sushila

    2015-01-01

    Stem cells are the most interesting cells in cell biology. They have the potential to evolve as one of the most powerful technologies in the future. The future refers to an age where it will be used extensively in various fields of medical and dental sciences. Researchers have discovered a number of sources from which stem cells can be derived. Craniofacial problems are very common and occur at all ages. Stem cells can be used therapeutically in almost every field of health science. In fact, many procedures will be reformed after stem cells come into play. This article is an insight into the review of the current researches being carried out on stem cells and its use in the field of orthodontics, which is a specialized branch of dentistry. Although the future is uncertain, there is a great possibility that stem cells will be used extensively in almost all major procedures of orthodontics. PMID:25767761

  9. Cellular mechanisms of somatic stem cell aging.

    PubMed

    Jung, Yunjoon; Brack, Andrew S

    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

  10. Combination stem cell therapy for heart failure

    PubMed Central

    2010-01-01

    Patients with congestive heart failure (CHF) that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a) increasing stem cell migration to the heart; b) augmenting stem cell activity; and c) combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells. PMID:20398245

  11. Cryopreservation of Hematopoietic Stem Cells

    PubMed Central

    Berz, David; McCormack, Elise M.; Winer, Eric S.; Colvin, Gerald A.; Quesenberry, Peter J.

    2007-01-01

    Stem cell transplantation represents a critical approach for the treatment of many malignant and non-malignant diseases. The foundation for these approaches is the ability to cryopreserve marrow cells for future use. This technique is routinely employed in all autologous settings and is critical for cord blood transplantation. A variety of cryopreservatives have been used with multiple freezing and thawing techniques as outlined in the later chapters. Freezing efficiency has been proven repeatedly and the ability of long-term stored marrow to repopulate has been established. Standard approaches outlined here are used in many labs as the field continues to evolve. PMID:17266054

  12. Adult Stem Cell Responses to Nanostimuli

    PubMed Central

    Tsimbouri, Penelope M.

    2015-01-01

    Adult or mesenchymal stem cells (MSCs) have been found in different tissues in the body, residing in stem cell microenvironments called “stem cell niches”. They play different roles but their main activity is to maintain tissue homeostasis and repair throughout the lifetime of an organism. Their ability to differentiate into different cell types makes them an ideal tool to study tissue development and to use them in cell-based therapies. This differentiation process is subject to both internal and external forces at the nanoscale level and this response of stem cells to nanostimuli is the focus of this review. PMID:26193326

  13. Stem Cell-Based Neuroprotective and Neurorestorative Strategies

    PubMed Central

    Hung, Chia-Wei; Liou, Ying-Jay; Lu, Shao-Wei; Tseng, Ling-Ming; Kao, Chung-Lan; Chen, Shih-Jen; Chiou, Shih-Hwa; Chang, Charn-Jung

    2010-01-01

    Stem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs) derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke and Parkinson’s disease. Moreover, the potential and possible utilities of induced pluripotent stem cells (iPS), reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases. PMID:20559500

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

    SciTech Connect

    Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva; Nemet, Katalin; Uher, Ferenc; Sarkadi, Balazs; Apati, Agota

    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 of 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.

  15. Natural Products That Target Cancer Stem Cells.

    PubMed

    Moselhy, Jim; Srinivasan, Sowmyalakshmi; Ankem, Murali K; Damodaran, Chendil

    2015-11-01

    The cancer stem cell model suggests that tumor initiation is governed by a small subset of distinct cells with stem-like character termed cancer stem cells (CSCs). CSCs possess properties of self-renewal and intrinsic survival mechanisms that contribute to resistance of tumors to most chemotherapeutic drugs. The failure to eradicate CSCs during the course of therapy is postulated to be the driving force for tumor recurrence and metastasis. Recent studies have focused on understanding the unique phenotypic properties of CSCs from various tumor types, as well as the signaling pathways that underlie self-renewal and drug resistance. Natural products (NPs) such as those derived from botanicals and food sources may modulate vital signaling pathways involved in the maintenance of CSC phenotype. The Wingless/Integrated (WNT), Hedgehog, Notch and PI3K/AKT/mTOR pathways have all been associated with quiescence and self-renewal of CSCs, as well as execution of CSC function including differentiation, multidrug resistance and metastasis. Recent studies evaluating NPs against CSC support the epidemiological evidence linking plant-based diets with reduced malignancy rates. This review covers the key aspects of NPs as modulators of CSC fate. PMID:26503998

  16. Lifting the Mist on Gastric Stem Cells.

    PubMed

    Varga, Julia; Greten, Florian R

    2016-01-01

    In a recent issue of Cancer Cell, Hayakawa et al. (2015) demonstrate that Mist1(+) gastric stem cells are supported by a specialized niche composed of Cxcl12(+) endothelium and Wnt5a-producing Cxcr4(+) innate lymphoid cells. In diffuse-type gastric cancer this perivascular stem cell niche is expanded and can be exploited for cancer therapy. PMID:26748749

  17. Imported Stem Cells Strike against Stroke.

    PubMed

    Péron, Sophie; Berninger, Benedikt

    2015-11-01

    Cells with neural stem cell (NSC)-like properties can be isolated from the cortex of adult brains following injury, but their origins and function are unclear. Now in Cell Stem Cell, Faiz et al. (2015) show that subventricular-zone-derived NSCs home to injured cortical area following stroke, where they generate reactive astrocytes. PMID:26544109

  18. Neuromuscular complications of hematopoietic stem cell transplantation.

    PubMed

    Ruzhansky, Katherine M; Brannagan, Thomas H

    2015-10-01

    Neuromuscular diseases such as polymyositis, dermatomyositis, peripheral neuropathy, and disorders of neuromuscular transmission are reported to be complications of hematopoietic stem cell transplantation (HSCT). Although cases have been reported with allogeneic HSCT in the setting of chronic graft versus host disease, they are also known to occur without evidence thereof and even occur in the setting of autologous HSCT. The 2005 National Institutes of Health Consensus Criteria classify polymyositis and dermatomyositis as "distinctive" features, and neuropathy and MG as "other" features. These neuromuscular complications present very similarly to the idiopathic autoimmune disorders and respond to similar treatment modalities. PMID:26044357

  19. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients. PMID:26483336

  20. Emerging targets for glioblastoma stem cell therapy

    PubMed Central

    Safa, Ahmad R.; Saadatzadeh, Mohammad Reza; Cohen-Gadol, Aaron A.; Pollok, Karen E.; Bijangi-Vishehsaraei, Khadijeh

    2016-01-01

    Abstract Glioblastoma multiforme (GBM), designated as World Health Organization (WHO) grade IV astrocytoma, is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations, including GBM stem cells (GSCs) which are believed to contribute to tumor recurrence following initial response to therapies. Emerging evidence demonstrates that GBM tumors are initiated from GSCs. The development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate stemness, proliferation and migration of GSCs, immunotherapy, and non-coding microRNAs may provide better means of treating GBM. Identification and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting GSCs. Several signaling pathways including mTOR, AKT, maternal embryonic leucine zipper kinase (MELK), NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain GSC properties. Moreover, the data published in the Cancer Genome Atlas (TCGA) specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM tumorigenesis. Studying such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation therapy. Furthemore, recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs, but the differentiated GBM cells and the entire bulk of tumor cells. PMID:26616589

  1. The stem cell secretome and its role in brain repair.

    PubMed

    Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

    2013-12-01

    Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. PMID:23827856

  2. The stem cell secretome and its role in brain repair

    PubMed Central

    Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

    2014-01-01

    Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. PMID:23827856

  3. Stem Cell Therapy for Autism

    PubMed Central

    Ichim, Thomas E; Solano, Fabio; Glenn, Eduardo; Morales, Frank; Smith, Leonard; Zabrecky, George; Riordan, Neil H

    2007-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions whose incidence is reaching epidemic proportions, afflicting approximately 1 in 166 children. Autistic disorder, or autism is the most common form of ASD. Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism. PMID:17597540

  4. Hymyc1 Downregulation Promotes Stem Cell Proliferation in Hydra vulgaris

    PubMed Central

    Ambrosone, Alfredo; Marchesano, Valentina; Tino, Angela; Hobmayer, Bert; Tortiglione, Claudia

    2012-01-01

    Hydra is a unique model for studying the mechanisms underlying stem cell biology. The activity of the three stem cell lineages structuring its body constantly replenishes mature cells lost due to normal tissue turnover. By a poorly understood mechanism, stem cells are maintained through self-renewal while concomitantly producing differentiated progeny. In vertebrates, one of many genes that participate in regulating stem cell homeostasis is the protooncogene c-myc, which has been recently identified also in Hydra, and found expressed in the interstitial stem cell lineage. In the present paper, by developing a novel strategy of RNA interference-mediated gene silencing (RNAi) based on an enhanced uptake of small interfering RNAi (siRNA), we provide molecular and biological evidence for an unexpected function of the Hydra myc gene (Hymyc1) in the homeostasis of the interstitial stem cell lineage. We found that Hymyc1 inhibition impairs the balance between stem cell self renewal/differentiation, as shown by the accumulation of stem cell intermediate and terminal differentiation products in genetically interfered animals. The identical phenotype induced by the 10058-F4 inhibitor, a disruptor of c-Myc/Max dimerization, demonstrates the specificity of the RNAi approach. We show the kinetic and the reversible feature of Hymyc1 RNAi, together with the effects displayed on regenerating animals. Our results show the involvement of Hymyc1 in the control of interstitial stem cell dynamics, provide new clues to decipher the molecular control of the cell and tissue plasticity in Hydra, and also provide further insights into the complex myc network in higher organisms. The ability of Hydra cells to uptake double stranded RNA and to trigger a RNAi response lays the foundations of a comprehensive analysis of the RNAi response in Hydra allowing us to track back in the evolution and the origin of this process. PMID:22292012

  5. Mesenchymal Stem Cells in Cardiology.

    PubMed

    White, Ian A; Sanina, Cristina; Balkan, Wayne; Hare, Joshua M

    2016-01-01

    Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one-third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy. MSCs are potent mediators of cardiac repair and are therefore an attractive tool in the development of preclinical and clinical trials. MSCs are capable of secreting a large array of soluble factors, which have had demonstrated effects on pathogenic cardiac remolding, fibrosis, immune activation, and cardiac stem cell proliferation within the damaged heart. MSCs are also capable of differentiation into cardiomyocytes, endothelial cells, and vascular smooth muscle cells, although the relative contribution of trilineage differentiation and paracrine effectors on cardiac repair remains the subject of active investigation. PMID:27236666

  6. Modeling head and neck cancer stem cell-mediated tumorigenesis.

    PubMed

    Pearson, Alexander T; Jackson, Trachette L; Nör, Jacques E

    2016-09-01

    A large body of literature has emerged supporting the importance of cancer stem cells (CSCs) in the pathogenesis of head and neck cancers. CSCs are a subpopulation of cells within a tumor that share the properties of self-renewal and multipotency with stem cells from normal tissue. Their functional relevance to the pathobiology of cancer arises from the unique properties of tumorigenicity, chemotherapy resistance, and their ability to metastasize and invade distant tissues. Several molecular profiles have been used to discriminate a stem cell from a non-stem cell. CSCs can be grown for study and further enriched using a number of in vitro techniques. An evolving option for translational research is the use of mathematical and computational models to describe the role of CSCs in complex tumor environments. This review is focused discussing the evidence emerging from modeling approaches that have clarified the impact of CSCs to the biology of cancer. PMID:27151511

  7. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases

    PubMed Central

    Suksuphew, Sarawut; Noisa, Parinya

    2015-01-01

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients. PMID:25815135

  8. Control of stem cell fate by engineering their micro and nanoenvironment

    PubMed Central

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

    2015-01-01

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

  9. Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

    PubMed Central

    Choi, Moonhwan; Ban, Taehyun; Rhim, Taiyoun

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs. PMID:24598998

  10. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  11. Stem cells in the light of evolution

    PubMed Central

    Chakraborty, Chiranjib; Agoramoorthy, Govindasamy

    2012-01-01

    All organisms depend on stem cells for their survival. As a result, stem cells may be a prerequisite for the evolution of specific characteristics in organisms that include regeneration, multicellularity and coloniality. Stem cells have attracted the attention of biologists and medical scientists for a long time. These provide materials for regenerative medicine. We review in this paper, the link between modern stem cell research and early studies in ancient organisms. It also outlines details on stem cells in the light of evolution with an emphasis on their regeneration potential, coloniality and multicellularity. The information provided might be of use to molecular biologists, medical scientists and developmental biologists who are engaged in integrated research involving the stem cells. PMID:22825600

  12. Two-photon imaging of stem cells

    NASA Astrophysics Data System (ADS)

    Uchugonova, A.; Gorjup, E.; Riemann, I.; Sauer, D.; König, K.

    2008-02-01

    A variety of human and animal stem cells (rat and human adult pancreatic stem cells, salivary gland stem cells, dental pulpa stem cells) have been investigated by femtosecond laser 5D two-photon microscopy. Autofluorescence and second harmonic generation have been imaged with submicron spatial resolution, 270 ps temporal resolution, and 10 nm spectral resolution. In particular, NADH and flavoprotein fluorescence was detected in stem cells. Major emission peaks at 460nm and 530nm with typical mean fluorescence lifetimes of 1.8 ns and 2.0 ns, respectively, were measured using time-correlated single photon counting and spectral imaging. Differentiated stem cells produced the extracellular matrix protein collagen which was detected by SHG signals at 435 nm.

  13. Applications of Microfluidics in Stem Cell Biology.

    PubMed

    Zhang, Qiucen; Austin, Robert H

    2012-12-01

    Stem cell research can significantly benefit from recent advances of microfluidics technology. In a rationally designed microfluidics device, analyses of stem cells can be done in a much deeper and wider way than in a conventional tissue culture dish. Miniaturization makes analyses operated in a high-throughput fashion, while controls of fluids help to reconstruct the physiological environments. Through integration with present characterization tools like fluorescent microscope, microfluidics offers a systematic way to study the decision-making process of stem cells, which has attractive medical applications. In this paper, recent progress of microfluidics devices on stem cell research are discussed. The purpose of this review is to highlight some key features of microfluidics for stem cell biologists, as well as provide physicists/engineers an overview of how microfluidics has been and could be used for stem cell research. PMID:23336098

  14. Cancer stem cells: a metastasizing menace!

    PubMed

    Bandhavkar, Saurabh

    2016-04-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. PMID:26773710

  15. Mesenchymal stem cell characteristics of dental pulp and periodontal ligament stem cells after in vivo transplantation.

    PubMed

    Lei, Ming; Li, Kun; Li, Bei; Gao, Li-Na; Chen, Fa-Ming; Jin, Yan

    2014-08-01

    Mesenchymal stem cells (MSCs) isolated from human postnatal dental pulp and periodontal ligament (PDL) tissues can give rise to multilineage differentiation in vitro and generate related dental tissues in vivo. However, the cell properties of human dental pulp stem cells (DPSCs) and PDL stem cells (PDLSCs) after in vivo implantation remain largely unidentified. In this study, cells were re-isolated from in vivo-generated dental pulp-like and PDL-like tissues (termed re-DPCs and re-PDLCs, respectively) as a result of ectopic transplantation of human DPSC and PDLSC sheets. The cell characteristics in terms of colony-forming ability, cell surface antigens and multi-differentiation potentials were all evaluated before and after implantation. It was found that re-DPCs and re-PDLCs were of human and mesenchymal origin and positive for MSC markers such as STRO-1, CD146, CD29, CD90 and CD105; and, to some extent, re-DPCs could maintain their colony forming abilities. Moreover, both cell types were able to form mineral deposits and differentiate into adipocytes and chondrocytes; however, quantitative analysis and related gene expression determination showed that the osteo-/chondro-differentiation capabilities of re-DPCs and re-PDLCs were significantly reduced compared to those of DPSCs and PDLSCs, respectively (P < 0.05); re-PDLCs showed a greater reduction potential than re-DPCs. We conclude that DPSCs and PDLSCs may maintain their MSC characteristics after in vivo implantation and, compared to PDLSCs, DPSCs appear much more stable under in vivo conditions. These findings provide additional cellular and molecular evidence that supports expanding the use of dental tissue-derived stem cells in cell therapy and tissue engineering. PMID:24824581

  16. Stem cells from amniotic fluid - Potential for regenerative medicine.

    PubMed

    Loukogeorgakis, Stavros P; De Coppi, Paolo

    2016-02-01

    Regenerative medicine has recently been established as an emerging field focussing on repair, replacement or regeneration of cells, tissues and whole organs. The significant recent advances in the field have intensified the search for novel sources of stem cells with potential for therapy. Recently, researchers have identified the amniotic fluid as an untapped source of stem cells that are multipotent, possess immunomodulatory properties and do not have the ethical and legal limitations of embryonic stem cells. Stem cells from the amniotic fluid have been shown to differentiate into cell lineages representing all three embryonic germ layers without generating tumours, which make them an ideal candidate for tissue engineering applications. In addition, their ability to engraft in injured organs and modulate immune and repair responses of host tissues suggest that transplantation of such cells may be useful for the treatment of various degenerative and inflammatory diseases affecting major tissues/organs. This review summarises the evidence on amniotic fluid cells over the past 15 years and explores the potential therapeutic applications of amniotic fluid stem cells and amniotic fluid mesenchymal stem cells. PMID:26542929

  17. Therapeutic journeys: the hopeful travails of stem cell tourists.

    PubMed

    Petersen, Alan; Seear, Kate; Munsie, Megan

    2014-06-01

    The recent growth of so-called stem cell tourism reflects the high optimism that currently surrounds stem cell science. Stem cell treatments for various conditions are increasingly advertised over the Internet as being available at hospitals and clinics around the world. However, most are clinically unproven. Despite numerous warnings from scientists about the dangers posed by such treatments, many individuals are evidently prepared to take the risk, sometimes on more than one occasion. This article explores the dynamics of hope that underpin stem cell tourism. Drawing on ideas from the sociology of hope, as applied to biomedicine, the article explores how hope is constructed and shapes actions in relation to stem cell treatments. Making reference to the findings from an Australian study of patients and carers who travelled overseas to receive stem cell treatments, it is argued that hope has an ambiguous significance in the context of deregulated health care. As we explain, this has implications for patients' and carers' treatment decisions and experiences. The findings are discussed in light of current responses to stem cell tourism. PMID:24266861

  18. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.

    PubMed

    Fiorenzano, Alessandro; Pascale, Emilia; D'Aniello, Cristina; Acampora, Dario; Bassalert, Cecilia; Russo, Francesco; Andolfi, Gennaro; Biffoni, Mauro; Francescangeli, Federica; Zeuner, Ann; Angelini, Claudia; Chazaud, Claire; Patriarca, Eduardo J; Fico, Annalisa; Minchiotti, Gabriella

    2016-01-01

    Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo. PMID:27586544

  19. Stem Cells and Lung Regeneration

    PubMed Central

    El-Badrawy, Mohammad K.; Shalabi, Nesrein M.; Mohamed, Mie A.; Ragab, Amany; Abdelwahab, Heba Wagih

    2016-01-01

    Background:Tissues such as the lung, liver, and pancreas that have a low steady-state cell turnover yet can respond robustly after injury to replace damaged cells. The airway epithelium is exposed to inhaled particles and pathogens that may lead to the development of a many infectious and inflammatory respiratory diseases. Lung transplantation is an accepted modality of treatment for end-stage lung diseases. Since the early 1990 s, more than 26,000 lung transplants have been performed at centers worldwide. However, the availability of donor tissues and organs is limited, which presents a serious limitation for widespread transplantation surgery. The appearance of bioengineered lung and tracheal tissue transplants is considered a promising alternative to the classical transplantation of donor organ/tissue. Stem cells therapy arises as a new therapeutic approach, with a wide application potential. PMID:27426083

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

    SciTech Connect

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    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 of 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.

  1. Stem cell reprogramming: A 3D boost

    NASA Astrophysics Data System (ADS)

    Abilez, Oscar J.; Wu, Joseph C.

    2016-03-01

    Biophysical factors in an optimized three-dimensional microenvironment enhance the reprogramming efficiency of human somatic cells into pluripotent stem cells when compared to traditional cell-culture substrates.

  2. Burning Fat Fuels Leukemic Stem Cell Heterogeneity.

    PubMed

    Thomas, Daniel; Majeti, Ravindra

    2016-07-01

    Obese leukemia patients exhibit reduced survival after chemotherapy, suggesting an important role of adipose tissue in disease progression. In this issue of Cell Stem Cell, Ye et al. (2016) reveal metabolic heterogeneity in leukemic stem cell (LSC) subpopulations and show that chemotherapy-resistant CD36+ LSCs co-opt gonadal adipose tissue to support their metabolism and survival. PMID:27392217

  3. Germline Stem Cell Transplantation and Transgenesis

    PubMed Central

    Brinster, Ralph L.

    2016-01-01

    The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals. PMID:12077400

  4. Energy Metabolism Plays a Critical Role in Stem Cell Maintenance and Differentiation.

    PubMed

    Hu, Chenxia; Fan, Linxiao; Cen, Panpan; Chen, Ermei; Jiang, Zhengyi; Li, Lanjuan

    2016-01-01

    Various stem cells gradually turned to be critical players in tissue engineering and regenerative medicine therapies. Current evidence has demonstrated that in addition to growth factors and the extracellular matrix, multiple metabolic pathways definitively provide important signals for stem cell self-renewal and differentiation. In this review, we mainly focus on a detailed overview of stem cell metabolism in vitro. In stem cell metabolic biology, the dynamic balance of each type of stem cell can vary according to the properties of each cell type, and they share some common points. Clearly defining the metabolic flux alterations in stem cells may help to shed light on stemness features and differentiation pathways that control the fate of stem cells. PMID:26901195

  5. Energy Metabolism Plays a Critical Role in Stem Cell Maintenance and Differentiation

    PubMed Central

    Hu, Chenxia; Fan, Linxiao; Cen, Panpan; Chen, Ermei; Jiang, Zhengyi; Li, Lanjuan

    2016-01-01

    Various stem cells gradually turned to be critical players in tissue engineering and regenerative medicine therapies. Current evidence has demonstrated that in addition to growth factors and the extracellular matrix, multiple metabolic pathways definitively provide important signals for stem cell self-renewal and differentiation. In this review, we mainly focus on a detailed overview of stem cell metabolism in vitro. In stem cell metabolic biology, the dynamic balance of each type of stem cell can vary according to the properties of each cell type, and they share some common points. Clearly defining the metabolic flux alterations in stem cells may help to shed light on stemness features and differentiation pathways that control the fate of stem cells. PMID:26901195

  6. Preconditioning Stem Cells for In Vivo Delivery

    PubMed Central

    Sart, Sébastien; Ma, Teng

    2014-01-01

    Abstract Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation. PMID:25126478

  7. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  8. Breaking ground on translational stem cell research.

    PubMed

    Hall, Zach W; Kahler, David; Manganiello, Michael; Egli, Dieter; James, Daylon; Marolt, Darja; Marlot, Darja; Fasano, Christopher; Ichida, Justin; Noggle, Scott; Solomon, Susan L; McKeon, David; Smith, Kristin; Marshall, Caroline

    2010-03-01

    Sponsored by the New York Stem Cell Foundation (NYSCF), the "Fourth Annual Translational Stem Cell Research Conference: Breaking Ground" convened October 13-14, 2009 at The Rockefeller University in New York City to discuss translational stem cell research. Attracting over 400 scientists, patient advocates, and stem cell research supporters from fifteen countries, the two-day conference featured an afternoon of panel discussions, intended for a broad audience, followed by a second day of scientific talks and poster presentations. This report summarizes both days of this exciting conference. PMID:20233361

  9. The Patentability of Stem Cells in Australia.

    PubMed

    Petering, Jenny; Cowin, Prue

    2015-10-01

    The potential therapeutic applications of stem cells are unlimited. However, the ongoing political and social debate surrounding the intellectual property and patenting considerations of stem cell research has led to the implementation of strict legislative regulations. In Australia the patent landscape surrounding stem cells has evolved considerably over the past 20 years. The Australian Patents Act 1990 includes a specific exclusion to the patentability of human beings and of biological processes for their generation. However, this exclusion has received no judicial consideration to date, and so its scope and potential impact on stem cell patents is unclear. PMID:26134481

  10. [Stem cells - biology and therapeutic application].

    PubMed

    Sikora, Magdalena A; Olszewski, Waldemar L

    2004-04-01

    Enormous hope is connected with stem cells with regard to cell therapy, and this has become one of the most dynamically developing areas of science at the moment. A stem cell has unlimited potential for self-renewal. It appears that it can be a source of in vitro differentiated progeny cells capable of repairing damaged tissue. These review provides information about the biological properties of embryonic stem cells, i.e. ESs (embryonic stem cells), EGs (embryonic germ cells), and ECs (embryonic carcinoma cells). Possible human embryonic stem cell applications are described, with consideration of the desired cell line and the signals involved in their differentiation. The information about adult stem cells present - hemopoietic stem cells and the cells residing in selected tissues and organs: endothelium, pancreas, liver, epithelium, and gastrointestinal tract. Methods of their identification using the cell surfaces are also presented: the possibilities of in vitro transdifferentation, the phenomenon of in vivo plasticity, as well as morphological and genetic properties. Some topics of cell therapy and its clinical application in diabetics amplification are included. PMID:15114255

  11. Wnt signaling in adult intestinal stem cells and cancer.

    PubMed

    Krausova, Michaela; Korinek, Vladimir

    2014-03-01

    Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physiological range. In addition, the Wnt pathway involves various feedback loops that balance the opposing processes of cell proliferation and differentiation. Today, we have compelling evidence that mutations causing aberrant activation of the Wnt pathway promote expansion of undifferentiated progenitors and lead to cancer. The review summarizes recent advances in characterization of adult epithelial stem cells in the gut. We mainly focus on discoveries related to molecular mechanisms regulating the output of the Wnt pathway. Moreover, we present novel experimental approaches utilized to investigate the epithelial cell signaling circuitry in vivo and in vitro. Pivotal aspects of tissue homeostasis are often deduced from studies of tumor cells; therefore, we also discuss some latest results gleaned from the deep genome sequencing studies of human carcinomas of the colon and rectum. PMID:24308963

  12. Current Biosafety Considerations in Stem Cell Therapy.

    PubMed

    Mousavinejad, Masoumeh; Andrews, Peter W; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient's life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  13. Current Biosafety Considerations in Stem Cell Therapy

    PubMed Central

    Mousavinejad, Masoumeh; Andrews, Peter W.; Shoraki, Elham Kargar

    2016-01-01

    Stem cells can be valuable model systems for drug discovery and modelling human diseases as well as to investigate cellular interactions and molecular events in the early stages of development. Controlling the differentiation of stem cells into specific germ layers provides a potential source of highly specialized cells for therapeutic applications. In recent years, finding individual properties of stem cells such as their ultimate self-renewal capacity and the generation of particular cell lines by differentiation under specific culture conditions underpins the development of regenerative therapies. These futures make stem cells a leading candidate to treat a wide range of diseases. Nevertheless, as with all novel treatments, safety issues are one of the barriers that should be overcome to guarantee the quality of a patient’s life after stem cell therapy. Many studies have pointed to a large gap in our knowledge about the therapeutic applications of these cells. This gap clearly shows the importance of biosafety concerns for the current status of cell-based therapies, even more than their therapeutic efficacy. Currently, scientists report that tumorigenicity and immunogenicity are the two most important associated cell-based therapy risks. In principle, intrinsic factors such as cell characteristics and extrinsic elements introduced by manufacturing of stem cells can result in tumor formation and immunological reactions after stem cell transplantation. Therapeutic research shows there are many biological questions regarding safety issues of stem cell clinical applications. Stem cell therapy is a rapidly advancing field that needs to focus more on finding a comprehensive technology for assessing risk. A variety of risk factors (from intrinsic to extrinsic) should be considered for safe clinical stem cell therapies. PMID:27540533

  14. The asymmetric segregation of damaged proteins is stem cell-type dependent.

    PubMed

    Bufalino, Mary Rose; DeVeale, Brian; van der Kooy, Derek

    2013-05-13

    Asymmetric segregation of damaged proteins (DPs) during mitosis has been linked in yeast and bacteria to the protection of one cell from aging. Recent evidence suggests that stem cells may use a similar mechanism; however, to date there is no in vivo evidence demonstrating this effect in healthy adult stem cells. We report that stem cells in larval (neuroblast) and adult (female germline and intestinal stem cell) Drosophila melanogaster asymmetrically segregate DPs, such as proteins with the difficult-to-degrade and age-associated 2,4-hydroxynonenal (HNE) modification. Surprisingly, of the cells analyzed only the intestinal stem cell protects itself by segregating HNE to differentiating progeny, whereas the neuroblast and germline stem cells retain HNE during division. This led us to suggest that chronological life span, and not cell type, determines the amount of DPs a cell receives during division. Furthermore, we reveal a role for both niche-dependent and -independent mechanisms of asymmetric DP division. PMID:23649805

  15. Generation of new islets from stem cells.

    PubMed

    Roche, Enrique; Soria, Bernat

    2004-01-01

    Spain ranks number one in organ donors (35 per million per yr). Although the prevalence of diabetes is low (100,000 type 1 diabetic patients and 2 million type 2 diabetic patients), the expected number of patients receiving islet transplants should be estimated at 200 per year. Islet replacement represents a promising cure for diabetes and has been successfully applied in a limited number of type 1 diabetic patients, resulting in insulin independence for periods longer than 3 yr. However, it has been difficult to obtain sufficient numbers of islets from cadaveric donors. Interesting alternatives include acquiring renewable sources of cells using either embryonic or adult stem cells to overcome the islet scarcity problem. Stem cells are capable of extensive proliferation rates and are capable of differentiating into other cell types of the body. In particular, totipotent stem cells are capable of differentiating into all cell types in the body, whereas pluripotent stem cells are limited to the development of a certain number of differentiated cell types. Insulin-producing cells have been obtained from both embryonic and adult stem cells using several approaches. In animal models of diabetes, the therapeutic application of bioengineered insulin-secreting cells derived from stem cells has delivered promising results. This review will summarize the different approaches that have been used to obtain insulin-producing cells from embryonic and adult stem cells and highlights the key points that will allow in vitro differentiation and subsequent transplantation in the future. PMID:15289648

  16. Endometrial stem/progenitor cells: the first 10 years

    PubMed Central

    Gargett, Caroline E.; Schwab, Kjiana E.; Deane, James A.

    2016-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstrual blood stem cells' until December 2014. RESULTS Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44+ cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146+PDGFRβ+ (platelet-derived growth factor receptor beta) and SUSD2+ (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2+ cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman

  17. The biology of head and neck cancer stem cells

    PubMed Central

    Zhang, Zhaocheng; Filho, Manoel Sant´ Ana; Nör, Jacques E.

    2011-01-01

    Emerging evidence indicates that a small population of cancer cells is highly tumorigenic, endowed with self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the “drivers” of the tumorigenic process in some tumor types, and have been named cancer stem cells. Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. Cancer stem cells have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. The head and neck cancer stem cells reside primarily in perivascular niches in the invasive front where endothelial-cell initiated events contribute to their survival and function. In this review, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells to head and neck tumor progression. PMID:22070916

  18. Nonclinical safety strategies for stem cell therapies

    SciTech Connect

    Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  19. Adult stem-like cells in kidney.

    PubMed

    Hishikawa, Keiichi; Takase, Osamu; Yoshikawa, Masahiro; Tsujimura, Taro; Nangaku, Masaomi; Takato, Tsuyoshi

    2015-03-26

    Human pluripotent cells are promising for treatment for kidney diseases, but the protocols for derivation of kidney cell types are still controversial. Kidney tissue regeneration is well confirmed in several lower vertebrates such as fish, and the repair of nephrons after tubular damages is commonly observed after renal injury. Even in adult mammal kidney, renal progenitor cell or system is reportedly presents suggesting that adult stem-like cells in kidney can be practical clinical targets for kidney diseases. However, it is still unclear if kidney stem cells or stem-like cells exist or not. In general, stemness is defined by several factors such as self-renewal capacity, multi-lineage potency and characteristic gene expression profiles. The definite use of stemness may be obstacle to understand kidney regeneration, and here we describe the recent broad findings of kidney regeneration and the cells that contribute regeneration. PMID:25815133

  20. Designing Biomaterials To Direct Stem Cell Fate

    PubMed Central

    Cha, Chaenyung; Liechty, William B.; Khademhosseini, Ali; Peppas, Nicholas A.

    2012-01-01

    As stem cells are a cornerstone of regenerative medicine, research efforts have been extensively focused on controlling their self-renewal and differentiation. It is well known that stem cells are tightly regulated by a combination of physical and chemical factors from their complex extracellular surroundings; thus, conventional cell culture approaches based purely on using soluble factors to direct stem cell fate have resulted in limited success. To account for the complexities of native stem-cell niches, biomaterials are actively investigated as artificial extracellular matrices in order to mimic the natural microenvironment. This Perspective highlights important areas related to the design of biomaterials to control stem cell behavior, such as cell-responsive ligands, mechanical signals, and delivery of soluble factors. PMID:23136849

  1. Designing biomaterials to direct stem cell fate.

    PubMed

    Cha, Chaenyung; Liechty, William B; Khademhosseini, Ali; Peppas, Nicholas A

    2012-11-27

    As stem cells are a cornerstone of regenerative medicine, research efforts have been extensively focused on controlling their self-renewal and differentiation. It is well-known that stem cells are tightly regulated by a combination of physical and chemical factors from their complex extracellular surroundings; thus, conventional cell culture approaches based purely on using soluble factors to direct stem cell fate have resulted in limited success. To account for the complexities of native stem-cell niches, biomaterials are actively investigated as artificial extracellular matrices in order to mimic the natural microenvironment. This Perspective highlights important areas related to the design of biomaterials to control stem cell behavior, such as cell-responsive ligands, mechanical signals, and delivery of soluble factors. PMID:23136849

  2. Stem Cell Transplantation for Pulpal Regeneration: A Systematic Review.

    PubMed

    Fawzy El-Sayed, Karim M; Jakusz, Kimberley; Jochens, Arne; Dörfer, Christof; Schwendicke, Falk

    2015-10-01

    For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp-dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp-dentin complex regeneration. Studies quantitatively comparing pulp-dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35-4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39-8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp-dentin complex regeneration in animal models

  3. CLINICAL PROGRAMS OF STEM CELL THERAPIES FOR LIVER AND PANCREAS

    PubMed Central

    Lanzoni, Giacomo; Oikawa, Tsunekazu; Wang, Yunfang; Cui, Cai-Bin; Carpino, Guido; Cardinale, Vincenzo; Gerber, David; Gabriel, Mara; Dominguez-Bendala, Juan; Furth, Mark E.; Gaudio, Eugenio; Alvaro, Domenico; Inverardi, Luca; Reid, Lola M.

    2013-01-01

    Regenerative medicine is transitioning into clinical programs utilizing stem/progenitor cell therapies for repair of damaged organs. We summarize those for liver and pancreas, organs that share endodermal stem cell populations, biliary tree stem cells (hBTSCs), located in peribiliary glands: they are precursors to hepatic stem/progenitors in canals of Hering and to committed progenitors in pancreatic duct glands. They give rise to maturational lineages along a radial axis within bile duct walls and a proximal-to-distal axis starting at the duodenum and ending with mature cells in the liver or pancreas. Clinical trials have been ongoing for years assessing effects of fetal-liver-derived hepatic stem/progenitors transplanted into the hepatic artery of patients with various liver diseases. Immunosuppression was not required. Control subjects, those given standard of care for a given condition, all died within a year or deteriorated in their liver functions. Subjects transplanted with 100–150 million hepatic stem/progenitor cells had improved liver functions and survival extending for several years. Full evaluations of safety and efficacy of transplants are still in progress. Determined stem cell therapies for diabetes utilizing hBTSCs remain to be explored but are likely to occur following ongoing preclinical studies. In addition, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being used for patients with chronic liver conditions or with diabetes. MSCs have demonstrated significant effects through paracrine signaling of trophic and immune-modulatory factors, and there is limited evidence for inefficient lineage restriction into mature parenchymal or islet cells. HSCs’ effects are primarily via modulation of immune mechanisms. PMID:23873634

  4. Anchoring stem cells in the niche by cell adhesion molecules

    PubMed Central

    2009-01-01

    Adult stem cells generally reside in supporting local micro environments or niches, and intimate stem cell and niche association is critical for their long-term maintenance and function. Recent studies in model organisms especially Drosophila have started to unveil the underlying mechanisms of stem anchorage in the niche at the molecular and cellular level. Two types of cell adhesion molecules are emerging as essential players: cadherin-mediated cell adhesion for keeping stem cells within stromal niches, whereas integrin-mediated cell adhesion for keeping stem cells within epidermal niches. Further understanding stem cell anchorage and release in coupling with environmental changes should provide further insights into homeostasis control in tissues that harbor stem cells. PMID:19421010

  5. Cancer stem cells in glioblastoma

    PubMed Central

    Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.; Valentim, Claudia L.L.; Rich, Jeremy N.

    2015-01-01

    Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial. PMID:26109046

  6. Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells.

    PubMed

    Croft, Adam P; Przyborski, Stefan A

    2009-04-01

    The neurogenic response to injury in the postnatal brain is limited and insufficient for restoration of function. Recent evidence suggests that transplantation of mesenchymal stem cells (MSCs) into the injured brain is associated with improved functional recovery, mediated in part through amplification in the endogenous neurogenic response to injury. In the current study we investigate the interactions between bone marrow-derived MSCs and embryonic neural stem cells (NSCs) plus their differentiated progeny using an in vitro co-culture system. Two populations of MSCs were used, MSCs induced to express neural antigens (nestin+, Tuj-1+, GFAP+) and neural antigen negative MSCs. Following co-culture of induced MSCs with differentiating NSC/progenitor cells a significant increase in Tuj-1+ neurons was detected compared to co-cultures of non-induced MSCs in which an increase in astrocyte (GFAP+) differentiation was observed. The effect was mediated by soluble interactions between the two cell populations and was independent of any effect on cell death and proliferation. Induced and non-induced MSCs also promoted the survival of Tuj-1+ cell progeny in long-term cultures and both promoted axonal growth, an effect also seen in differentiating neuroblastoma cells. Therefore, MSCs provide instructive signals that are able to direct the differentiation of NSCs and promote axonal development in neuronal progeny. The data indicates that the nature of MSC derived signals is dependent not only on their microenvironment but on the developmental status of the MSCs. Pre-manipulation of MSCs prior to transplantation in vivo may be an effective means of enhancing the endogenous neurogenic response to injury. PMID:19159625

  7. Mesenchymal stem cells for cardiac cell therapy.

    PubMed

    Choi, Yeong-Hoon; Kurtz, Andreas; Stamm, Christof

    2011-01-01

    Despite refinements of medical and surgical therapies, heart failure remains a fatal disease. Myocardial infarction is the most common cause of heart failure, and only palliative measures are available to relieve symptoms and prolong the patient's life span. Because mammalian cardiomyocytes irreversibly exit the cell cycle at about the time of birth, the heart has traditionally been considered to lack any regenerative capacity. This paradigm, however, is currently shifting, and the cellular composition of the myocardium is being targeted by various regeneration strategies. Adult progenitor and stem cell treatment of diseased human myocardium has been carried out for more than 10 years (Menasche et al., 2001; Stamm et al., 2003), and it has become clear that, in humans, the regenerative capacity of hematopoietic stem cells and endothelial progenitor cells, despite potent proangiogenic effects, is limited (Stamm et al., 2009). More recently, mesenchymal stem cells (MSCs) and related cell types are being evaluated in preclinical models of heart disease as well as in clinical trials (see Published Clinical Trials, below). MSCs have the capacity to self-renew and to differentiate into lineages that normally originate from the embryonic mesenchyme (connective tissues, blood vessels, blood-related organs) (Caplan, 1991; Prockop, 1997; Pittenger et al., 1999). The current definition of MSCs includes plastic adherence in cell culture, specific surface antigen expression (CD105(+)/CD90(+)/CD73(+), CD34(-)/CD45(-)/CD11b(-) or CD14(-)/CD19(-) or CD79α(-)/HLA-DR1(-)), and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic) (Dominici et al., 2006 ). If those criteria are not met completely, the term "mesenchymal stromal cells" should be used for marrow-derived adherent cells, or other terms for MSC-like cells of different origin. For the purpose of this review, MSCs and related cells are discussed in general, and cell type

  8. Transforming ocular surface stem cell research into successful clinical practice

    PubMed Central

    Sangwan, Virender S; Jain, Rajat; Basu, Sayan; Bagadi, Anupam B; Sureka, Shraddha; Mariappan, Indumathi; MacNeil, Sheila

    2014-01-01

    It has only been a quarter of a century since the discovery of adult stem cells at the human corneo-scleral limbus. These limbal stem cells are responsible for generating a constant and unending supply of corneal epithelial cells throughout life, thus maintaining a stable and uniformly refractive corneal surface. Establishing this hitherto unknown association between ocular surface disease and limbal dysfunction helped usher in therapeutic approaches that successfully addressed blinding conditions such as ocular burns, which were previously considered incurable. Subsequent advances in ocular surface biology through basic science research have translated into innovations that have made the surgical technique of limbal stem cell transplantation simpler and more predictable. This review recapitulates the basic biology of the limbus and the rationale and principles of limbal stem cell transplantation in ocular surface disease. An evidence-based algorithm is presented, which is tailored to clinical considerations such as laterality of affliction, severity of limbal damage and concurrent need for other procedures. Additionally, novel findings in the form of factors influencing the survival and function of limbal stem cells after transplantation and the possibility of substituting limbal cells with epithelial stem cells of other lineages is also discussed. Finally this review focuses on the future directions in which both basic science and clinical research in this field is headed. PMID:24492499

  9. Lack of Phenotypical and Morphological Evidences of Endothelial to Hematopoietic Transition in the Murine Embryonic Head during Hematopoietic Stem Cell Emergence

    PubMed Central

    Iizuka, Kazuhide; Yokomizo, Tomomasa; Watanabe, Naoki; Tanaka, Yosuke; Osato, Motomi; Takaku, Tomoiku; Komatsu, Norio

    2016-01-01

    During mouse ontogeny, hematopoietic cells arise from specialized endothelial cells, i.e., the hemogenic endothelium, and form clusters in the lumen of arterial vessels. Hemogenic endothelial cells have been observed in several embryonic tissues, such as the dorsal aorta, the placenta and the yolk sac. Recent work suggests that the mouse embryonic head also produces hematopoietic stem cells (HSCs)/progenitors. However, a histological basis for HSC generation in the head has not yet been determined because the hematopoietic clusters and hemogenic endothelium in the head region have not been well characterized. In this study, we used whole-mount immunostaining and 3D confocal reconstruction techniques to analyze both c-Kit+ hematopoietic clusters and Runx1+ hemogenic endothelium in the whole-head vasculature. The number of c-Kit+ hematopoietic cells was 20-fold less in the head arteries than in the dorsal aorta. In addition, apparent nascent hematopoietic cells, which are characterized by a “budding” structure and a Runx1+ hemogenic endothelium, were not observed in the head. These results suggest that head HSCs may not be or are rarely generated from the endothelium in the same manner as aortic HSCs. PMID:27227884

  10. STEM CELL HOMING IN MUSCULOSKELETAL INJURY

    PubMed Central

    Fong, Li Shan E.; Chan, Casey K.; Goodman, Stuart B.

    2010-01-01

    The regenerative potential of injured adult tissue suggests the physiological existence of cells capable of participating in the reparative process. Recent studies indicate that stem-like cells residing in tissues contribute to tissue repair and are replenished by precursor bone marrow–derived cells. Mesenchymal stromal cells (MSC) are among the candidates for reparative cells. These cells can potentially be mobilized into the circulation in response to injury signals and exert their reparative effects at the site of injury. Current therapies for musculoskeletal injuries pose unavoidable risks which can impede full recovery. Trafficking of MSC to the injury site and their subsequent participation in the regenerative process is thought to be a natural healing response that can be imitated or augmented by enhancing the endogenous MSC pool with exogenously administered MSC. Therefore, a promising alternative to the existing strategies employed in the treatment of musculoskeletal injuries is to reinforce the inherent reparative capacity of the body by delivering MSC harvested from the patient’s own tissues to the site of injury. The aim of this review is to inform the reader of studies that have evaluated the intrinsic homing and regenerative abilities of MSC, with particular emphasis on the repair of musculoskeletal injuries. Research that supports the direct use of MSC (without in vitro differentiation into tissue-specific cells) will also be reported. Based on accruing evidence that the natural healing mechanism involves the recruitment of MSC and their subsequent reparative actions at the site of injury, as well as documented therapeutic response after the exogenous administration of MSC, the feasibility of the emerging strategy of instant stem-cell therapy will be proposed. PMID:20933277

  11. The adult human brain harbors multipotent perivascular mesenchymal stem cells.

    PubMed

    Paul, Gesine; Özen, Ilknur; Christophersen, Nicolaj S; Reinbothe, Thomas; Bengzon, Johan; Visse, Edward; Jansson, Katarina; Dannaeus, Karin; Henriques-Oliveira, Catarina; Roybon, Laurent; Anisimov, Sergey V; Renström, Erik; Svensson, Mikael; Haegerstrand, Anders; Brundin, Patrik

    2012-01-01

    Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain. PMID:22523602

  12. Fact or fiction - identifying the elusive multiple myeloma stem cell

    PubMed Central

    2013-01-01

    Multiple Myeloma (MM) is a debilitating disease of proliferating and malignant plasma cells that is currently incurable. The ability of monoclonal recurrence of disease suggests it might arise from a stem cell-like population capable of self-renewal. The difficulty to isolate the cancer stem-like cell in MM has introduced confusion toward this hypothesis. However, recent evidence has suggested that MM originates from the B cell lineage with memory-B cell like features, allowing for self-renewal of the progenitor-like status and differentiation to a monoclonal plasma cell population. Furthermore, this tumor-initiating cell uses signaling pathways and microenvironment similar to the hematopoietic stem cell, though hijacking these mechanisms to create and favor a more tumorigenic environment. The bone marrow niche allows for pertinent evasion, either through avoiding immunosurveillance or through direct interaction with the stroma, inducing quiescence and thus drug resistance. Understanding the interaction of the MM stem cell to the microenvironment and the mechanisms utilized by various stem cell-like populations to allow persistence and therapy-resistance can enable for better targeting of this cell population and potential eradication of the disease. PMID:24314019

  13. Enhancing spontaneous stem cell healing (Review)

    PubMed Central

    MAGUIRE, GREG; FRIEDMAN, PETER

    2014-01-01

    Adult stem cells are distributed throughout the human body and are responsible to a great extent for the body’s ability to maintain and heal itself. Accumulating data since the 1990s regarding stem cells have demonstrated that the beneficial effects of stem cells are not restricted to their ability to differentiate and are more likely due to their ability to release a multitude of molecules. Recent studies indicated that ≤80% of the therapeutic benefit of adult stem cells is manifested by the stem cell released molecules (SRM) rather than the differentiation of the stem cells into mature tissue. Stem cells may release potent combinations of factors that modulate the molecular composition of the cellular milieu to evoke a multitude of responses from neighboring cells. A multitude of pathways are involved in cellular and tissue function and, when the body is in a state of disease or trauma, a multitude of pathways are involved in the underlying mechanisms of that disease or trauma. Therefore, stem cells represent a natural systems-based biological factory for the production and release of a multitude of molecules that interact with the system of biomolecular circuits underlying disease or tissue damage. Currently, efforts are aimed at defining, stimulating, enhancing and harnessing SRM mechanisms, in order to develop systems-based methods for tissue regeneration, develop drugs/biologics or other therapeutics and enhance the release of SRM into the body for natural healing through proper dietary, exercise and other lifestyle strategies. PMID:24649089

  14. Glial cell derived neurotrophic factor induces spermatogonial stem cell marker genes in chicken mesenchymal stem cells.

    PubMed

    Boozarpour, Sohrab; Matin, Maryam M; Momeni-Moghaddam, Madjid; Dehghani, Hesam; Mahdavi-Shahri, Naser; Sisakhtnezhad, Sajjad; Heirani-Tabasi, Asieh; Irfan-Maqsood, Muhammad; Bahrami, Ahmad Reza

    2016-06-01

    Mesenchymal stem cells (MSCs) are known with the potential of multi-lineage differentiation. Advances in differentiation technology have also resulted in the conversion of MSCs to other kinds of stem cells. MSCs are considered as a suitable source of cells for biotechnology purposes because they are abundant, easily accessible and well characterized cells. Nowadays small molecules are introduced as novel and efficient factors to differentiate stem cells. In this work, we examined the potential of glial cell derived neurotrophic factor (GDNF) for differentiating chicken MSCs toward spermatogonial stem cells. MSCs were isolated and characterized from chicken and cultured under treatment with all-trans retinoic acid (RA) or glial cell derived neurotrophic factor. Expression analysis of specific genes after 7days of RA treatment, as examined by RT-PCR, proved positive for some germ cell markers such as CVH, STRA8, PLZF and some genes involved in spermatogonial stem cell maintenance like BCL6b and c-KIT. On the other hand, GDNF could additionally induce expression of POU5F1, and NANOG as well as other genes which were induced after RA treatment. These data illustrated that GDNF is relatively more effective in diverting chicken MSCs towards Spermatogonial stem cell -like cells in chickens and suggests GDNF as a new agent to obtain transgenic poultry, nevertheless, exploitability of these cells should be verified by more experiments. PMID:27026484

  15. Mesenchymal stem cells: From stem cells to sarcomas.

    PubMed

    Lye, Kwan Liang; Nordin, Norshariza; Vidyadaran, Sharmili; Thilakavathy, Karuppiah

    2016-06-01

    Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas. PMID:26992453

  16. Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation.

    PubMed

    Kanatsu-Shinohara, Mito; Toyokuni, Shinya; Morimoto, Takeshi; Matsui, Shigeyuki; Honjo, Tasuku; Shinohara, Takashi

    2003-05-01

    Spermatogenesis is dependent on a small population of stem cells. Although stem cells are believed to expand infinitely, there is little functional evidence regarding whether spermatogonial stem cells can increase in their number. Using the spermatogonial transplantation technique, we evaluated the proliferative potential of spermatogonial stem cells in two models of regeneration. After busulfan injection to deplete stem cells, the surviving stem cells were able to expand by at least 15.8-fold within 2 mo. On the other hand, a serial transplantation study indicated that one transplanted stem cell was able to expand by 3.8- and 12-fold within 2 and 4 mo, respectively. These results provide direct functional evidence for the expansion of stem cells and establish the basis for further characterization of the stem cell self-renewal process. PMID:12606387

  17. Transdifferentiation of Stem Cells: A Critical View

    NASA Astrophysics Data System (ADS)

    Gruh, Ina; Martin, Ulrich

    Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application of adult stem cells. Previously unknown possibilities of cell differentiation beyond the known commitment of a given stem cell have been described using keywords such as "blood to liver," or "bone to brain." Controversies on the likelihood, as well as the biological significance, of these conversions almost immediately arose within this young field of stem cell biology. This chapter will concentrate on these controversies and focus on selected examples demonstrating the technical aspects of stem cell transdifferentiation and the evaluation of the tools used to analyze these events.

  18. Metabolic regulation of stem cell function.

    PubMed

    Burgess, R J; Agathocleous, M; Morrison, S J

    2014-07-01

    Stem cell function is regulated by intrinsic mechanisms, such as transcriptional and epigenetic regulators, as well as extrinsic mechanisms, such as short-range signals from the niche and long-range humoral signals. Interactions between these regulatory mechanisms and cellular metabolism are just beginning to be identified. In multiple systems, differentiation is accompanied by changes in glycolysis, oxidative phosphorylation and the levels of reactive oxygen species. Indeed, metabolic pathways regulate proliferation and differentiation by regulating energy production and the generation of substrates for biosynthetic pathways. Some metabolic pathways appear to function differently in stem cells as compared with restricted progenitors and differentiated cells. They also appear to influence stem cell function by regulating signal transduction, epigenetic marks and oxidative stress. Studies to date illustrate the importance of metabolism in the regulation of stem cell function and suggest complex cross-regulation likely exists between metabolism and other stem cell regulatory mechanisms. PMID:24697828

  19. Epidermal Stem Cells in Orthopaedic Regenerative Medicine

    PubMed Central

    Li, Jin; Zhen, Gehua; Tsai, Shin-Yi; Jia, Xiaofeng

    2013-01-01

    In the last decade, great advances have been made in epidermal stem cell studies at the cellular and molecular level. These studies reported various subpopulations and differentiations existing in the epidermal stem cell. Although controversies and unknown issues remain, epidermal stem cells possess an immune-privileged property in transplantation together with easy accessibility, which is favorable for future clinical application. In this review, we will summarize the biological characteristics of epidermal stem cells, and their potential in orthopedic regenerative medicine. Epidermal stem cells play a critical role via cell replacement, and demonstrate significant translational potential in the treatment of orthopedic injuries and diseases, including treatment for wound healing, peripheral nerve and spinal cord injury, and even muscle and bone remodeling. PMID:23727934

  20. Signaling involved in stem cell reprogramming and differentiation

    PubMed Central

    Tanabe, Shihori

    2015-01-01

    Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have revealed that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell programming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review, the molecular interactions and signaling pathways related to stem cell differentiation are discussed. PMID:26328015

  1. Amniotic fluid stem cells prevent β-cell injury

    PubMed Central

    VILLANI, VALENTINA; MILANESI, ANNA; SEDRAKYAN, SARGIS; DA SACCO, STEFANO; ANGELOW, SUSANNE; CONCONI, MARIA TERESA; DI LIDDO, ROSA; DE FILIPPO, ROGER; PERIN, LAURA

    2015-01-01

    Background aims The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating β-cell injury and restoring β-cell function. Methods Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation. Results AFSC injection resulted in protection from β-cell damage and increased β-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, β-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining β-cell mass and function. Conclusions Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous β-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non–genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved. PMID:24210784

  2. Energy metabolism and energy-sensing pathways in mammalian embryonic and adult stem cell fate

    PubMed Central

    Rafalski, Victoria A.; Mancini, Elena; Brunet, Anne

    2012-01-01

    Summary Metabolism is influenced by age, food intake, and conditions such as diabetes and obesity. How do physiological or pathological metabolic changes influence stem cells, which are crucial for tissue homeostasis? This Commentary reviews recent evidence that stem cells have different metabolic demands than differentiated cells, and that the molecular mechanisms that control stem cell self-renewal and differentiation are functionally connected to the metabolic state of the cell and the surrounding stem cell niche. Furthermore, we present how energy-sensing signaling molecules and metabolism regulators are implicated in the regulation of stem cell self-renewal and differentiation. Finally, we discuss the emerging literature on the metabolism of induced pluripotent stem cells and how manipulating metabolic pathways might aid cellular reprogramming. Determining how energy metabolism regulates stem cell fate should shed light on the decline in tissue regeneration that occurs during aging and facilitate the development of therapies for degenerative or metabolic diseases. PMID:23420198

  3. Clonogenicity: holoclones and meroclones contain stem cells.

    PubMed

    Beaver, Charlotte M; Ahmed, Aamir; Masters, John R

    2014-01-01

    When primary cultures of normal cells are cloned, three types of colony grow, called holoclones, meroclones and paraclones. These colonies are believed to be derived from stem cells, transit-amplifying cells and differentiated cells respectively. More recently, this approach has been extended to cancer cell lines. However, we observed that meroclones from the prostate cancer cell line DU145 produce holoclones, a paradoxical observation as meroclones are thought to be derived from transit-amplifying cells. The purpose of this study was to confirm this observation and determine if both holoclones and meroclones from cancer cell lines contain stem cells. We demonstrated that both holoclones and meroclones can be serially passaged indefinitely, are highly proliferative, can self-renew to form spheres, are serially tumorigenic and express stem cell markers. This study demonstrates that the major difference between holoclones and meroclones derived from a cancer cell line is the proportion of stem cells within each colony, not the presence or absence of stem cells. These findings may reflect the properties of cancer as opposed to normal cells, perhaps indicating that the hierarchy of stem cells is more extensive in cancer. PMID:24587067

  4. Pathological modifications of plant stem cell destiny

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In higher plants, the shoot apex contains undifferentiated stem cells that give rise to various tissues and organs. The fate of these stem cells determines the pattern of plant growth as well as reproduction; and such fate is genetically preprogrammed. We found that a bacterial infection can derai...

  5. Stem Cell Research and Health Education

    ERIC Educational Resources Information Center

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2008-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the…

  6. 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

  7. 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. PMID:24970380

  8. Stem Cell Fate Is a Touchy Subject.

    PubMed

    Smith, Quinton; Gerecht, Sharon

    2016-09-01

    Uncoupling synergistic interactions between physio-chemical cues that guide stem cell fate may improve efforts to direct their differentiation in culture. Using supramolecular hydrogels, Alakpa et al. (2016) demonstrate that mesenchymal stem cell differentiation is paired to depletion of bioactive metabolites, which can be utilized to chemically induce osteoblast and chondrocyte fate. PMID:27588745

  9. Organ or Stem Cell Transplant and Your Mouth

    MedlinePlus

    ... Stem Cell Transplant and Your Mouth Organ or Stem Cell Transplant and Your Mouth Main Content Key Points​ ... Your Dentist Before Transplant Before an organ or stem cell transplant, have a dental checkup. Your mouth should ...

  10. Stem Cell Research: Unlocking the Mystery of Disease

    MedlinePlus

    ... Home Current Issue Past Issues From the Director: Stem Cell Research: Unlocking the Mystery of Disease Past ... Zerhouni, NIH Director, described the need for expanding stem cell research. Recently, he spoke about stem cell ...

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

    PubMed

    Van Pham, Phuc

    2016-01-01

    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. PMID:27121227

  12. Overcoming Multidrug Resistance in Cancer Stem Cells

    PubMed Central

    Moitra, Karobi

    2015-01-01

    The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC) transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed. PMID:26649310

  13. Artificial gametes from stem cells

    PubMed Central

    Moreno, Inmaculada; Míguez-Forjan, Jose Manuel

    2015-01-01

    The generation of artificial gametes is a real challenge for the scientific community today. In vitro development of human eggs and sperm will pave the way for the understanding of the complex process of human gametogenesis and will provide with human gametes for the study of infertility and the onset of some inherited disorders. However, the great promise of artificial gametes resides in their future application on reproductive treatments for all these people wishing to have genetically related children and for which gamete donation is now their unique option of parenthood. This is the case of infertile patients devoid of suitable gametes, same sex couples, singles and those fertile couples in a high risk of transmitting serious diseases to their progeny. In the search of the best method to obtain artificial gametes, many researchers have successfully obtained human germ cell-like cells from stem cells at different stages of differentiation. In the near future, this field will evolve to new methods providing not only viable but also functional and safe artificial germ cells. These artificial sperm and eggs should be able to recapitulate all the genetic and epigenetic processes needed for the correct gametogenesis, fertilization and embryogenesis leading to the birth of a healthy and fertile newborn. PMID:26161331

  14. Are stem cells a cure for diabetes?

    PubMed

    McCall, Michael D; Toso, Christian; Baetge, Emmanuel E; Shapiro, A M James

    2010-01-01

    With the already heightened demand placed on organ donation, stem cell therapy has become a tantalizing idea to provide glucose-responsive insulin-producing cells to Type 1 diabetic patients as an alternative to islet transplantation. Multiple groups have developed varied approaches to create a population of cells with the appropriate characteristics. Both adult and embryonic stem cells have received an enormous amount of attention as possible sources of insulin-producing cells. Although adult stem cells lack the pluripotent nature of their embryonic counterparts, they appear to avoid the ethical debate that has centred around the latter. This may limit the eventual application of embryonic stem cells, which have already shown promise in early mouse models. One must also consider the potential of stem cells to form teratomas, a complication which would prove devastating in an immunologically compromised transplant recipient. The present review looks at the progress to date in both the adult and embryonic stem cells fields as potential treatments for diabetes. We also consider some of the limitations of stem cell therapy and the potential complications that may develop with their use. PMID:19807695

  15. Spermatogonial stem cells: progress and prospects

    PubMed Central

    Komeya, Mitsuru; Ogawa, Takehiko

    2015-01-01

    Twenty years ago, the transplantation of spermatogonial stem cells (SSCs) from a mouse to other recipient mice was shown to be feasible, which clearly demonstrated the functional identity of SSCs. Since then, several important new findings and other technical developments have followed, which included a new hypothesis on their cell kinetics and spermatogonial hierarchy in the testis, a culture method allowing their self-renewal and proliferation, a testis tissue organ culture method, which induced their complete differentiation up to sperm, and the in vitro induction of germ cells from embryonic stem cells and induced pluripotent stem cells. These advancements reinforced or advanced our understanding of this unique cell. Nonetheless, there are many unresolved questions in the study of spermatogonial stem cells and a long road remains until these cells can be used clinically in reproductive medicine. PMID:25994650

  16. 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

  17. Spermatogonial stem cells: Progress and prospects.

    PubMed

    Komeya, Mitsuru; Ogawa, Takehiko

    2015-01-01

    Twenty years ago, the transplantation of spermatogonial stem cells (SSCs) from a mouse to other recipient mice was shown to be feasible, which clearly demonstrated the functional identity of SSCs. Since then, several important new findings and other technical developments have followed, which included a new hypothesis on their cell kinetics and spermatogonial hierarchy in the testis, a culture method allowing their self-renewal and proliferation, a testis tissue organ culture method, which induced their complete differentiation up to sperm, and the in vitro induction of germ cells from embryonic stem cells and induced pluripotent stem cells. These advancements reinforced or advanced our understanding of this unique cell. Nonetheless, there are many unresolved questions in the study of spermatogonial stem cells and a long road remains until these cells can be used clinically in reproductive medicine. PMID:25994650

  18. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy.

    PubMed

    Ding, Dah-Ching; Chang, Yu-Hsun; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2015-01-01

    The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton's jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications. PMID:25622293

  19. Breast cancer stem cells and radiation

    NASA Astrophysics Data System (ADS)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1

  20. Stem Cells for Cutaneous Wound Healing

    PubMed Central

    Kirby, Giles T. S.; Mills, Stuart J.; Cowin, Allison J.; Smith, Louise E.

    2015-01-01

    Optimum healing of a cutaneous wound involves a well-orchestrated cascade of biological and molecular processes involving cell migration, proliferation, extracellular matrix deposition, and remodelling. When the normal biological process fails for any reason, this healing process can stall resulting in chronic wounds. Wounds are a growing clinical burden on healthcare systems and with an aging population as well as increasing incidences of obesity and diabetes, this problem is set to increase. Cell therapies may be the solution. A range of cell based approaches have begun to cross the rift from bench to bedside and the supporting data suggests that the appropriate administration of stem cells can accelerate wound healing. This review examines the main cell types explored for cutaneous wound healing with a focus on clinical use. The literature overwhelmingly suggests that cell therapies can help to heal cutaneous wounds when used appropriately but we are at risk of clinical use outpacing the evidence. There is a need, now more than ever, for standardised methods of cell characterisation and delivery, as well as randomised clinical trials. PMID:26137471

  1. Stem cell trials for cardiovascular medicine: ethical rationale.

    PubMed

    Niemansburg, Sophie L; Teraa, Martin; Hesam, Husna; van Delden, Johannes J M; Verhaar, Marianne C; Bredenoord, Annelien L

    2014-10-01

    Stem cell-based interventions provide new treatment prospects for many disease conditions, including cardiovascular disorders. Clinical trials are necessary to collect adequate evidence on (long-term) safety and efficacy of novel interventions such as stem cells, but the design and launch of clinical trials, from first-in-human studies to larger randomized controlled trials (RCTs), is scientifically and ethically challenging. Stem cells are different from traditional pharmaceuticals, surgical procedures, and medical devices in the following ways: the novelty and complexity of stem cells, the invasiveness of the procedures, and the novel aim of regeneration. These specifics, combined with the characteristics of the study population, will have an impact on the design and ethics of RCTs. The recently closed JUVENTAS trial will serve as an example to identify the (interwoven) scientific and ethical challenges in the design and launch of stem cell RCTs. The JUVENTAS trial has investigated the efficacy of autologous bone marrow cells in end-stage vascular patients, in a double-blind sham-controlled design. We first describe the choices, considerations, and experiences of the JUVENTAS team. Subsequently, we identify the main ethical and scientific challenges and discuss what is important to consider in the design of future stem cell RCTs: assessment of risks and benefits, the choice for outcome measures, the choice for the comparator, the appropriate selection of participants, and adequate informed consent. Additionally, the stem cell field is highly in the spotlight due to the (commercial) interests and expectations. This warrants a cautious pace of translation and scrupulous set up of clinical trials, as failures could put the field in a negative light. At the same time, knowledge from clinical trials is necessary for the field to progress. We conclude that in the scientifically and ethically challenging field of stem cell RCTs, researchers and clinicians have to

  2. Mesenchymal stem cells in pathogenesis of myelodysplastic syndromes

    PubMed Central

    Wang, Jingya

    2014-01-01

    Myelodysplastic syndromes (MDS) are clonal malignant stem cell disorders characterized by inefficient hematopoiesis. The role of the marrow microenvironment in the pathogenesis of the disease has been controversial. Emerging evidence indicated that mesenchymal stem cells (MSC) derived from MDS patients were cytogenetically abnormal, and they showed a deficient hematopoietic-supportive capacity and increased production of cytokine such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon γ (IFN-γ). From the point of some evidence, the abnormal microenvironment seems to participate in the progression of the disease by contributing to the selective expansion of the malignant clone. In this review, we will discuss the most recent progress related to identification of normal MSC and the importance of the stem cell niche in development and maintenance of MDS.

  3. Non-coding RNAs Functioning in Colorectal Cancer Stem Cells.

    PubMed

    Fanale, Daniele; Barraco, Nadia; Listì, Angela; Bazan, Viviana; Russo, Antonio

    2016-01-01

    In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identified in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT). PMID:27573896

  4. Orosphere Assay: A method for propagation of head and neck cancer stem cells

    PubMed Central

    Krishnamurthy, Sudha; Nör, Jacques E.

    2014-01-01

    Background Recent evidence suggests that head and neck squamous cell carcinomas (HNSCC) harbor a small sub-population of highly tumorigenic cells, named cancer stem cells. A limiting factor in cancer stem cell research is the intrinsic difficulty of expanding cells in an undifferentiated state in vitro. Methods Here, we describe the development of the orosphere assay, a method for the study of putative head and neck cancer stem cells. An orosphere is defined as a non-adherent colony of cells sorted from primary HNSCC or from HNSCC cell lines and cultured in 3-D soft agar or ultra-low attachment plates. Aldehyde dehydrogenase (ALDH) activity and CD44 expression were used here as stem cell markers. Results This assay allowed for the propagation of head and neck cancer cells that retained stemness and self-renewal. Conclusion The orosphere assay is well suited for studies designed to understand the pathobiology of head and neck cancer stem cells. PMID:22791367

  5. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches.

    PubMed

    Akram, Khondoker M; Patel, Neil; Spiteri, Monica A; Forsyth, Nicholas R

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  6. Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

    PubMed Central

    Akram, Khondoker M.; Patel, Neil; Spiteri, Monica A.; Forsyth, Nicholas R.

    2016-01-01

    The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases. PMID:26797607

  7. Regulation of the adrenocortical stem cell niche: implications for disease

    PubMed Central

    Walczak, Elisabeth M.; Hammer, Gary D.

    2015-01-01

    Stem cells are endowed with the potential for self-renewal and multipotency. Pluripotent embryonic stem cells have an early role in the formation of the three germ layers (ectoderm, mesoderm and endoderm), whereas adult tissue stem cells and progenitor cells are critical mediators of organ homeostasis. The adrenal cortex is an exceptionally dynamic endocrine organ that is homeostatically maintained by paracrine and endocrine signals throughout postnatal life. In the past decade, much has been learned about the stem and progenitor cells of the adrenal cortex and the multiple roles that these cell populations have in normal development and homeostasis of the adrenal gland and in adrenal diseases. In this Review, we discuss the evidence for the presence of adrenocortical stem cells, as well as the various signalling molecules and transcriptional networks that are critical for the embryological establishment and postnatal maintenance of this vital population of cells. The implications of these pathways and cells in the pathophysiology of disease are also addressed. PMID:25287283

  8. Breast cancer stem cells, pathways and therapeutic perspectives 2011.

    PubMed

    Nigam, Anjana

    2013-06-01

    The evidence for the existence of a heterogeneous population of cancer stem cells (CSCs) responsible for the initiation and maintenance of cancer has been characterized for several tumors recently. Purification and molecular characterization of normal human mammary stem cells from cultured mammospheres has been achieved, providing evidence supporting a model in which breast tumor heterogeneity is a reflection of a number of CSC-like cells in the tumor. A number of experimental methodologies have been developed to characterize epithelial stem cells, including the expression of cell surface or intracellular markers, mammosphere formation, exclusion of fluorescent dye by a side population, retention of the radionucleotide label, etc. Methodologies have also been successfully employed to identify tumorigenic cells within breast cancers. The most important characteristics of stem cells are the capacity for self-renewal and the regulation of the balance between self-renewal and differentiation. In the mammary gland, signaling pathways, such as Hedgehog (Hh), Wnt/β-catenin, and Notch, play a role in embryogenesis and organogenesis and maintenance of tissues in the adult through regulation of the balance between self-renewal and differentiation of stem cells. Breast TAAs include epitopes from proteins, such as carcinoembryonic antigen and NYBR-1, which are involved in tissue differentiation. Targeting BCSCs may be achieved by a number of approaches such as chemotherapy sensitization of BCSCs, differentiating therapy, targeting stem cell elimination, targeting signaling pathways and drug transporters, and inhibition of regulatory pathways involved in self-renewal. Targeting cells which have the potential to metastasize will be an important aspect of the BCSC field as these are the cells that cause the majority of morbidity and mortality from breast cancer. PMID:24426422

  9. Optical quantification of forces at play during stem cell differentiation

    NASA Astrophysics Data System (ADS)

    Ritter, Christine M.; Brickman, Joshua M.; Oddershede, Lene B.

    2016-03-01

    A cell is in constant interaction with its environment, it responds to external mechanical, chemical and biological signals. The response to these signals can be of various nature, for instance intra-cellular mechanical re-arrangements, cell-cell interactions, or cellular reinforcements. Optical methods are quite attractive for investigating the mechanics inside living cells as, e.g., optical traps are amongst the only nanotools that can reach and manipulate, measure forces, inside a living cell. In the recent years it has become increasingly evident that not only biochemical and biomolecular cues, but also that mechanical ones, play an important roles in stem cell differentiation. The first evidence for the importance of mechanical cues emerged from studies showing that substrate stiffness had an impact on stem cell differentiation. Recently, techniques such as optical tweezers and stretchers have been applied to stem cells, producing new insights into the role of mechanics in regulating renewal and differentiation. Here, we describe how optical tweezers and optical stretchers can be applied as a tool to investigate stem cell mechanics and some of the recent results to come out of this work.

  10. Preconditioning Strategy in Stem Cell Transplantation Therapy

    PubMed Central

    Yu, Shan Ping; Wei, Zheng; Wei, Ling

    2013-01-01

    Stem cell transplantation therapy has emerged as a promising regenerative medicine for ischemic stroke and other neurodegenerative disorders. However, many issues and problems remain to be resolved before successful clinical applications of the cell-based therapy. To this end, some recent investigations have sought to benefit from well-known mechanisms of ischemic/hypoxic preconditioning. Ischemic/hypoxic preconditioning activates endogenous defense mechanisms that show marked protective effects against multiple insults found in ischemic stroke and other acute attacks. As in many other cell types, a sub-lethal hypoxic exposure significantly increases the tolerance and regenerative properties of stem cells and progenitor cells. So far, a variety of preconditioning triggers have been tested on different stem cells and progenitor cells. Preconditioned stem cells and progenitors generally show much better cell survival, increased neuronal differentiation, enhanced paracrine effects leading to increased trophic support, and improved homing to the lesion site. Transplantation of preconditioned cells helps to suppress inflammatory factors and immune responses, and promote functional recovery. Although the preconditioning strategy in stem cell therapy is still an emerging research area, accumulating information from reports over the last few years already indicates it as an attractive, if not essential, prerequisite for transplanted cells. It is expected that stem cell preconditioning and its clinical applications will attract more attention in both the basic research field of preconditioning as well as in the field of stem cell translational research. This review summarizes the most important findings in this active research area, covering the preconditioning triggers, potential mechanisms, mediators, and functional benefits for stem cell transplant therapy. PMID:23914259

  11. The NF-κB Pathway and Cancer Stem Cells

    PubMed Central

    Rinkenbaugh, Amanda L.; Baldwin, Albert S.

    2016-01-01

    The NF-κB transcription factor pathway is a crucial regulator of inflammation and immune responses. Additionally, aberrant NF-κB signaling has been identified in many types of cancer. Downstream of key oncogenic pathways, such as RAS, BCR-ABL, and Her2, NF-κB regulates transcription of target genes that promote cell survival and proliferation, inhibit apoptosis, and mediate invasion and metastasis. The cancer stem cell model posits that a subset of tumor cells (cancer stem cells) drive tumor initiation, exhibit resistance to treatment, and promote recurrence and metastasis. This review examines the evidence for a role for NF-κB signaling in cancer stem cell biology. PMID:27058560

  12. Stem cells: therapeutic present and future.

    PubMed

    Khurdayan, Valeria K

    2007-03-01

    Ever since the first embryonic stem cells were isolated in the 1990s scientists and clinicians as well as the general public have followed the development of the field with great attention. As unspecialized cells capable of dividing, renewing and differentiating into specialized cells, stem cells hold great promise as a therapeutic strategy for many diseases, especially those of degenerative nature. In 2006, stem cells were actively investigated in preclinical and clinical settings to manage heart failure, amyotrophic lateral sclerosis, spinal cord injury, stroke, hematologic disorders, renal cell carcinoma, solid tumor cancer, Crohn's disease and cirrhosis, among other disorders. Likewise, biotech and pharmaceutical industry highlighted stem cells and associated products and technologies as useful tools for drug discovery that provide relevant clinical models and ensure efficacious transition of investigational compounds into preclinical testing. PMID:17440635

  13. Differentiation of hepatocytes from pluripotent stem cells

    PubMed Central

    Mallanna, Sunil K.

    2014-01-01

    Differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells into hepatocyte-like cells provides a platform to study the molecular basis of human hepatocyte differentiation, to develop cell culture models of liver disease, and to potentially provide hepatocytes for treatment of end-stage liver disease. Additionally, hepatocyte-like cells generated from human pluripotent stem cells could serve as platforms for drug discovery, determination of pharmaceutical induced hepatotoxicity, and evaluation of idiosyncratic drug-drug interactions. Here, we describe a step-wise protocol previously developed in our laboratory that facilitates the highly efficient and reproducible differentiation of human pluripotent stem cells into hepatocyte-like cells. Our protocol uses defined culture conditions and closely recapitulates key developmental events that are found to occur during hepatogenesis. PMID:24510789

  14. Tissue-Derived Stem and Progenitor Cells

    PubMed Central

    Tesche, Leora J.; Gerber, David A.

    2010-01-01

    The characterization and isolation of various stem cell populations, from embryonic through tissue-derived stem cells, have led a rapid growth in the field of stem cell research. These research efforts have often been interrelated as to the markers that identify a select cell population are frequently analyzed to determine their expression in cells of distinct organs/tissues. In this review, we will expand the current state of research involving select tissue-derived stem cell populations including the liver, central nervous system, and cardiac tissues as examples of the success and challenges in this field of research. Lastly, the challenges of clinical therapies will be discussed as it applies to these unique cell populations. PMID:21048854

  15. 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. PMID:26367485

  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. Speculation on the evolution of stem cells.

    PubMed

    Shostak, Stanley

    2008-01-01

    Profoundly different patterns of potency and division are exhibited by mammalian embryonic and adult stem cells. Additional confusion surrounds stem-cell surrogates, cache and reserve cells having some characteristics of stem cells and not others. Mystification may have been introduced historically with the concepts of determinate and regulative development, but, hopefully, the muddle can be resolved by tracing the evolution of stem cells in Metazoa. Blastomeres in marine sponges, cnidarians, lophotrochozoans, small ecdysozoans (e.g., Caenorhabditis elegans), and some deuterostomes (e.g., echinoderms and ascidians) exhibit determinative development. Their larval and adult cells have narrow potencies, sometimes coupled to virtually unlimited proliferation, and function in the growth, maintenance and regulation of body size. The embryos of larger arthropods and deuterostomes with well-provisioned eggs or viviparity, on the other hand, exhibit regulative development, while their larval "set-aside" or adult stem cells function in the growth, maintenance, and regulation of organ size coupled to constrained proliferation and cell turnover. Mammalian embryonic stem cells would seem adapted to rapid proliferation, functioning in part to enclose yolk or to acquire access to maternal resources. The cellular products of embryonic stem cells routinely come under global influences and give rise to the cells of germ layers and organ rudiments. Mammalian adult stem cells resemble the blastomeres of planktonic and benthic organisms with small eggs and may have evolved in mature organisms as an adaptation to the growth and maintenance of tissues via proliferation and the regulation of organ size via cell loss (e.g., terminal differentiation). Cancer stem cells, instrumental in metastasis, would seem to ignore mechanisms normally functioning in the removal of excess cells. Strategies for regenerative therapies in adult mammals, therefore, might be based on stimulating growth of

  18. Current understanding concerning intestinal stem cells.

    PubMed

    Cui, Shuang; Chang, Peng-Yu

    2016-08-21

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  19. 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

  20. Stem cell applications in military medicine

    PubMed Central

    2011-01-01

    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. PMID:22011454

  1. Current understanding concerning intestinal stem cells

    PubMed Central

    Cui, Shuang; Chang, Peng-Yu

    2016-01-01

    In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same. PMID:27610020

  2. Stem cells of the beetle midgut epithelium.

    PubMed

    Nardi, James B; Bee, Charles Mark; Miller, Lou Ann

    2010-03-01

    At the completion of metamorphosis, adult insect cells have traditionally been assumed to halt cell divisions and terminally differentiate. While this model of differentiation holds for adult ectodermal epithelia that secrete cuticular specializations of exoskeletons, adult endodermal epithelia are populated by discrete three-dimensional aggregates of stem cells that continue to divide and differentiate after adult emergence. Aggregates of these presumptive adult stem cells are scattered throughout larval and pupal midgut monolayers. At the beginning of adult development (pupal-adult apolysis), the number of cells within each aggregate begins to increase rapidly. Dividing cells form three-dimensional, coherent populations that project as regenerative pouches of stem cells into the hemocoel surrounding the midgut. Stem cell pouches are regularly spaced throughout endodermal monolayers, having adopted a spacing pattern suggesting that each incipient pouch inhibits the formation of a similar pouch within a certain radius of itself-a process referred to as lateral inhibition. At completion of adult development (pupal-adult ecdysis), a distinct basal-luminal polarity has been established within each regenerative pouch. Dividing stem cells occupying the basal region are arranged in three-dimensional aggregates. As these are displaced toward the lumen, they transform into two-dimensional monolayers of differentiated epithelial cells whose apical surfaces are covered by microvilli. This organization of stem cell pouches in insect midguts closely parallels that of regenerative crypts in mammalian intestines. PMID:19909756

  3. Multipotent somatic stem cells contribute to the stem cell niche in the Drosophila testis.

    PubMed

    Voog, Justin; D'Alterio, Cecilia; Jones, D Leanne

    2008-08-28

    Adult stem cells reside in specialized microenvironments, or niches, that have an important role in regulating stem cell behaviour. Therefore, tight control of niche number, size and function is necessary to ensure the proper balance between stem cells and progenitor cells available for tissue homeostasis and wound repair. The stem cell niche in the Drosophila male gonad is located at the tip of the testis where germline and somatic stem cells surround the apical hub, a cluster of approximately 10-15 somatic cells that is required for stem cell self-renewal and maintenance. Here we show that somatic stem cells in the Drosophila testis contribute to both the apical hub and the somatic cyst cell lineage. The Drosophila orthologue of epithelial cadherin (DE-cadherin) is required for somatic stem cell maintenance and, consequently, the apical hub. Furthermore, our data indicate that the transcriptional repressor escargot regulates the ability of somatic cells to assume and/or maintain hub cell identity. These data highlight the dynamic relationship between stem cells and the niche and provide insight into genetic programmes that regulate niche size and function to support normal tissue homeostasis and organ regeneration throughout life. PMID:18641633

  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. PMID:26222885

  5. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed. PMID:23097262

  6. The Endocrine Regulation of Stem Cells: Physiological Importance and Pharmacological Potentials for Cell-Based Therapy.

    PubMed

    Ghorbani, Ahmad; Naderi-Meshkin, Hojjat

    2016-01-01

    Throughout life, different types of stem cells participate in tissue generation, maintenance, plasticity, and repair. Their abilities to secrete growth factors, to proliferate and differentiate into several cell lineages, and to migrate and home into the damaged tissues have made them attractive candidates for cell therapy and tissue engineering applications. Normal stem cell function is tied to the cell-intrinsic mechanisms and extrinsic signals derived from the surrounding microenvironment or circulation. Understanding the regulatory signals that govern stem cell functions is essential in order to have full knowledge about organogenesis, tissue maintenance and tissue plasticity in the physiological condition. It is also important for optimizing tissue engineering and improving the therapeutic efficiency of stem cells in regenerative medicine. A growing body of evidence indicates that hormonal signals can critically influence stem cell functions in fetal, postnatal, and adult tissues. This review focuses on recent studies revealing how growth hormone, insulin, thyroid hormone, parathormone, adrenocorticotropin, glucocorticoids, erythropoietin, and gastrointestinal hormones control stem cell behavior through influencing survival, proliferation, migration, homing, and differentiation of these cells. Moreover, how environmental factors such as exercise, hypoxia, and nutrition might affect stem cell functions through influencing the endocrine system is discussed. Some of the current limitations of cell therapy and how hormones can help overcoming these limitations are briefly outlined. PMID:26337380

  7. Stem Cells in Skin Wound Healing: Are We There Yet?

    PubMed Central

    Cerqueira, Mariana Teixeira; Pirraco, Rogério Pedro; Marques, Alexandra Pinto

    2016-01-01

    Significance: Cutaneous wound healing is a serious problem worldwide that affects patients with various wound types, resulting from burns, traumatic injuries, and diabetes. Despite the wide range of clinically available skin substitutes and the different therapeutic alternatives, delayed healing and scarring are often observed. Recent Advances: Stem cells have arisen as powerful tools to improve skin wound healing, due to features such as effective secretome, self-renewal, low immunogenicity, and differentiation capacity. They represent potentially readily available biological material that can particularly target distinct wound-healing phases. In this context, mesenchymal stem cells have been shown to promote cell migration, angiogenesis, and a possible regenerative rather than fibrotic microenvironment at the wound site, mainly through paracrine signaling with the surrounding cells/tissues. Critical Issues: Despite the current insights, there are still major hurdles to be overcome to achieve effective therapeutic effects. Limited engraftment and survival at the wound site are still major concerns, and alternative approaches to maximize stem cell potential are a major demand. Future Directions: This review emphasizes two main strategies that have been explored in this context. These comprise the exploration of hypoxic conditions to modulate stem cell secretome, and the use of adipose tissue stromal vascular fraction as a source of multiple cells, including stem cells and factors requiring minimal manipulation. Nonetheless, the attainment of these approaches to target successfully skin regeneration will be only evident after a significant number of in vivo works in relevant pre-clinical models. PMID:27076994

  8. Stem cell therapy – Hype or hope? A review

    PubMed Central

    Nadig, Roopa R

    2009-01-01

    While the regeneration of a lost tissue is known to mankind for several years, it is only in the recent past that research on regenerative medicine/dentistry has gained momentum and eluded the dramatic yet scientific advancements in the field of molecular biology. The growing understanding of biological concepts in the regeneration of oral/dental tissues coupled with experiments on stem cells is likely to result in a paradigm shift in the therapeutic armamentarium of dental and oral diseases culminating in an intense search for “biological solutions to biological problems.” Stem cells have been successfully isolated from variety of human tissues including orofacial tissues. Initial evidence from pioneering studies has documented the likely breakthrough that stem cells offer for various life-threatening diseases that have so far defeated modern medical care. The evidence gathered so far has propelled many elegant studies exploring the role of stem cells and their manifold dental applications. This review takes you on a sojourn of the origin of stem cells, their properties, characteristics, current research, and their potential applications. It also focuses on the various challenges and barriers that we have to surmount before translating laboratory results to successful clinical applications heralding the dawn of regenerative dentistry. PMID:20543921

  9. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging

    PubMed Central

    2013-01-01

    Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient’s own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging. PMID:23673056

  10. Myocardial regeneration potential of adipose tissue-derived stem cells

    SciTech Connect

    Bai, Xiaowen; Alt, Eckhard

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

  11. Stem Cell Therapy for Pediatric Dilated Cardiomyopathy

    PubMed Central

    Selem, Sarah M.; Kaushal, Sunjay; Hare, Joshua M.

    2014-01-01

    Dilated cardiomyopathy is a serious and life-threatening disorder in children. It is the most common form of pediatric cardiomyopathy. Therapy for this condition has varied little over the last several decades and mortality continues to be high. Currently, children with dilated cardiomyopathy are treated with pharmacological agents and mechanical support, but most require heart transplantation and survival rates are not optimal. The lack of common treatment guidelines and inadequate survival rates after transplantation necessitates more therapeutic clinical trials. Stem cell and cell-based therapies offer an innovative approach to restore cardiac structure and function towards normal, possibly reducing the need for aggressive therapies and cardiac transplantation. Mesenchymal stem cells and cardiac stem cells may be the most promising cell types for treating children with dilated cardiomyopathy. The medical community must begin a systematic investigation of the benefits of current and novel treatments such as stem cell therapies for treating pediatric dilated cardiomyopathy. PMID:23666883

  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. Analytical strategies for studying stem cell metabolism

    PubMed Central

    Arnold, James M.; Choi, William T.; Sreekumar, Arun

    2015-01-01

    Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology. PMID:26213533

  14. 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

    2009-03-01

    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

  15. 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

  16. 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

  17. Adult Stem Cells and Diseases of Aging.

    PubMed

    Boyette, Lisa B; Tuan, Rocky S

    2014-01-21

    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

  18. 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

  19. Time to Reconsider Stem Cell Induction Strategies

    PubMed Central

    Denker, Hans-Werner

    2012-01-01

    Recent developments in stem cell research suggest that it may be time to reconsider the current focus of stem cell induction strategies. During the previous five years, approximately, the induction of pluripotency in somatic cells, i.e., the generation of so-called ‘induced pluripotent stem cells’ (iPSCs), has become the focus of ongoing research in many stem cell laboratories, because this technology promises to overcome limitations (both technical and ethical) seen in the production and use of embryonic stem cells (ESCs). A rapidly increasing number of publications suggest, however, that it is now possible to choose instead other, alternative ways of generating stem and progenitor cells bypassing pluripotency. These new strategies may offer important advantages with respect to ethics, as well as to safety considerations. The present communication discusses why these strategies may provide possibilities for an escape from the dilemma presented by pluripotent stem cells (self-organization potential, cloning by tetraploid complementation, patenting problems and tumor formation risk). PMID:24710555

  20. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation

    PubMed Central

    Burrello, Jacopo; Monticone, Silvia; Gai, Chiara; Gomez, Yonathan; Kholia, Sharad; Camussi, Giovanni

    2016-01-01

    Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system. PMID:27597941

  1. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation.

    PubMed

    Burrello, Jacopo; Monticone, Silvia; Gai, Chiara; Gomez, Yonathan; Kholia, Sharad; Camussi, Giovanni

    2016-01-01

    Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system. PMID:27597941

  2. 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.

  3. Mesenchymal Stem Cells: New Players in Retinopathy Therapy

    PubMed Central

    Rajashekhar, Gangaraju

    2014-01-01

    Retinopathies in human and animal models have shown to occur through loss of pericytes resulting in edema formation, excessive immature retinal angiogenesis, and neuronal apoptosis eventually leading to blindness. In recent years, the concept of regenerating terminally differentiated organs with a cell-based therapy has evolved. The cells used in these approaches are diverse and include tissue-specific endogenous stem cells, endothelial progenitor (EPC), embryonic stem cells, induced pluripotent stem cells (iPSC) and mesenchymal stem cells (MSC). Recently, MSC derived from the stromal fraction of adipose tissue have been shown to possess pluripotent differentiation potential in vitro. These adipose stromal cells (ASC) have been differentiated in a number of laboratories to osteogenic, myogenic, vascular, and adipocytic cell phenotypes. In vivo, ASC have been shown to have functional and phenotypic overlap with pericytes lining microvessels in adipose tissues. Furthermore, these cells either in paracrine mode or physical proximity with endothelial cells, promoted angiogenesis, improved ischemia–reperfusion, protected from myocardial infarction, and were neuroprotective. Owing to the easy isolation procedure and abundant supply, fat-derived ASC are a more preferred source of autologous mesenchymal cells compared to bone marrow MSC. In this review, we present evidence that these readily available ASC from minimally invasive liposuction will facilitate translation of ASC research into patients with retinal diseases in the near future. PMID:24795699

  4. Cancer stem cells and differentiation therapy.

    PubMed

    Sell, Stewart

    2006-01-01

    Cancers arise from stem cells in adult tissues and the cells that make up a cancer reflect the same stem cell --> progeny --> differentiation progression observed in normal tissues. All adult tissues are made up of lineages of cells consisting of tissue stem cells and their progeny (transit-amplifying cells and terminally differentiated cells); the number of new cells produced in normal tissue lineages roughly equals the number of old cells that die. Cancers result from maturation arrest of this process, resulting in continued proliferation of cells and a failure to differentiate and die. The biological behavior, morphological appearance, and clinical course of a cancer depend on the stage of maturation at which the genetic lesion is activated. This review makes a comparison of cancer cells to embryonic stem cells and to adult tis sue stem cells while addressing two basic questions: (1) Where do cancers come from?, and (2) How do cancers grow? The answers to these questions are critical to the development of approaches to the detection, prevention, and treatment of cancer. PMID:16557043

  5. Targeting cancer stem cells using immunologic approaches

    PubMed Central

    Pan, Qin; Li, Qiao; Liu, Shuang; Ning, Ning; Zhang, Xiaolian; Xu, Yingxin; Chang, Alfred E.; Wicha, Max S.

    2015-01-01

    Cancer stem cells (CSCs) represent a small subset of tumor cells which have the ability to self-renew and generate the diverse cells that comprise the tumor bulk. They are responsible for local tumor recurrence and distant metastasis. However, they are resistant to conventional radiotherapy and chemotherapy. Novel immunotherapeutic strategies which specifically target CSCs may improve the efficacy of cancer therapy. To immunologically target CSC phenotypes, innate immune responses to CSCs have been reported using NK cells and γδT cells. To target CSC specifically, in vitro CSC-primed T cells have been successfully generated and shown targeting of CSCs in vivo after adoptive transfer. Recently, CSC-based dendritic cell vaccine has demonstrated significant induction of anti-CSC immunity both in vivo in immunocommpetent hosts and in vitro as evident by CSC reactivity of CSC vaccine-primed antibodies and T cells. In addition, identification of specific antigens or genetic alterations in CSCs may provide more specific targets for immunotherapy. ALDH, CD44, CD133 and HER2 have served as markers to isolate CSCs from a number of tumor types in animal models and human tumors. They might serve as useful targets for CSC immunotherapy. Finally, since CSCs are regulated by interactions with the CSC niche, these interactions may serve as additional targets for CSC immunotherapy. Targeting the tumor microenvironment, such as interrupting the immune cell e.g. myeloid derived suppressor cells, and cytokines e.g. IL-6 and IL-8, as well as the immune checkpoint (PD1/PDL1, et.al) may provide additional novel strategies to enhance the immunological targeting of CSCs. PMID:25873269

  6. Signaling in colon cancer stem cells.

    PubMed

    Roy, Sanchita; Majumdar, Adhip Pn

    2012-01-01

    : Colorectal cancer is the fourth most common form of cancer worldwide and ranks third among the cancer-related deaths in the US and other Western countries. It occurs with equal frequency in men and women, constituting 10% of new cancer cases in men and 11% in women. Despite recent advancement in therapeutics, the survival rates from metastatic are less than 5%. Growing evidence supports the contention that epithelial cancers including colorectal cancer, the incidence of which increases with aging, are diseases driven by the pluripotent, self-renewing cancer stem cells (CSCs). Dysregulation of Wnt, Notch, Hedgehog and/or TGF-β signaling pathways that are involved in proliferation and maintenance of CSCs leads to the development of CRC. This review focuses on the signaling pathways relevant for CRC to understand the mechanisms leading to tumor progression and therapy resistance, which may help in the development of therapeutic strategies for CRC. PMID:22866952

  7. Stem cell dynamics in the hair follicle niche

    PubMed Central

    Rompolas, Panteleimon; Greco, Valentina

    2014-01-01

    Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

  8. Molecular pathways in myocardial development: a stem cell perspective.

    PubMed

    Solloway, Mark J; Harvey, Richard P

    2003-05-01

    The heart has long been considered to adapt to increased work or pathology through the cellular growth process of hypertrophy. However, recent evidence for the existence of endogenous stem cells and regenerative capacity in the adult heart has given new impetus to the quest for cell therapies for heart failure, which remains the number one killer in Western cultures. The molecular cues driving cardiac development are now being explored in detail and will come into sharp focus as regimes for stem cell differentiation and efforts to augment endogenous regeneration are trialed. This review briefly outlines the current state of knowledge on the molecular basis of the four modalities of myogenesis that have been identified in the developing vertebrate heart. Stem cell-mediated myogenic repair in the heart represents a fifth modality, and an exciting frontier with basic and practical implications that remain to be explored. PMID:12757862

  9. VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells

    SciTech Connect

    Oka, Naoki; Soeda, Akio . E-mail: ccd29400@nyc.odn.ne.jp; Inagaki, Akihito; Onodera, Masafumi; Maruyama, Hidekazu; Hara, Akira; Kunisada, Takahiro; Mori, Hideki; Iwama, Toru

    2007-08-31

    There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche.

  10. From teratocarcinomas to embryonic stem cells.

    PubMed Central

    Andrews, Peter W

    2002-01-01

    The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so-called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem-cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential. PMID:12028783

  11. Cancer Stem Cell Plasticity Drives Therapeutic Resistance

    PubMed Central

    Doherty, Mary R.; Smigiel, Jacob M.; Junk, Damian J.; Jackson, Mark W.

    2016-01-01

    The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence. PMID:26742077

  12. Cancer Stem Cell Plasticity Drives Therapeutic Resistance.

    PubMed

    Doherty, Mary R; Smigiel, Jacob M; Junk, Damian J; Jackson, Mark W

    2016-01-01

    The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence. PMID:26742077

  13. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    SciTech Connect

    Neuzil, Jiri; E-mail: j.neuzil@griffith.edu.au; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

    2007-04-20

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133{sup +} cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well.

  14. Stem cell therapy in oral and maxillofacial region: An overview

    PubMed Central

    Sunil, PM; Manikandhan, R; Muthu, MS; Abraham, S

    2012-01-01

    Cells with unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects. PMID:22434942

  15. Virotherapy against malignant glioma stem cells.

    PubMed

    Dey, Mahua; Ulasov, Ilya V; Lesniak, Maciej S

    2010-03-01

    Glioblastoma multiforme, the most common primary intracranial malignancy, is associated with very poor outcome despite advances in surgical techniques and chemo- and radiation therapy. Many novel treatment modalities are being investigated with varying amount of success. Evolution of cancer stem cell hypothesis provides a new venue for developmental therapeutics. In this review, we highlight the literature regarding the existence of glioma stem cells and their characteristics. We also discuss the potential for virotherapy, a novel therapeutic approach utilizing conditionally replicative viruses, to directly target this population of self-renewing cancer stem cells. PMID:19643532

  16. Virotherapy Against Malignant Glioma Stem Cells

    PubMed Central

    Dey, Mahua; Ulasov, Ilya V.; Lesniak, Maciej S.

    2009-01-01

    Glioblastoma multiforme, the most common primary intracranial malignancy, is associated with very poor outcome despite advances in surgical techniques and chemo- and radiation therapy. Many novel treatment modalities are being investigated with varying amount of success. Evolution of cancer stem cell hypothesis provides a new venue for developmental therapeutics. In this review, we highlight the literature regarding the existence of glioma stem cells and their characteristics. We also discuss the potential for virotherapy, a novel therapeutic approach utilizing conditionally replicative viruses, to directly target this population of self-renewing cancer stem cells. PMID:19643532

  17. Isolation and Enrichment of Stem Cells

    NASA Astrophysics Data System (ADS)

    Bosio, Andreas; Huppert, Volker; Donath, Susan; Hennemann, Petra; Malchow, Michaela; Heinlein, Uwe A. O.

    Stem cells have the potential to revolutionize tissue regeneration and engineering. Both general types of stem cells, those with pluripotent differentiation potential as well as those with multipotent differentiation potential, are of equal interest. They are important tools to further understanding of general cellular processes, to refine industrial applications for drug target discovery and predictive toxicology, and to gain more insights into their potential for tissue regeneration. This chapter provides an overview of existing sorting technologies and protocols, outlines the phenotypic characteristics of a number of different stem cells, and summarizes their potential clinical applications.

  18. Autologous Stem Cell Mobilization and Collection.

    PubMed

    Hsu, Yen-Michael S; Cushing, Melissa M

    2016-06-01

    Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation. Developing hematopoietic stem/progenitor cell (HSPC) mobilization methods and collection algorithms have improved efficiency, clinical outcomes, and cost effectiveness. Differences in mobilization mechanisms may change the HSPC content harvested and result in different engraftment kinetics and complications. Patient-specific factors can affect mobilization. Incorporating these factors in collection algorithms and improving assays for evaluating mobilization further extend the ability to obtain sufficient HSPCs for hematopoietic repopulation. Technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects. PMID:27112997

  19. Endometrial regeneration and endometrial stem/progenitor cells.

    PubMed

    Gargett, Caroline E; Nguyen, Hong P T; Ye, Louie

    2012-12-01

    The functional layer of the human endometrium is a highly regenerative tissue undergoing monthly cycles of growth, differentiation and shedding during a woman's reproductive years. Fluctuating levels of circulating estrogen and progesterone orchestrate this dramatic remodeling of human endometrium. The thin inactive endometrium of postmenopausal women which resembles the permanent basal layer of cycling endometrium retains the capacity to respond to exogenous sex steroid hormones to regenerate into a thick functional endometrium capable of supporting pregnancy. Endometrial regeneration also follows parturition and endometrial resection. In non menstruating rodents, endometrial epithelium undergoes rounds of proliferation and apoptosis during estrus cycles. The recent identification of adult stem cells in both human and mouse endometrium suggests that epithelial progenitor cells and the mesenchymal stem/stromal cells have key roles in the cyclical regeneration of endometrial epithelium and stroma. This review will summarize the evidence for endometrial stem/progenitor cells, examine their role in mouse models of endometrial epithelial repair and estrogen-induced endometrial regeneration, and also describe the generation of endometrial-like epithelium from human embryonic stem cells. With markers now available for identifying endometrial mesenchymal stem/stromal cells, their possible role in gynecological diseases associated with abnormal endometrial proliferation and their potential application in cell-based therapies to regenerate reproductive and other tissues will be discussed. PMID:22847235

  20. Stem Cell Research and Health Education

    PubMed Central

    Eve, David J.; Marty, Phillip J.; McDermott, Robert J.; Klasko, Stephen K.; Sanberg, Paul R.

    2009-01-01

    Stem cells are being touted as the greatest discovery for the potential treatment of a myriad of diseases in the new millennium, but there is still much research to be done before it will be known whether they can live up to this description. There is also an ethical debate over the production of one of the most valuable types of stem cell: the embryonic form. Consequently, there is public confusion over the benefits currently being derived from the use of stem cells and what can potentially be expected from their use in the future. The health educator’s role is to give an unbiased account of the current state of stem cell research. This paper provides the groundwork by discussing the types of cells currently identified, their potential use, and some of the political and ethical pitfalls resulting from such use. PMID:19672471

  1. Bioprinting and Differentiation of Stem Cells.

    PubMed

    Irvine, Scott A; Venkatraman, Subbu S

    2016-01-01

    The 3D bioprinting of stem cells directly into scaffolds offers great potential for the development of regenerative therapies; in particular for the fabrication of organ and tissue substitutes. For this to be achieved; the lineage fate of bioprinted stem cell must be controllable. Bioprinting can be neutral; allowing culture conditions to trigger differentiation or alternatively; the technique can be designed to be stimulatory. Such factors as the particular bioprinting technique; bioink polymers; polymer cross-linking mechanism; bioink additives; and mechanical properties are considered. In addition; it is discussed that the stimulation of stem cell differentiation by bioprinting may lead to the remodeling and modification of the scaffold over time matching the concept of 4D bioprinting. The ability to tune bioprinting properties as an approach to fabricate stem cell bearing scaffolds and to also harness the benefits of the cells multipotency is of considerable relevance to the field of biomaterials and bioengineering. PMID:27617991

  2. The Androgen Receptor Bridges Stem Cell-Associated Signaling Nodes in Prostate Stem Cells

    PubMed Central

    Davies, Alastair H.; Zoubeidi, Amina

    2016-01-01

    The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self-renewal. Until recently, attention has focused almost exclusively on a small set of “core” transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR) in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells. PMID:26880966

  3. 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

  4. Human embryonic stem cells and lung regeneration

    PubMed Central

    Varanou, A; Page, C P; Minger, S L

    2008-01-01

    Human embryonic stem cells are pluripotent cells derived from the inner cell mass of preimplantation stage embryos. Their unique potential to give rise to all differentiated cell types has generated great interest in stem cell research and the potential that it may have in developmental biology, medicine and pharmacology. The main focus of stem cell research has been on cell therapy for pathological conditions with no current methods of treatment, such as neurodegenerative diseases, cardiac pathology, retinal dysfunction and lung and liver disease. The overall aim is to develop methods of application either of pure cell populations or of whole tissue parts to the diseased organ under investigation. In the field of pulmonary research, studies using human embryonic stem cells have succeeded in generating enriched cultures of type II pneumocytes in vitro. On account of their potential of indefinite proliferation in vitro, embryonic stem cells could be a source of an unlimited supply of cells available for transplantation and for use in gene therapy. Uncovering the ability to generate such cell types will expand our understanding of biological processes to such a degree that disease understanding and management could change dramatically. PMID:18724383

  5. A rare human syndrome provides genetic evidence that WNT signaling is required for reprogramming of fibroblasts to induced pluripotent stem cells

    PubMed Central

    Ross, Jason; Busch, Julia; Mintz, Ellen; Ng, Damian; Stanley, Alexandra; Brafman, David; Sutton, V. Reid; Van den Veyver, Ignatia; Willert, Karl

    2015-01-01

    SUMMARY WNT signaling promotes the reprogramming of somatic cells to an induced pluripotent state. We provide genetic evidence that WNT signaling is a requisite step during the induction of pluripotency. Fibroblasts from individuals with Focal Dermal Hypoplasia (FDH), a rare genetic syndrome caused by mutations in the essential WNT processing enzyme PORCN, fail to reprogram using standard methods. This blockade in reprogramming is overcome by ectopic WNT signaling and by PORCN overexpression, thus demonstrating that WNT signaling is essential for reprogramming. The rescue of reprogramming is critically dependent on the level of WNT signaling: steady baseline activation of the WNT pathway yields karyotypically normal iPS cells, whereas daily stimulation with Wnt3a produces FDH-iPS cells with severely abnormal karyotypes. Therefore, although WNT signaling is required for cellular reprogramming, inappropriate activation of WNT signaling induces chromosomal instability, highlighting the precarious nature of ectopic WNT activation, and its tight relationship with oncogenic transformation. PMID:25464842

  6. Clinical translation of human neural stem cells

    PubMed Central

    2013-01-01

    Human neural stem cell transplants have potential as therapeutic candidates to treat a vast number of disorders of the central nervous system (CNS). StemCells, Inc. has purified human neural stem cells and developed culture conditions for expansion and banking that preserve their unique biological properties. The biological activity of these human central nervous system stem cells (HuCNS-SC®) has been analyzed extensively in vitro and in vivo. When formulated for transplantation, the expanded and cryopreserved banked cells maintain their stem cell phenotype, self-renew and generate mature oligodendrocytes, neurons and astrocytes, cells normally found in the CNS. In this overview, the rationale and supporting data for pursuing neuroprotective strategies and clinical translation in the three components of the CNS (brain, spinal cord and eye) are described. A phase I trial for a rare myelin disorder and phase I/II trial for spinal cord injury are providing intriguing data relevant to the biological properties of neural stem cells, and the early clinical outcomes compel further development. PMID:23987648

  7. Clinical translation of human neural stem cells.

    PubMed

    Tsukamoto, Ann; Uchida, Nobuko; Capela, Alexandra; Gorba, Thorsten; Huhn, Stephen

    2013-01-01

    Human neural stem cell transplants have potential as therapeutic candidates to treat a vast number of disorders of the central nervous system (CNS). StemCells, Inc. has purified human neural stem cells and developed culture conditions for expansion and banking that preserve their unique biological properties. The biological activity of these human central nervous system stem cells (HuCNS-SC®) has been analyzed extensively in vitro and in vivo. When formulated for transplantation, the expanded and cryopreserved banked cells maintain their stem cell phenotype, self-renew and generate mature oligodendrocytes, neurons and astrocytes, cells normally found in the CNS. In this overview, the rationale and supporting data for pursuing neuroprotective strategies and clinical translation in the three components of the CNS (brain, spinal cord and eye) are described. A phase I trial for a rare myelin disorder and phase I/II trial for spinal cord injury are providing intriguing data relevant to the biological properties of neural stem cells, and the early clinical outcomes compel further development. PMID:23987648

  8. Analysis of glycosaminoglycans in stem cell glycomics.

    PubMed

    Li, Boyangzi; Liu, Haiying; Zhang, Zhenqing; Stansfield, Hope E; Dordick, Jonathan S; Linhardt, Robert J

    2011-01-01

    Glycosaminoglycans (GAGs) play a critical role in the binding and activation of growth factors in cell signal transduction required for biological development. A glycomics approach can be used to examine GAG content, composition, and structure in stem cells in order to characterize their general differentiation. Specifically, this method may be used to evaluate chondrogenic differentiations by profiling for the GAG content of the differentiated cells. Here, embryonic-like teratocarcinoma cells, NCCIT, a developmentally pluripotent cell line, were used as a model for establishing GAG glycomic methods, but will be easily transferrable to embryonic stem cell cultures. PMID:21043000

  9. Cancer stem cells in small cell lung cancer

    PubMed Central

    Verlicchi, Alberto; Rosell, Rafael

    2016-01-01

    Small cell lung cancer (SCLC) is one of the most aggressive lung tumors, with poor survival rates. Although patients may initially respond to treatment, this is followed by rapid development of drug resistance and disease progression. SCLC patients often present with metastasis at time of diagnosis, ruling out surgery as a treatment option. Currently, treatment options for this disease remain limited and platinum-based chemotherapy is the treatment of choice. A better understanding of the biology of SCLC could allow us to identify new therapeutic targets. Cancer stem cell (CSC) theory is currently crucial in cancer research and could provide a viable explanation for the heterogeneity, drug resistance, recurrence and metastasis of several types of tumors. Some characteristics of SCLC, such as aggressiveness, suggest that this kind of tumor could be enriched in CSCs, and drug resistance in SCLC could be attributable to the existence of a CSC subpopulation in SCLC. Herein we summarize current understanding of CSC in SCLC, including the evidence for CSC markers and signaling pathways involved in stemness. We also discuss potential ongoing strategies and areas of active research in SCLC, such as immunotherapy, that focus on inhibition of signaling pathways and targeting molecules driving stemness. Understanding of signaling pathways and the discovery of new therapeutic markers specific to CSCs will lead to new advances in therapy and improvements in prognosis of SCLC patients. Therefore, evaluation of these CSC-specific molecules and pathways may become a routine part of SCLC diagnosis and therapy. PMID:26958490

  10. Stem cells for heart valve regeneration.

    PubMed

    Weber, Benedikt; Emmert, Maximilian Y; Hoerstrup, Simon P

    2012-01-01

    Heart valve tissue engineering holds the potential to overcome limitations of currently used heart valve prostheses. It involves the isolation and expansion of autologous patient cells, the subsequent seeding of these cells onto an appropriate scaffold material, the in vitro incubation and the in vivo implantation of the derived tissue-engineered construct into the patient from whom the cells were taken. While vascular-derived cells require harvest of intact donor tissue and show limited expansion capacities, the use of stem or progenitor cells may overcome these limitations and expand the versatility of the concept of heart valve tissue engineering. Possible sources include cells isolated from blood, bone marrow, adipose tissue, amniotic fluid, chorionic villi, umbilical cord and induced pluripotent stem cells. Here we review different stem cell sources with particular regard to cellular phenotypes and their suitability for application in heart valve tissue engineering. PMID:22802212

  11. Engineering tissue from human embryonic stem cells

    PubMed Central

    Metallo, CM; Azarin, SM; Ji, L; De Pablo, JJ; Palecek, SP

    2008-01-01

    Abstract Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here, we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome. PMID:18194458

  12. Fat, Stem Cells, and Platelet-Rich Plasma.

    PubMed

    James, Isaac B; Coleman, Sydney R; Rubin, J Peter

    2016-07-01

    The ideal filler for aesthetic surgery is inexpensive and easy to obtain, natural in appearance and texture, immunologically compatible, and long lasting without risk of infection. By most metrics, autologous fat grafts meet these criteria perfectly. Although facial fat grafting is now a commonly accepted surgical procedure, there has been a wave of activity applying stem cells and platelet-rich plasma (PRP) therapies to aesthetic practice. This article addresses technical considerations in the use of autologous fat transfer for facial rejuvenation, and also explores the current evidence for these stem cell and PRP therapies in aesthetic practice. PMID:27363761

  13. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    PubMed

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function. PMID:26041660

  14. Hematopoietic stem cell enhancer: a powerful tool in stem cell biology.

    PubMed

    Koh, Cai Ping; Ng, Cherry Ee Lin; Nah, Giselle Sek Suan; Wang, Chelsia Qiuxia; Tergaonkar, Vinay; Matsumura, Takayoshi; Yokomizo, Tomomasa; Suda, Toshio; Osato, Motomi

    2015-06-01

    There has been considerable interest in identifying a cis-regulatory element that targets gene expression to stem cells. Such an element, termed stem cell enhancer, holds the promise of providing important insights into the transcriptional programs responsible for inherent stem cell-specific properties such as self-renewal capacity. The element also serves as a molecular handle for stem cell-specific marking, transgenesis and gene targeting, thereby becoming invaluable to stem cell research. A series of candidate enhancers have been identified for hematopoietic stem cells (HSCs). This review summarizes currently known HSC enhancers with emphasis on an intronic enhancer in the Runx1 gene which is essential for the generation and maintenance of HSCs. The element, named eR1 (+24m), is active specifically in HSCs, but not in progenitors, and is hence the most definitive HSC enhancer. PMID:25574754

  15. Stem cells used for cardiovascular tissue engineering.

    PubMed

    Siepe, Matthias; Akhyari, Payam; Lichtenberg, Artur; Schlensak, Christian; Beyersdorf, Friedhelm

    2008-08-01

    Stem cell research and tissue engineering have become leading fields in basic research worldwide. Especially in cardiovascular medicine, initial reports on the potential of using stem cells to recover cardiac function and replace organ subunits such as heart valves seemed to offer the promise of widespread clinical use in the near future. However, the broad application of this new therapy failed due to safety and efficacy concerns. Due in part to the initial reports, major basic research efforts were undertaken to explore the specific cell types in greater detail and identify their mechanisms of supporting function, resulting in remarkable new findings in stem cell biology. For example, the notion of resident human cardiac stem cells has disproved the earlier supposition that the human heart is a finitely differentiated organ without the intrinsic potential for regeneration. Furthermore, new technologies emerged to produce pluripotent cells without the ethical and immunological drawbacks of embryonic stem cells (for instance by nuclear transfer). Other autologous cell sources are presently under investigation in myocardial tissue engineering. For tissue engineering of heart valves and small calibre vessels, the use of autologous endothelial (precursor) cells may be the optimal means of seeding a biological or artificial scaffold. It is important that ongoing basic and clinical research in cardiovascular surgery might explore the potential of different cell types either using tissue engineering constructs or in cell transplantation approaches. PMID:18468449

  16. Cancer stem cell targeted therapy: progress amid controversies

    PubMed Central

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  17. 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". PMID:25171959

  18. Targeting cancer stem cells in solid tumors by vitamin D

    PubMed Central

    Jae Young, So; Nanjoo, Suh

    2014-01-01

    Cancer stem cells (CSCs) are a small subset of cells that may be responsible for initiation, progression and recurrence of tumors. Recent studies have demonstrated that CSCs are highly tumorigenic and resistant to conventional chemotherapies, making them a promising target for the development of preventive/therapeutic agents. A single or combination of various markers, such as CD44, EpCAM, CD49f, CD133, CXCR4, ALDH-1 and CD24, were utilized to isolate CSCs fromvarious types of human cancers. Notch, Hedgehog, Wnt, and TGF-β signalingregulate self-renewal and differentiation of normal stem cells andare aberrantly activated in CSCs. In addition, many studies have demonstrated that these stem cell-associated signaling pathways are required for the maintenance of CSCs in differentmalignancies, including breast, colorectal, prostate and pancreatic cancers. Accumulating evidence hasshowninhibitory effects of vitamin D and its analogs on the cancer stem cell signaling pathways, suggesting vitamin D as a potential preventive/therapeutic agent against CSCs.In this review, we summarize recent findings about the roles of Notch, Hedgehog, Wnt, and TGF-β signaling in CSCs as well as the effects of vitamin D on these stem cell signaling pathways. PMID:25460302

  19. Leukemia cell microvesicles promote survival in umbilical cord blood hematopoietic stem cells

    PubMed Central

    Razmkhah, Farnaz; Soleimani, Masoud; Mehrabani, Davood; Karimi, Mohammad Hossein; Kafi-abad, Sedigheh Amini

    2015-01-01

    Microvesicles can transfer their contents, proteins and RNA, to target cells and thereby transform them. This may induce apoptosis or survival depending on cell origin and the target cell. In this study, we investigate the effect of leukemic cell microvesicles on umbilical cord blood hematopoietic stem cells to seek evidence of apoptosis or cell survival. Microvesicles were isolated from both healthy donor bone marrow samples and Jurkat cells by ultra-centrifugation and were added to hematopoietic stem cells sorted from umbilical cord blood samples by magnetic associated cell sorting (MACS) technique. After 7 days, cell count, cell viability, flow cytometry analysis for hematopoietic stem cell markers and qPCR for P53 gene expression were performed. The results showed higher cell number, higher cell viability rate and lower P53 gene expression in leukemia group in comparison with normal and control groups. Also, CD34 expression as the most important hematopoietic stem cell marker, did not change during the treatment and lineage differentiation was not observed. In conclusion, this study showed anti-apoptotic effect of leukemia cell derived microvesicles on umbilical cord blood hematopoietic stem cells. PMID:26862318

  20. Stem cell platforms for regenerative medicine.

    PubMed

    Nelson, Timothy J; Behfar, Atta; Yamada, Satsuki; Martinez-Fernandez, Almudena; Terzic, Andre

    2009-06-01

    The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through strategies of replacement to implant functional tissues, regeneration to transplant progenitor cells or rejuvenation to activate endogenous self-repair mechanisms, the overarching goal of regenerative medicine is to translate stem cell platforms into practice and achieve cures for diseases limited to palliative interventions. Harnessing the full potential of each platform will optimize matching stem cell-based biologics with the disease-specific niche environment of individual patients to maximize the quality of long-term management, while minimizing the needs for adjunctive therapy. Emerging discovery science with feedback from clinical translation is therefore poised to transform medicine offering safe and effective stem cell biotherapeutics to enable personalized solutions for incurable diseases. PMID:19779576

  1. 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

  2. Mesenchymal stem cells in regenerative rehabilitation

    PubMed Central

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-01-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient’s medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID:27390452

  3. Mesenchymal stem cells in regenerative rehabilitation.

    PubMed

    Nurkovic, Jasmin; Dolicanin, Zana; Mustafic, Fahrudin; Mujanovic, Rifat; Memic, Mensur; Grbovic, Vesna; Skevin, Aleksandra Jurisic; Nurkovic, Selmina

    2016-06-01

    [Purpose] Regenerative medicine and rehabilitation contribute in many ways to a specific plan of care based on a patient's medical status. The intrinsic self-renewing, multipotent, regenerative, and immunosuppressive properties of mesenchymal stem cells offer great promise in the treatment of numerous autoimmune, degenerative, and graft-versus-host diseases, as well as tissue injuries. As such, mesenchymal stem cells represent a therapeutic fortune in regenerative medicine. The aim of this review is to discuss possibilities, limitations, and future clinical applications of mesenchymal stem cells. [Subjects and Methods] The authors have identified and discussed clinically and scientifically relevant articles from PubMed that have met the inclusion criteria. [Results] Direct treatment of muscle injuries, stroke, damaged peripheral nerves, and cartilage with mesenchymal stem cells has been demonstrated to be effective, with synergies seen between cellular and physical therapies. Over the past few years, several researchers, including us, have shown that there are certain limitations in the use of mesenchymal stem cells. Aging and spontaneous malignant transformation of mesenchymal stem cells significantly affect the functionality of these cells. [Conclusion] Definitive conclusions cannot be made by these studies because limited numbers of patients were included. Studies clarifying these results are expected in the near future. PMID:27390452

  4. Manipulation of pancreatic stem cells for cell replacement therapy.

    PubMed

    Peshavaria, M; Pang, K

    2000-01-01

    The demonstration of the existence of tissue-specific adult stem cells has had a great impact on our understanding of stem cell biology and its application in clinical medicine. Their existence has revolutionized the implications for the treatment of many degenerative diseases characterized by either the loss or malfunction of discrete cell types. However, successful exploitation of this opportunity requires that we have sufficient know-how of stem cell manipulation. Because stem cells are the founders of virtually all tissues during embryonic development, we believe that understanding the cellular and molecular mechanisms of embryogenesis and organogenesis will ultimately serve as a platform to identify factors and conditions that regulate stem cell behavior. Discovery of stem cell regulatory factors will create potential pharmaceutical opportunities for treatment of degenerative diseases, as well as providing critical knowledge of the processes by which stem cells can be expanded in vitro, differentiated, and matured into desired functional cells for implantation into humans. A well-characterized example of this is the hematopoietic system where the discovery of erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF), which regulate hematopoietic progenitor cell behavior, have provided significant clinical success in disease treatment as well as providing important insights into hematopoiesis. In contrast, little is known about the identity of pancreatic stem cells, the focus of this review. Recent reports of the potential existence of pancreatic stem cells and their utility in rescuing the diabetic state now raise the same possibilities of generating insulin-producing beta cells as well as other cell types of the pancreatic islet from a stem cell. In this review, we will focus on the potential of these new developments and how our understanding of pancreas development can help design strategies and approaches by which a cell replacement therapy

  5. De Novo Kidney Regeneration with Stem Cells

    PubMed Central

    Yokote, Shinya; Yamanaka, Shuichiro; Yokoo, Takashi

    2012-01-01

    Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration. PMID:23251079

  6. Embryonic and adult stem cell therapy.

    PubMed

    Brignier, Anne C; Gewirtz, Alan M

    2010-02-01

    There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID:20061008

  7. Heterochromatin components in germline stem cell maintenance

    PubMed Central

    Xing, Yalan; Li, Willis X.

    2015-01-01

    Stem cell maintenance requires expression of genes essential for stemness and repression of differentiation genes. How this is achieved remains incompletely understood. Here we investigate the requirement for central components of heterochromatin, Heterochromatin Protein 1 (HP1) and the histone H3 lys9 methyltransferase Su(var)3-9, in the Drosophila male germline stem cell (GSC) self-renewal, a paradigm for studying adult stem cell behavior. We found that mutations or RNAi knock down of HP1 or Su(var)3-9 cause loss of GSCs, accompanied by defects in cell division or survival and premature expression of the differentiation gene bag of marbles (bam). Conversely, over-expressing HP1 increases GSC number in wildtype flies and, strikingly, restores fertility to the sterile hopscotch (hop) mutant flies that lack niche signals. These results suggest that the central components of heterochromatin play roles including repressing differentiation genes in Drosophila male GSC maintenance. PMID:26626305

  8. Will embryonic stem cells change health policy?

    PubMed

    Sage, William M

    2010-01-01

    Embryonic stem cells are actively debated in political and public policy arenas. However, the connections between stem cell innovation and overall health care policy are seldom elucidated. As with many controversial aspects of medical care, the stem cell debate bridges to a variety of social conversations beyond abortion. Some issues, such as translational medicine, commercialization, patient and public safety, health care spending, physician practice, and access to insurance and health care services, are core health policy concerns. Other issues, such as economic development, technologic progress, fiscal politics, and tort reform, are only indirectly related to the health care system but are frequently seen through a health care lens. These connections will help determine whether the stem cell debate reaches a resolution, and what that resolution might be. PMID:20579256

  9. Hematopoietic stem cell engineering at a crossroads

    PubMed Central

    Rivière, Isabelle; Dunbar, Cynthia E.

    2012-01-01

    The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead. PMID:22096239

  10. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  11. Cell therapy using induced pluripotent stem cells or somatic stem cells: this is the question.

    PubMed

    Somoza, Rodrigo A; Rubio, Francisco J

    2012-05-01

    A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC). Whereas ES are primary involved in the genesis of new tissues and organs, SSC are involved in regeneration processes, immuno-regulatory and homeostasis mechanisms. Although the differentiating potential of ES is higher than SSC, several studies suggest that some types of SSC, such as mesenchymal stem cells (MSC), can be induced epigenetically to differentiate into tissue-specific cells of different lineages. This unexpected pluripotency and the variety of sources that they come from, can make MSC-like cells suitable for the treatment of diverse pathologies and injuries. New hopes for cell therapy came from somatic/mature cells and the discovery that could be reprogrammed to a pluripotent stage similar to ES, thus generating induced pluripotent stem cells (iPS). For this, it is necessary to overexpress four main reprogramming factors, Sox2, Oct4, Klf4 and c-Myc. The aim of this review is to analyze the potential and requirements of cellular based tools in human therapy strategies, focusing on the advantage of using MSC over iPS. PMID:22329581

  12. Perinatal stem cells: A promising cell resource for tissue engineering of craniofacial bone

    PubMed Central

    Si, Jia-Wen; Wang, Xu-Dong; Shen, Steve GF

    2015-01-01

    In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application. PMID:25621114

  13. Development in intracerebral stem cell grafts

    PubMed Central

    Reyes, Stephanny; Tajiri, Naoki; Borlongan, Cesar V.

    2015-01-01

    The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson’s disease, Huntington’s disease, stroke, and traumatic brain injury. PMID:25739415

  14. Engineering the CNS stem cell microenvironment

    PubMed Central

    Williams, Cicely A; Lavik, Erin B

    2010-01-01

    The loss of neural tissue underlies the symptomatology of several neurological insults of disparate etiology, including trauma, cerebrovascular insult and neurodegenerative disease. Restoration of damaged neural tissue through the use of exogenous or endogenous neural stem or progenitor cells is an enticing therapeutic option provided one can control their proliferation, migration and differentiation. Initial attempts at CNS tissue engineering relied on the intrinsic cellular properties of progenitor cells; however, it is now appreciated that the microenvironment surrounding the cells plays an indispensible role in regulating stem cell behavior. This article focuses on attempts to engineer the neural stem cell microenvironment by utilizing the major cellular components of the niche (endothelial cells, astrocytes and ependymal cells) and the extracellular matrix in which they are embedded. PMID:19903005

  15. Developments in intracerebral stem cell grafts.

    PubMed

    Reyes, Stephanny; Tajiri, Naoki; Borlongan, Cesar V

    2015-04-01

    The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson's disease, Huntington's disease, stroke and traumatic brain injury. PMID:25739415

  16. 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. PMID:26732838

  17. 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

  18. Stem cell factors in plants: chromatin connections.

    PubMed

    Kornet, N; Scheres, B

    2008-01-01

    The progression of pluripotent stem cells to differentiated cell lineages requires major shifts in cell differentiation programs. In both mammals and higher plants, this process appears to be controlled by a dedicated set of transcription factors, many of which are kingdom specific. These divergent transcription factors appear to operate, however, together with a shared suite of factors that affect the chromatin state. It is of major importance to investigate whether such shared global control mechanisms indicate a common mechanistic basis for preservation of the stem cell state, initiation of differentiation programs, and coordination of cell state transitions. PMID:19150963

  19. Entropy, Ergodicity, and Stem Cell Multipotency

    NASA Astrophysics Data System (ADS)

    Ridden, Sonya J.; Chang, Hannah H.; Zygalakis, Konstantinos C.; MacArthur, Ben D.

    2015-11-01

    Populations of mammalian stem cells commonly exhibit considerable cell-cell variability. However, the functional role of this diversity is unclear. Here, we analyze expression fluctuations of the stem cell surface marker Sca1 in mouse hematopoietic progenitor cells using a simple stochastic model and find that the observed dynamics naturally lie close to a critical state, thereby producing a diverse population that is able to respond rapidly to environmental changes. We propose an information-theoretic interpretation of these results that views cellular multipotency as an instance of maximum entropy statistical inference.

  20. 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. PMID:24928918

  1. [Glioma treatment strategies using mesenchymal stem cells].

    PubMed

    Namba, Hiroki

    2010-10-01

    Because of the growth characteristics of malignant gliomas that are highly invasive and deeply infiltrate the surrounding brain area; the surgical resection of these gliomas with preservation of neural functions is almost always noncurative. The residual tumor cells are usually resistant to standard adjuvant radiochemotherapy, and therefore, the tumors inevitably recur after a certain period and finally cause the death of the patients. Neural and mesenchymal stem cells have been extensively studied for the development of new strategies for treating malignant gliomas because of these cells possess the intrinsic property of homing toward tumor cells. By using neural and mesenchymal stem cells as vehicles for drug carriers, it is possible to deliver anticancer drugs to the tumor cells that infiltrate functioning normal brain tissue and are difficult to remove. Several cytokines and suicide genes have been tested, and promising results have been reported in animal brain tumor models. However, further studies involving safety issues such as secondary cancer formation are required before human trials of stem cell therapies. In the present paper, the author has reviewed the recent concepts involved in the treatment of malignant gliomas with stem cells, especially mesenchymal stem cells that are much easier to obtain from the patients themselves. PMID:20940507

  2. Perspectives on cancer stem cells in osteosarcoma.

    PubMed

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

    2013-09-10

    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

  3. Ewing's sarcoma cancer stem cell targeted therapy.

    PubMed

    Todorova, Roumiana

    2014-01-01

    Ewing`s sarcoma (ES) family of tumors (ESFTs) are round cell tumors of bone and soft tissues, afflicting children and young adults. This review summarizes the present findings about ES cancer stem cell (CSC) targeted therapy: prognostic factors, chromosomal translocations, initiation, epigenetic mechanisms, candidate cell of ES origin (Mesenchymal stem cells (MSCs) and Neural crest stem cells (NCSCs)). The ES CSC model, histopathogenesis, histogenesis, pathogenesis, ES mediated Hematopoietic stem progenitor cells (HSPCs) senescence are also discussed. ESFTs therapy is reviewed concerning CSCs, radiotherapy, risk of subsequent neoplasms, stem cell (SC) support, promising therapeutic targets for ES CSCs (CSC markers, immune targeting, RNAi phenotyping screens, proposed new drugs), candidate EWS-FLI1 target genes and further directions (including human embryonic stem cells (hESCs)). Bone marrow-derived human MSCs are permissive for EWS-FLI1 expression with transition to ESFT-like cellular phenotype. ESFTs are genetically related to NCSC, permissive for EWS-FLI1 expression and susceptible to oncogene-induced immortalization. Primitive neuroectodermal features and MSC origin of ESFTs provide a basis of immune targeting. The microRNAs profile of ES CSCs is shared by ESCs and CSCs from divergent tumor types. Successful reprogramming of differentiated human somatic cells into a pluripotent state allows creation of patient- and disease-specific SCs. The functional role of endogenous EWS at stem cell level on both senescence and tumorigenesis is a link between cancer and aging. The regulatory mechanisms of oncogenic activity of EWS fusions could provide new prognostic biomarkers, therapeutic opportunities and tumor-specific anticancer agents against ESFTs. PMID:24294922

  4. Limbal stem cell transplantation: current perspectives

    PubMed Central

    Atallah, Marwan Raymond; Palioura, Sotiria; Perez, Victor L; Amescua, Guillermo

    2016-01-01

    Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers

  5. Identification of Putative Fallopian Tube Stem Cells

    PubMed Central

    Snegovskikh, Victoria; Mutlu, Levent; Massasa, Effi

    2014-01-01

    Stem cells are used to repair and regenerate multiple tissues in the adult. We have previously shown that stem cells play a significant role in mediating endometrial repair and tissue regeneration. We hypothesized that the oviduct may possess a similar population of stem cells that contribute to the maintenance of this tissue. Here we identify label-retaining cells (LRCs) in the murine oviduct which indicate the presence of a stem/progenitor cell population in this tissue as well. Two-day-old CD-1 mice were injected intraperitoneally with 5-bromo-2-deoxyuridine (BrdU) or vehicle control. Female animals (n = 36 for each group) were killed at 6 weeks post injection. Reproductive tracts were removed, specimens were embedded in paraffin, and 5-µ sections were prepared. Oviduct was identified by hematoxylin and eosin staining and morphology. Immunofluorescence studies were performed on serial sections tissues (n = 12 per animal) using antibodies against BrdU. Confocal microscopy was used to identify 4′,6-diamidino-2-phenylindole (DAPI)- and BrdU-stained nuclei. In the group of mice exposed to BrdU, we identified a population of LRCs in all specimens and not in controls. The putative stem cells are located at the base of each villi, suggesting the location of the stem cell niche. The number of DAPI-stained nuclei divided by the number of LRCs; LRCs constituted 0.5% of all nucleated cells. The oviduct contains a population of progenitor cells, likely used in the repair and regeneration of fallopian tube. Defective or insufficient stem cell reserve may underlie common tubal diseases, including hydrosalpinx and ectopic pregnancy. PMID:25305130

  6. Current overview on dental stem cells applications in regenerative dentistry

    PubMed Central

    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. PMID:25810631

  7. Glucose-responsive insulin-producing cells from stem cells.

    PubMed

    Kaczorowski, David J; Patterson, Ethan S; Jastromb, William E; Shamblott, Michael J

    2002-01-01

    Recent success with immunosuppression following islet cell transplantation offers hope that a cell transplantation treatment for type 1 (juvenile) diabetes may be possible if sufficient quantities of safe and effective cells can be produced. For the treatment of type 1 diabetes, the two therapeutically essential functions are the ability to monitor blood glucose levels and the production of corresponding and sufficient levels of mature insulin to maintain glycemic control. Stem cells can replicate themselves and produce cells that take on more specialized functions. If a source of stem cells capable of yielding glucose-responsive insulin-producing (GRIP) cells can be identified, then transplantation-based treatment for type 1 diabetes may become widely available. Currently, stem cells from embryonic and adult sources are being investigated for their ability to proliferate and differentiate into cells with GRIP function. Human embryonic pluripotent stem cells, commonly referred to as embryonic stem (ES) cells and embryonic germ (EG) cells, have received significant attention owing to their broad capacity to differentiate and ability to proliferate well in culture. Their application to diabetes research is of particular promise, as it has been demonstrated that mouse ES cells are capable of producing cells able to normalize glucose levels of diabetic mice, and human ES cells can differentiate into cells capable of insulin production. Cells with GRIP function have also been derived from stem cells residing in adult organisms, here referred to as endogenous stem cell sources. Independent of source, stem cells capable of producing cells with GRIP function may provide a widely available cell transplantation treatment for type 1 diabetes. PMID:12469358

  8. Wnt/β-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells.

    PubMed

    Zhang, Zhaocheng; Nör, Felipe; Oh, Min; Cucco, Carolina; Shi, Songtao; Nör, Jacques E

    2016-06-01

    Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/β-catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, β-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/β-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587. PMID:26866635

  9. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    PubMed Central

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  10. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking.

    PubMed

    Ratajczak, M Z

    2015-04-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  11. Stem cell educator therapy and induction of immune balance.

    PubMed

    Zhao, Yong

    2012-10-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes the deficit of pancreatic islet β cells. A true cure has proven elusive despite intensive research pressure by using conventional approaches over the past 25 years. The situation highlights the challenges we face in conquering this disease. Alternative approaches are needed. Increasing evidence demonstrates that stem cells possess the function of immune modulation. We established the Stem Cell Educator therapy by using cord blood-derived multipotent stem cells (CB-SCs). A closed-loop system that circulates a patient's blood through a blood cell separator, briefly co-cultures the patient's lymphocytes with adherent CB-SCs in vitro, and returns the educated lymphocytes (but not the CB-SCs) to the patient's circulation. Our clinical trial reveals that a single treatment with the Stem Cell Educator provides lasting reversal of autoimmunity that allows regeneration of islet β cells and improvement of metabolic control in subjects with long-standing T1D. PMID:22833322

  12. Uterine stem cells--promise and possibilities.

    PubMed

    Pal, Lubna

    2015-11-01

    A fraction of cells residing in the uterine endometrium exhibit functional pluripotent potential, allowing them to be classified as adult stem cells. While the physiological relevance of this cell population is mostly conjectural at this juncture, uterine endometrial stem cells (UESC's) may underline pathogenesis of certain common gynecological disorders, such as endometriosis and adenomyosis. The ease of access and harvesting of UESC's and the diverse differentiation potential of this cell population has identified the uterine endometrium as a valuable source of autologous stem cells that can be harnessed through judicious application of principals of regenerative medicine. This mini review offers a glimpse into the journey, and an introduction to the spectrum of disorders that UESC's have the potential of impacting. PMID:26297687

  13. Vascular Potential of Human Pluripotent Stem Cells

    PubMed Central

    Iacobas, Ionela; Vats, Archana; Hirschi, Karen K.

    2010-01-01

    Cardiovascular disease is the number one cause of death and disability in the US. Understanding the biological activity of stem and progenitor cells, and their ability to contribute to the repair, regeneration and remodeling of the heart and blood vessels affected by pathologic processes is an essential part of the paradigm in enabling us to achieve a reduction in related deaths. Both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are promising sources of cells for clinical cardiovascular therapies. Additional in vitro studies are needed, however, to understand their relative phenotypes and molecular regulation toward cardiovascular cell fates. Further studies in translational animal models are also needed to gain insights into the potential and function of both human ES- and iPS-derived cardiovascular cells, and enable translation from experimental and pre-clinical studies to human trials. PMID:20453170

  14. Spheroid Culture of Mesenchymal Stem Cells

    PubMed Central

    Cesarz, Zoe; Tamama, Kenichi

    2016-01-01

    Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs) cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown. PMID:26649054

  15. The case for intrauterine stem cell transplantation.

    PubMed

    Mattar, Citra N; Biswas, Arijit; Choolani, Mahesh; Chan, Jerry K Y

    2012-10-01

    The clinical burden imposed by the collective group of monogenic disorders demands novel therapies that are effective at achieving phenotypic cure early in the disease process before the development of permanent organ damage. This is important for lethal diseases and also for non-perinatally lethal conditions that are characterised by severe disability with little prospect of postnatal cure. Where postnatal treatments are limited to palliative options, intrauterine stem-cell therapies may offer the potential to arrest pathogenesis in the early undamaged fetus. Intrauterine stem-cell transplantation has been attempted for a variety of diseases, but has only been successful in immune deficiency states in the presence of a competitive advantage for donor cells. This disappointing clinical record requires preclinical investigations into strategies that improve donor cell engraftment, including optimising the donor cell source and manipulating the microenvironment to facilitate homing. This chapter aims to outline the current challenges of intrauterine stem-cell therapy. PMID:22809469

  16. [Cancer stem cells: Radiotherapeutic features and therapeutic targets].

    PubMed

    Méry, Benoîte; Rancoule, Chloé; Guy, Jean-Baptiste; Espenel, Sophie; Wozny, Anne-Sophie; Simonet, Stéphanie; Vallard, Alexis; Alphonse, Gersende; Ardail, Dominique; Rodriguez-Lafrasse, Claire; Magné, Nicolas

    2016-01-01

    Recent evidences suggest that many types of cancers contain a cell population presenting stem cell properties. While the great majority of tumor cells are destined to differentiate, and eventually stop dividing, only a minority population of cells, termed cancer stem cells (CSCs), possesses extensive self-renewal capability and can recapitulate tumor pathophysiology in an immune-compromised animal model. Tumor initiating cells have been identified and isolated in many tumor types including brain, colon and prostate. They are virtually resistant to radiation and may contribute to treatment resistance and recurrence. Therefore, therapies specifically targeting CSCs will likely be needed for complete tumor eradication. The present study reviews published reports identifying the mechanisms of radioresistance of CSCs and potential targets based on the pathways of self-renewal. Further elucidation of pathways that regulate CSCs may provide insights into the development of novel innovative therapies. PMID:26702506

  17. Mesenchymal Stem Cells Migration Homing and Tracking

    PubMed Central

    Verfaillie, Catherine M.

    2013-01-01

    In this review, we discuss the migration and homing ability of mesenchymal stem cells (MSCs) and MSC-like cells and factors influencing this. We also discuss studies related to the mechanism of migration and homing and the approaches undertaken to enhance it. Finally, we describe the different methods available and frequently used to track and identify the injected cells in vivo. PMID:24194766

  18. Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury.

    PubMed

    Lee-Kubli, Corinne A; Lu, Paul

    2015-01-01

    The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell therapies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges. PMID:25788906

  19. Genome integrity, stem cells and hyaluronan

    PubMed Central

    Darzynkiewicz, Zbigniew; Balazs, Endre A.

    2012-01-01

    Faithful preservation of genome integrity is the critical mission of stem cells as well as of germ cells. Reviewed are the following mechanisms involved in protecting DNA in these cells: (a) The efflux machinery that can pump out variety of genotoxins in ATP-dependent manner; (b) the mechanisms maintaining minimal metabolic activity which reduces generation of reactive oxidants, by-products of aerobic respiration; (c) the role of hypoxic niche of stem cells providing a gradient of variable oxygen tension; (d) (e) the presence of hyaluronan (HA) and HA receptors on stem cells and in the niche; (f) the role of HA in protecting DNA from oxidative damage; (g) the specific function of HA in protecting DNA in stem cells; (h) the interactions of HA with sperm cells and oocytes that also may shield their DNA from oxidative damage, and (e) mechanisms by which HA exerts the anti-oxidant activity. While HA has multitude of functions its anti-oxidant capabilities are often overlooked but may be of significance in preservation of integrity of stem and germ cells genome. PMID:22383371

  20. Thrombosis in stem cell transplantation.

    PubMed

    Kansu, Emin

    2012-04-01

    Hemostatic changes and thrombotic events are frequent in patients undergoing stem cell transplantation. Arterial and venous thromboses are major causes of morbidity and mortality. Thrombotic complications can be classified into four groups including: catheter-related thrombosis, venous thromboembolic (VTE) events, sinusoidal obstructive syndrome (SOS)/veno-occlusive disease, and transplant-associated thrombotic microangiopathy (TAM). The incidence of catheter-related thrombosis is 8-20% in patients undergoing autologous hematopoietic stem cell transplantation (HSCT), and the incidence is low in syngeneic and allogeneic transplant patients. Venous duplex Doppler ultrasound, venogram, and computed tomography scan are required to visualize the venous thrombus. The treatment should be aimed at the prevention of pulmonary embolism, the avoidance of thrombus extension, and the preservation of catheter patency. Patients undergoing HSCT may have risk factors for VTE including underlying malignancy, traumatic brain injury, prolonged hospitalization, administration of conditioning regimens, and central venous catheters. Important risk factors are presence of history of VTE and graft-versus-host disease. One-year incidence of symptomatic VTE is 3.7%. SOS, also known as veno-occlusive disease, is a serious liver disease, seen in approximately 50-60% of HSCT patients. The mortality rate from the severe form of SOS is 84.3% and majority of the patients have multi-organ failure. The frequency is quite low after autologous transplantation. Risk factors for SOS include pre-existing hepatic damage, previous high-dose chemotherapy and abdominal irradiation, female gender and donor-recipient human leukocyte antigen disparity. Cyclophosphamide and busulphan are the most common agents with the highest incidence and fatal SOS. Histopathologic features of SOS include dilatation of sinusoids, necrosis of perivenular hepatocytes, and obstruction of small intrahepatic central venules by

  1. The regulation of hematopoietic stem cell populations

    PubMed Central

    Mayani, Hector

    2016-01-01

    Evidence presented over the last few years indicates that the hematopoietic stem cell (HSC) compartment comprises not just one but a number of different cell populations. Based on HSCs’ proliferation and engraftment potential, it has been suggested that there are two classes of HSC, with long- and short-term engraftment potential. HSC heterogeneity seems to involve differentiation capacities as well, since it has been shown that some HSC clones are able to give rise to both myeloid and lymphoid progeny, whereas others are lymphoid deficient. It has been recognized that HSC function depends on intrinsic cell regulators, which are modulated by external signals. Among the former, we can include transcription factors and non-coding RNAs as well as epigenetic modifiers. Among the latter, cytokines and extracellular matrix molecules have been implicated. Understanding the elements and mechanisms that regulate HSC populations is of significant relevance both in biological and in clinical terms, and research in this area still has to face several complex and exciting challenges. PMID:27408695

  2. Limbal stem cell failure secondary to advanced conjunctival squamous cell carcinoma: a clinicopathological case report

    PubMed Central

    Lyall, Douglas A M; Srinivasan, Sathish; Roberts, Fiona

    2009-01-01

    A 67-year-old man with a history of multiple myeloma (treated with chemotherapy) was referred with a left hyperaemic conjunctival lesion covering almost 360° of the limbus and extending onto the corneal surface. Conjunctival biopsy revealed conjunctival intraepithelial neoplasia. Initial treatment consisted of topical and intralesional injections of interferon α-2b. The patient subsequently developed limbal stem cell deficiency resulting in a persistent non-healing corneal epithelial defect. This was successfully managed with total excisional biopsy of the lesion, combined with limbal stem cell autograft (from the fellow eye) and amniotic membrane transplantation. Histopathology revealed a conjunctival squamous cell carcinoma. The corneal epithelium completely healed postoperatively and there is no evidence of tumour recurrence at 1 year follow-up. This case highlights a rare case of advanced ocular surface neoplasia causing secondary limbal stem cell deficiency. Medical and surgical management of ocular surface neoplasia with limbal stem cell transplantation is effective in treating such cases. PMID:22121391

  3. Melanoma Stem Cells and Metastasis: Mimicking Hematopoietic Cell Trafficking?

    PubMed Central

    Lee, Nayoung; Barthel, Steven R.; Schatton, Tobias

    2014-01-01

    Malignant melanoma is a highly metastatic cancer that bears responsibility for the majority of skin cancer-related deaths. Amidst the research efforts to better understand melanoma progression, there has been