ID: 82: DISTINCT ACTIONS OF ERα AND ERβ IN HUMAN PROSTATE STEM AND PROGENITOR CELL SELF-RENEWAL AND DIFFERENTIATION

2016 ◽  
Vol 64 (4) ◽  
pp. 928.1-928 ◽  
Author(s):  
D Hu ◽  
W Hu ◽  
S Majumdar ◽  
T Gauntner ◽  
Y Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Side Population ◽  
Population Analysis ◽  
Human Prostate ◽  
Mrna Levels ◽  
Self Renewal ◽  
Prostate Carcinogenesis ◽  
Prostate Epithelial Cells

Estrogens are implicated in prostate development and cancer, while stem cells are essential in tissue homeostasis and carcinogenesis. We have previously demonstrated that estradiol-17β (E2) treatment augments prostaspheres (PS) number and size, implicating them as direct estrogen targets. The present studies sought to elucidate specific roles for ERα and ERβ in prostate stem and progenitor cells.Prostate stem-progenitor cells were identified and isolated from normal primary prostate epithelial cells (PrEC) using long term BrdU retention in 3-D PS culture. FACS analyses (BrdU/ERα or ERβ) showed prostate stem and progenitor populations were both ERα+ and ERβ+. BrdU-retaining stem cells expressed high levels of ERβ and lower ERα as compared to non-label-retaining progenitor cells, suggesting ERβ dominance in the prostate stem cell. Estradiol increased BrdU-retaining cell numbers by enhancing stem cell self-renewal through symmetric division. While ERα siRNA blocked the E2-stimulated BrdU-retaining cells, ERβ knockdown augmented the E2-induced increase of BrdU-retaining cells. Together these findings suggest that ERα stimulates whereas ERβ suppresses stem cell self-renew. This conclusion is supported by separate studies on 2-D cultured PrEC with FACS stem-like cell side-population analysis using selective ER antagonists and siRNA. Although ERβ siRNA did not influence ERα mRNA levels, ERα siRNA doubled ERβ expression suggesting a suppressive role of ERα on ERβ action.In total, the present findings identify distinct localization patterns and roles for ERα and ERβ in human prostate stem-like and daughter progenitor cells with ERα driving self-renewal and ERβ braking division. We propose that a delicate balance between ERα and ERβ contributes to prostate stem cell niche homeostasis and that their dysregulation may contribute to prostate carcinogenesis and progression.

scholarly journals Actions of Estrogenic Endocrine Disrupting Chemicals on Human Prostate Stem/Progenitor Cells and Prostate Carcinogenesis

2016 ◽  
Vol 10 (1) ◽  
pp. 76-97 ◽  
Author(s):  
Dan-Ping Hu ◽  
Wen-Yang Hu ◽  
Lishi Xie ◽  
Ye Li ◽  
Lynn Birch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Endocrine Disrupting Chemicals ◽  
Human Prostate ◽  
Cancer Management ◽  
Prostate Carcinogenesis ◽  
Endocrine Disrupting ◽  
Cancer Initiation

Substantial evidences from epidemiological and animal-based studies indicate that early exposure to endocrine disrupting chemicals (EDCs) during the developmental stage results in a variety of disorders including cancer. Previous studies have demonstrated that early estrogen exposure results in life-long reprogramming of the prostate gland that leads to an increased incidence of prostatic lesions with aging. We have recently documented that bisphenol A (BPA), one of the most studied EDCs with estrogenic activity has similar effects in increasing prostate carcinogenic potential, supporting the connection between EDCs exposure and prostate cancer risk. It is well accepted that stem cells play a crucial role in development and cancer. Accumulating evidence suggest that stem cells are regulated by extrinsic factors and may be the potential target of hormonal carcinogenesis. Estrogenic EDCs which interfere with normal hormonal signaling may perturb prostate stem cell fate by directly reprogramming stem cells or breaking down the stem cell niche. Transformation of stem cells into cancer stem cells may underlie cancer initiation accounting for cancer recurrence, which becomes a critical therapeutic target of cancer management. We therefore propose that estrogenic EDCs may influence the development and progression of prostate cancer through reprogramming and transforming the prostate stem and early stage progenitor cells. In this review, we summarize our current studies and have updated recent advances highlighting estrogenic EDCs on prostate carcinogenesis by possible targeting prostate stem/progenitor cells. Using novel stem cell assays we have demonstrated that human prostate stem/progenitor cells express estrogen receptors (ER) and are directly modulated by estrogenic EDCs. Moreover, employing anin vivohumanized chimeric prostate model, we further demonstrated that estrogenic EDCs initiate and promote prostatic carcinogenesis in an androgen-supported environment. These findings support our hypothesis that prostate stem/progenitor cells may be the direct targets of estrogenic EDCs as a consequence of developmental exposure which carry permanent reprogrammed epigenetic and oncogenic events and subsequently deposit into cancer initiation and progression in adulthood.

scholarly journals Enhanced Immunological Tolerance by HLA-G1 from Neural Progenitor Cells (NPCs) Derived from Human Embryonic Stem Cells (hESCs)

2017 ◽  
Vol 44 (4) ◽  
pp. 1435-1444 ◽  
Author(s):  
Hong-Xi Zhao ◽  
Feng Jiang ◽  
Ya-Jing Zhu ◽  
Li Wang ◽  
Ke Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cells ◽  
Immune Tolerance ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Immunological Tolerance ◽  
Self Renewal ◽  
Hesc Lines

Background: Despite the great potential of utilizing human embryonic stem cells (hESCs)-derived cells as cell source for transplantation, these cells were often rejected during engraftment by the immune system due to adaptive immune response. Methods: We first evaluated HLA-G expression level in both hESCs and differentiated progenitor cells. After that, we generated modified hESC lines that over-express HLA-G1 using lentiviral infection with the construct contains both HLA-G1 and GFP tag. The lentivirus was first produced by co-transfecting HLA-G1 expressing lentiviral vector together with packaging vectors into packaging cell line 293T. Then the produced virus was used for the infection of selected hESC lines. We characterized the generated cell lines phenotype, including pluripotency and self-renewal abilities, as well as immune tolerance ability by mixed lymphocyte reaction (MLR) and cytotoxicity assays. Results: Although the hESCs do not express high levels of HLA-G1, over-expression of HLA-G1 in hESCs still retains their stem cell characteristics as determined by retaining the expression levels of OCT4 and SOX2, two critical transcriptional factors for stem cell function. Furthermore, the HLA-G1 overexpressing hESCs retain the self-renewal and pluripotency characteristics of stem cells, which can differentiate into different types of cells, including pigment cells, smooth muscle cells, epithelia-like cells, and NPCs. After differentiation, the differentiated cells including NPCs retain the high levels of HLA-G1 protein. In comparison with conventional NPCs, these HLA-G1 positive NPCs have enhanced immune tolerance ability. Conclusions: Ectopic expression of HLA-G1, a non-classical major histocompatibility complex class I (MHC I) antigen that was originally discovered involving in engraftment tolerance during pregnancy, can enhance the immunological tolerance in differentiated neural progenitor cells (NPCs). Our study shows that stably overexpressing HLA-G1 in hESCs might be a feasible strategy for enhancing the engraftment of NPCs during transplantation.

ID: 22: DIFFERENTIAL ACTIONS OF ESTROGEN RECEPTOR α AND β VIA NON-GENOMIC SIGNALING IN HUMAN PROSTATE STEM-PROGENITOR CELLS

2016 ◽  
Vol 64 (4) ◽  
pp. 933-933
Author(s):  
S Majumdar ◽  
JC Rinaldi ◽  
T Gauntner ◽  
L Xie ◽  
W Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Line ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Mapk Pathway ◽  
Human Prostate ◽  
Stem Cell Markers ◽  
Self Renewal ◽  
Progenitor Cell Proliferation

Genomic signaling via estrogen receptors (ER) has been widely studied and implicated as the main ER signaling pathway in prostate development and carcinogenesis. Non-genomic ER signaling has also been reported in prostate epithelium although down-stream cascades have not been clarified. Our lab has recently identified ERs in human prostate epithelial stem/progenitor cells and shown that that 17β-estradiol (E2) can stimulate stem cell symmetric self-renewal and progenitor cell proliferation. In this study we interrogate non-genomic membrane initiated ER signaling in this prostate stem/progenitor cell population. Human prostate stem-progenitor cells were enriched from primary prostate epithelial cell cultures (PrEC) of young, disease-free donors using a 3D prostasphere (PS) model as previously described. Cells were labeled using ERα or ERβ antibodies along with prostate stem cell markers CD49f and TROP2 followed by triple channel FACS to quantify ERα+/ERβ+ cell numbers. To explore ERα, the benign human prostate stem cell line WPE with extremely low levels of ERα and ERβ, was stably transfected with a lentiviral-ERα expression vector. The human prostate cancer stem-like cell line HuSLC (ERβ++, ERα−) was utilized to interrogate ERb actions. Cells were exposed to 10 nM estradiol (E2) over a 15 to 60 minute time course +/− ICI 182,870 (ICI), an ERα/β antagonist. FACS analysis of day 7 PS cells labeled for ERα or ERβ revealed 66% of day 7 PS cells as ERα+ and 40% as ERβ+. Among ERα or ERβ positive PS cells, 4% were Trop2+/CD49fhigh (stem-like cells) and 10–12% were Trop2+/CD49fmedium (early stage progenitor cells). PS exposed to 10 nM E2 showed sequential phosphorylation of Src, Erk1/2, p38, Akt and NFκB (p65) over 60 minutes. Phosphorylation of up-and downstream targets (EGFR, Jnk, GSK 3α/β, p70 S6 kinase, PRAS40, MSK1/2) was also seen using a phospho-kinase array. Furthermore, phosphorylation of ERα at S167 was noted over 60 min of E2 exposure enabling enhancement of genomic ERα transactivational activity in a feed-forward manner. ICI attenuated Akt and Erk1/2 phosphorylation, confirming membrane bound ERs are involved in downstream signaling. E2 treatment of HuSLCs showed phosphorylation of Erk1/2 but not Akt, indicating that ERβ signals exclusively through the MAPK pathway in these cells. Conversely, E2 treatment of WPE-stem cells overexpressing ERα resulted in robust phosphorylation of Akt but lower levels of Erk1/2 phosphorylation suggesting that Akt activation may be more reliant on ERα signaling. To identify pathway specific roles, specific inhibitors were added to PS cultures. PS treated with LY294002 (Akt inhibitor) for 7 days attenuated the E2-mediated increase in PS number and size. Inhibition of the NFκB downstream of the Akt pathway by IKK VII (IKK inhibitor) blocked p65 phosphorylation, abrogated the E2-induced increase in stem cell symmetric self-renewal and blunted E2 stimulation of progenitor cell proliferation. Analysis of PS cyclin mRNA levels revealed a G1 arrest of progenitor cells upon IKK inhibition suggesting an essential role of NFκB in progenitor cell amplification. MAPK pathway inhibition with U0126(Erk1/2 inhibitor) resulted in an attenuation of the E2-mediated increase in PS number and size and an increase stem cell symmetric self-renewal suggesting that MAPK pathway activation promotes commitment to stem and progenitor cell expansion. Taken together, the present findings reveal that human prostate stem-progenitor cells express both ERα and ERβ which differentially activate different signaling cascades originating at the membrane. These signaling events may lead to unique downstream actions that influence prostate stem-progenitor cell proliferation as well as lineage commitment decisions.

Gastrointestinal Stem Cells. III. Emergent themes of liver stem cell biology: niche, quiescence, self-renewal, and plasticity

2006 ◽  
Vol 290 (2) ◽  
pp. G189-G193 ◽  
Author(s):  
Neil D. Theise
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Biology ◽  
Stem Cell Niche ◽  
Progenitor Cell ◽  
Stem Cell Biology ◽  
Cell Plasticity ◽  
Self Renewal ◽  
Cell Niche

This essay will address areas of liver stem/progenitor cell studies in which consensus has emerged and in which controversy still prevails over consensus, but it will also highlight important themes that inevitably should be a focus of liver stem/progenitor cell investigations in coming years. Thus concepts regarding cell plasticity, the existence of a physiological/anatomic stem cell niche, and whether intrahepatic liver stem/progenitor cells comprise true stem cells or progenitor cells (or both) will be approached in some detail.

Identification of a Novel Candidate Regulator of HSC Aging.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1345-1345
Author(s):  
Erin J. Oakley ◽  
Gary Van Zant
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Secretory Pathway ◽  
Cell Function ◽  
Mammalian Species ◽  
Cell Aging ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Abstract It is well documented that both quantitative and qualitative changes in the murine hematopoietic stem cell (HSC) population occur with age. In mice, the effect of aging on stem cells is highly strain-specific, thus suggesting genetic regulation plays a role in HSC aging. We have previously mapped a quantitative trait locus (QTL) to murine Chr 2 that is associated with the variation in frequency of HSCs between aged B6 and D2 mice. In C57BL/6 (B6) mice the HSC population steadily increases with age, whereas in DBA/2 mice, this population declines. A QTL regulating the natural variation in lifespan between the two strains was mapped to the same location on mouse Chr 2, thus leading to the hypothesis that stem cell function affects longevity. B6 alleles, associated with expansion of the stem cell pool, are also associated with a ~50% increase in lifespan. Using a congenic mouse model, in which D2 alleles in the QTL interval were introgressed onto a B6 background, genome wide gene expression analyses were performed using sorted lineage negative hematopoietic cells, which are enriched for primitive stem and progenitor cells. Three variables were examined using Affymetrix M430 arrays:the effect of strain--congenic versus background;the effect of age--2 months versus 22 months; andthe effects of 2 Gy of radiation because previous studies indicated that congenic animals were highly sensitive to the effects of mild radiation compared to B6 background animals. Extensive analysis of the expression arrays pointed to a single strong candidate, the gene encoding ribosome binding protein 1 (Rrbp1). Real-time PCR was used to validate the differential expression of Rrbp1 in lineage negative, Sca-1+, c-kit+ (LSK) cells, a population highly enriched for stem and progenitor cells. Further analysis revealed the presence eight non-synonymous, coding single nucleotide polymorphisms (SNPs), and at least one of them because of its location and nature may significantly alter protein structure and function. The Rrbp1 gene consists of 23 exons in mouse and is highly conserved among mammalian species including mouse, human, and canine. The Rrbp1 protein is present on the surface of the rough endoplasmic reticulum where it tethers ribosomes to the membrane, stabilizes mRNA transcripts, and mediates translocation of nascent proteins destined for the cell secretory pathway. It is well established that the interaction of HSCs with microenvironmental niches in the bone marrow is crucial for their maintenance and self-renewal, and that this interaction is mediated in part by the molecular repertoires displayed on the cell surfaces of both HSCs and niche stromal cells. Therefore, we hypothesize that age and strain specific variation in Rrbp1, through its role in the secretory pathway, affects the molecular repertoire at the cell surface of the HSC, thus altering the way stem cells interact with their niches. This altered microenvironmental interaction could have profound effects on fundamental properties relevant to stem cell aging such as pluripotency, self-renewal, and senescence.

The Side Population Contains Functionally Distinct Hematopoietic Stem Cell Subpopulations

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2464-2464
Author(s):  
Grant Anthony Challen ◽  
Margaret A Goodell
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Side Population ◽  
Clonal Diversity ◽  
Stem Cell Markers ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Hematopoietic System

Abstract Over the decades since hematopoietic stem cells (HSCs) were first identified, the traditional view has been that the hematopoietic system is regenerated by a single pool of multipotent, quiescent HSCs that are sequentially recruited into cell cycle and which then progressively divide and differentiate until they are exhausted and ultimately replaced by the next cohort of stem cells. However, recent evidence has challenged this classical clonal succession model of HSC hierarchy by suggesting that the hematopoietic system is maintained by a pool of different HSC subtypes, with distinct self-renewal and differentiation potentials (the clonal diversity model, Figure 1). The side population (SP), characterized by Hoechst dye efflux, has been used as a method for isolating HSCs for over a decade and the SP has been shown to be highly enriched for HSC activity. While the entire SP is strikingly homogeneous with respect to expression of canonical stem cell markers such as Sca-1 and c-Kit, we recently observed heterogeneous expression for the SLAM family molecule CD150 within the SP, with CD150+ cells more prevalent in the lower SP and CD150− cell more prevalent in the upper SP. We decided to examine this observation further by investigating the properties of cells from different regions of the SP. Functional capacity was assessed by competitive bone marrow transplantation of upper SP cells, lower SP cells, and a combination of the two populations. Lower SP cells showed better engraftment than upper SP cells in recipient mice, a trend that continued when donor HSCs were isolated from primary recipients and re-transplanted into secondary hosts. Lower SP cells showed 3-fold better engraftment than upper SP cells in secondary transplants, suggesting better self-renewal capacity. However, analysis of the hematopoietic lineages formed by donor cells in recipient mice demonstrated that while both upper and lower SP cells were capable of forming all mature lineages, lower SP cells were biased towards myeloid differentiation while upper SP cells were biased towards lymphoid differentiation. The lineage biases observed from transplantation of one cell population alone were exacerbated when both upper and lower SP cells were co-transplanted into the same recipient mouse, suggesting that while both populations are capable of forming all hematopoietic lineages, in the presence of the other stem cell type (as would be the case in normal homeostasis) that the majority of the output from each HSC subtype is almost exclusively lymphoid or myeloid. The lineage contribution trends observed in the peripheral blood were also reproduced when bone marrow of transplanted mice was analyzed, including at the level of progenitors with lower SP cells showing greater ability to make myeloid progenitors (megakaryocyte-erythrocyte progenitors and granulocyte-macrophage progenitors) and upper SP cells producing proportionately more common lymphoid progenitors. Microarray analysis of upper and lower SP cells to determine the molecular signatures underlying these functional differences found many genes critical for long-term HSC self-renewal to be highly expressed in lower SP cells including Rb1, Meis1, Pbx1 and TGFbr2 while upper SP cells showed higher expression of cell cycle and activation genes. Cell cycle analysis showed upper SP cells to be approximately 2-fold more proliferative than lower SP cells (18.9% to 8.3% Ki-67+, 39.4% to 20.1% BrdU+ 3-days post-BrdU administration). The clonal diversity model which proposes the adult HSC compartment consists of a fixed number of different HSC subtypes each with pre-programmed behavior has important implications for using HSCs in experimental and clinical settings. While other studies have provided functional evidence for the clonal diversity model, this is the first study to prospectively isolate the functionally distinct HSC subtypes prior to transplantation. Figure Figure

Cellular and molecular basis of haematopoiesis

2020 ◽  
pp. 5172-5181
Author(s):  
Paresh Vyas ◽  
N. Asger Jakobsen
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Number ◽  
Stages Of Development ◽  
Self Renewal ◽  
Haematopoietic System

Haematopoiesis involves a regulated set of developmental stages from haematopoietic stem cells (HSCs) that produce haematopoietic progenitor cells that then differentiate into more mature haematopoietic lineages, which provide all the key functions of the haematopoietic system. Definitive HSCs first develop within the embryo in specialized regions of the dorsal aorta and umbilical arteries and then seed the fetal liver and bone marrow. At the single-cell level, HSCs have the ability to reconstitute and maintain a functional haematopoietic system over extended periods of time in vivo. They (1) have a self-renewing capacity during the life of an organism, or even after transplantation; (2) are multipotent, with the ability to make all types of blood cells; and (3) are relatively quiescent, with the ability to serve as a deep reserve of cells to replenish short-lived, rapidly proliferation progenitors. Haematopoietic progenitor cells are unable to maintain long-term haematopoiesis in vivo due to limited or absent self-renewal. Rapid proliferation and cytokine responsiveness enables increased blood cell production under conditions of stress. Lineage commitment means limited cell type production. The haematopoietic stem cell niche is an anatomically and functionally defined regulatory environment for stem cells modulates self-renewal, differentiation, and proliferative activity of stem cells, thereby regulating stem cell number. Haematopoietic reconstitution during bone marrow transplantation is mediated by a succession of cells at various stages of development. More mature cells contribute to repopulation immediately following transplantation. With time, cells at progressively earlier stages of development are involved, with the final stable repopulation being provided by long-lived, multipotent HSCs. Long-term haematopoiesis is sustained by a relatively small number of HSCs.

ID: 85: CROSS-TALK BETWEEN ESTROGEN RECEPTORS AND INSULIN-LIKE GROWTH FACTOR TYPE-1 RECEPTOR MODULATES HUMAN PROSTATE STEM/PROGENITOR CELL AMPLIFICATION

2016 ◽  
Vol 64 (4) ◽  
pp. 929.1-929 ◽  
Author(s):  
JD Rinaldi ◽  
W Hu ◽  
S Majundar ◽  
D Hu ◽  
GS Prins ◽  
...  
Keyword(s):  
Stem Cell ◽  
Estrogen Receptors ◽  
Signaling Pathways ◽  
Progenitor Cells ◽  
Cross Talk ◽  
Progenitor Cell ◽  
Human Prostate ◽  
Signal Molecules ◽  
Positive Interaction ◽  
Prostate Epithelial Cells

We previously demonstrated that estrogen regulates human prostate stem/progenitor cell amplification by directly targeting estrogen receptors (ERs); ERα stimulates whereas ERβ suppresses stem cell self-renewal. In addition to ERα and ERβ, we find that human prostate stem/progenitor cells express robust level of IGF-1R. Since ER actions can be modified by IGF-1R through ligand-independent ER phosphorylation, we herein sought to characterize potential cross-talk between estrogen and IGF-1 signaling pathways in regulating human prostate stem/progenitor cell amplification. Human prostate stem/progenitor cells were isolated from normal primary prostate epithelial cells (PrEC) using 3-D prostasphere (PS) culture. Similar to estradiol-17β (E2), 5 nM IGF-1 treatment increased the number of PS as well as long-term BrdU-retaining prostate stem cells. Conversely, knockdown of IGF-1R by siRNA decreased both parameters and consistently increased PS ERβ expression. Together these findings suggest that IGF-1R activation may drive prostate stem cell amplification through suppression of ERβ. Further studies revealed that E2 (10 nM) exposure induced IGF-1R phosphorylation while IGF-1R knockdown inhibited the non-genomic E2-induced pAkt and pERK confirming the cross-talk between these two signaling pathways. IGF-1R knockdown decreased PHLDA1, a known IGF-1 target gene, inhibited E2-induced ERα phosphorylation, suggesting a positive interaction between IGF-1R and ERα. In summary, the present results document robust crosstalk between estrogen and IGF-1 signaling which together regulate their downstream signal molecules including pAKT/pERK and PHLDA1. We propose that these pathways coordinately modulate prostate stem and progenitor cell numbers to effectively maintain glandular homeostasis. Supported by NIH/NCI award R01 CA172220; scholarship by FAPESP grant#2014/10965-6.

scholarly journals Stem Cell Repair for Cardiac Muscle Regeneration: A Review of the Literature

2016 ◽  
Vol 4 (1) ◽  
pp. 19-25
Author(s):  
Georgiana Farrugia ◽  
Rena Balzan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Side Population ◽  
Embryonic Stem ◽  
Cardiac Progenitor Cells ◽  
Cardiac Stem Cells ◽  
Skeletal Myoblasts ◽  
Islet 1

The notion that the human adult heart is a quiescent organ incapable of self-regeneration has been successfully challenged. It is now evident that the heart possesses a significant ability for repair and regeneration. Stem cells of endogenous cardiac origin are currently considered to possess the greatest ability to differentiate into cardiomyocytes. The major types of cardiac stem cells that show a promising potential to replace damaged cardiomyocytes include C-KIT positive (C-KIT+) cardiac progenitor cells, cardiosphere-derived progenitor cells, islet-1 (Isl1+) cardiac progenitor cells, side-population cardiac progenitor cells, epicardium-derived progenitor cells and stem cell antigen-1 (SCA1+) cardiac progenitor cells. Moreover, stem cells of extra-cardiac origin are also thought to restore contractility and vascularization of the myocardium. These include skeletal myoblasts, bone marrow mononuclear cells, mesenchymal stem cells, endothelial progenitor cells as well as embryonic stem cells. The need for further investigation on cardiac stem cell therapeutic strategies still remains.

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