Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

Simerman, Ariel A.; Phan, J.; Dumesic, Daniel A.; Chazenbalk, Gregorio D.

doi:10.1155/2016/1463258

Cited by 17 publications

(23 citation statements)

References 48 publications

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“…Recently, multilineage differentiating stress enduring (Muse) cells have been reported to be a novel population of nontumorigenic pluripotent stem cells [ 33 ]. They are able to differentiate into cells from all three embryonic germ layers both spontaneously and under media-specific induction.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

et al. 2017

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BackgroundWharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a novel and promising strategy for tissue engineering because of their ability to differentiate into many cell types. We characterized the differentiation of WJ-MSCs into endometrial epithelial cell (EEC)-like and endometrial stromal cell (ESC)-like cells and assessed the effect of 17β-estradiol and 8-Br-cAMP on the differentiation system.MethodsWJ-MSCs were treated in two ways to differentiate into EEC-like and ESC-like cells respectively: cocultured with ESCs in control/differentiation medium (17β-estradiol, growth factors); and cultured in control/differentiation medium (8-Br-cAMP alone or 8-Br-cAMP plus 17β-estrogen and growth factors). Three signaling pathway inhibitors (SB203580, PD98059, H89) were used to investigate the mechanism of WJ-MSC differentiation into ESC-like cells. Immunofluorescence, western blot and flow cytometry analyses were used to analyze expression of epithelial markers and stromal cell markers. Enzyme-linked immunosorbent assays were used to test the production of secretory proteins associated with the differentiation of ESC-like cells.Results17β-estradiol at 1 μM downregulated vimentin and CD13 and upregulated cytokeratin and CD9 proteins, promoting the differentiation of WJ-MSCs into EEC-like cells in the coculture system. 8-Br-cAMP at 0.5 mM upregulated vimentin and CD13 and downregulated CK and CD9, promoting the differentiation of WJ-MSCs into ESC-like cells. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) were upregulated and the protein kinase A (PKA) signaling pathway was activated, whereas extracellular signal-regulated (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were not affected.Conclusions17β-estradiol at 1 μM is a good inducer for facilitating the differentiation of WJ-MSCs into EEC-like cells. 8-Br-cAMP plus estrogen and growth factors can induce the differentiation of WJ-MSCs into ESC-like cells. During the differentiation of WJ-MSCs into ESC-like cells, PRL and IGFBP1 were upregulated by the treatment and the PKA signaling pathway was activated, whereas ERK1/2 and p38 MAPK were not affected. These findings suggest a promising approach to the treatment of endometrial damage and other endometrial diseases and suggest new applications for WJ-MSCs in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0700-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

et al. 2017

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“…There has also been a debate raised over the poor lineage-switching potential in MSCs and only a marginal population of MSCs was observed to successfully differentiate into the desired cell [ 82 ]. One possible explanation has been suggested on the presence of “rare cell” that occupies the residential MSCs niche, termed as multilineage-differentiating stress-enduring (MUSE) cells, in which they represent the subpopulation of successfully differentiated MSCs [ 82 , 83 ]. MUSE cells are pluripotent somatic stem cells that are found intimately tied to the fibroblasts or MSCs of all tissues or organs, while they intrinsically displayed phenotypic markers of ESCs, iPSCs, and MSCs, such as Stage-Specific Embryonic Antigen-3 (SSEA-3), Tumor Resistance Antigen 1-60 (TRA-1-60), Nanog, Oct3/4, and SOX2 [ 83 , 84 ].…”

Section: Mscs and Its Differentiation For The Treatment Of Retinalmentioning

confidence: 99%

“…One possible explanation has been suggested on the presence of “rare cell” that occupies the residential MSCs niche, termed as multilineage-differentiating stress-enduring (MUSE) cells, in which they represent the subpopulation of successfully differentiated MSCs [ 82 , 83 ]. MUSE cells are pluripotent somatic stem cells that are found intimately tied to the fibroblasts or MSCs of all tissues or organs, while they intrinsically displayed phenotypic markers of ESCs, iPSCs, and MSCs, such as Stage-Specific Embryonic Antigen-3 (SSEA-3), Tumor Resistance Antigen 1-60 (TRA-1-60), Nanog, Oct3/4, and SOX2 [ 83 , 84 ]. These cells displayed a comparable efficiency as ESCs in cell differentiation into multigerm lineages of mesodermal, endodermal, and ectodermal, and devoid of propensity into teratoma formation [ 83 ].…”

Section: Mscs and Its Differentiation For The Treatment Of Retinalmentioning

confidence: 99%

“…MUSE cells are pluripotent somatic stem cells that are found intimately tied to the fibroblasts or MSCs of all tissues or organs, while they intrinsically displayed phenotypic markers of ESCs, iPSCs, and MSCs, such as Stage-Specific Embryonic Antigen-3 (SSEA-3), Tumor Resistance Antigen 1-60 (TRA-1-60), Nanog, Oct3/4, and SOX2 [ 83 , 84 ]. These cells displayed a comparable efficiency as ESCs in cell differentiation into multigerm lineages of mesodermal, endodermal, and ectodermal, and devoid of propensity into teratoma formation [ 83 ]. Since, MUSE cells are generally present in scarce number, selective isolation and expansion of pure MUSE cell population would elevate the chances to direct differentiation into retinal neurons or RPE and further enhance the efficiency of stem cell-based therapy in various human ocular degenerative disorders.…”

Section: Mscs and Its Differentiation For The Treatment Of Retinalmentioning

confidence: 99%

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Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases

Ding

Kumar

Mok

2017

IJMS

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The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.

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“…Muse cells are distributed sporadically in connective tissue of nearly every organ and do not seem to associate with a structural niche [7]. Importantly, cells other than Muse cells that comprise MSCs do not express pluripotency genes, nor do they cross oligolineage boundaries such as between mesoderm, ectoderm and endoderm [6,7,16,17]. Adipose tissue Muse cells are well known to be resistant to multiple stress conditions, in culture they express embryonic markers such as Nanog, Oct¾, Nestin, Sox2, Pax6 and human pluripotent stem cell marker, stage-specific embryonic antigen-3 (ssea-3) [6,8,10].…”

mentioning

confidence: 99%

“Synapse-like” Connections between Adipocytes and Stem Cells: Morphological and Molecular Features of Human Adipose Tissue

Bertolotto¹,

Rosillo²,

Botti³

et al. 2018

J Stem Cell Dev Biol

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Adult mesenchymal stem cells are a heterogeneous population of stem cell that is not completely defined.The importance of increasing knowledge of this cell population will allow us to understand how to use them in multiple treatments for various diseases. Adipose tissue is a rich source from which to easily obtain a great amount of stem cells. We explore and study adipose stem cells (AdSCs) from human abdominal tissue by immunohistochemical analysis, transmission (TEM) and scanning (SEM) electron microscopy. The focus of this study is on the cell population that surrounds each adipocyte. In these populations of cells are included the adipose tissue stem cells (AdSCs) with different potentiality. We observe that the putative AdSCs have an intimate relationship involving close contact with adipocytes which we define here as "synapse-like." We show "synapse-like" connections between adipocytes and small cells to be mediated by connexin43 (Cx43). Our data suggest AdSCs constitute a heterogeneous population both in size and expression of different stem cell markers. We found that some of the AdSC attached to adipocytes are positive for Sox2, Pax6 and Nestin by immunostaining methods. TEM and SEM analysis demonstrate that small cells and adipocytes are surrounded by a compact mesh of collagen fibers that maintain physical adhesion between these cells. TEM also shows structural characteristics of putative stem cells and a presence of vesicles in synapse-like contact. SEM images moreover exhibited a large variation and quantity of cell sizes coexisting with adipocytes. Direct cell-to-cell communication could serve at least two purposes: a) as a survival strategy to maintain cells as stem cells, and b) as a source of signaling for differentiation into a new cell type.

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Muse Cells: Nontumorigenic Pluripotent Stem Cells Present in Adult Tissues—A Paradigm Shift in Tissue Regeneration and Evolution

Cited by 17 publications

References 48 publications

Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into endometrial cells

Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases

“Synapse-like” Connections between Adipocytes and Stem Cells: Morphological and Molecular Features of Human Adipose Tissue

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