Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential

Mo, Miaohua; Wang, Shan; Zhou, Ying; Li, Hong; Wu, Yaojiong

doi:10.1007/s00018-016-2229-7

Cited by 105 publications

(83 citation statements)

References 121 publications

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“…MSCs could be isolated from many adult tissues and fetal appendages without too much ethical controversy and have been widely used to repair or regenerate damaged tissues and treat immune diseases in clinical trials also due to their multi-lineage differentiation potential and immunomodulatory function 7, 23 . MSCs derived from different tissues may have varied functional properties in spite of the similar morphologic characteristics and immunophenotypes, which make it complicated and confusing about what a source of MSCs to choose for a certain clinical purpose 15, 17 .…”

Section: Discussionmentioning

confidence: 99%

miR-301b~miR-130b—PPARγ axis underlies the adipogenic capacity of mesenchymal stem cells with different tissue origins

Liu

Chen

et al. 2017

Sci Rep

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Mesenchymal stem cells (MSCs) have been widely used in regenerative medicine and cellular therapy due to their multi-lineage differentiation potential and immunomodulatory function. The applicability of MSCs also depends on their cellular sources and in vivo functions. Here in this study, we systematically compared the morphologic characteristics, immunophenotypes and the adipogenic differentiation of MSCs derived from umbilical cord (UC), adipose tissue (Ad) and bone marrow (BM). We found that the three tissues-derived MSCs displayed decreased adipogenic capacity in the order: Ad-MSC > BM-MSC > UC-MSC, and no morphologic and immunophenotypic differences were observed. Mechanistic investigation revealed a miR-301b~miR-130b—PPARγ axis, whose expression pattern in UC-MSC, Ad-MSC and BM-MSC significantly correlates with their adipogenic capacity. Our results come up with a potential mechanism to elucidate the differential adipogenesis of Ad-MSC, BM-MSC and UC-MSC, which would provide instructional advice for which source of MSCs to choose according to a certain clinical purpose. Furthermore, the miR-301b~miR-130b—PPARγ axis may also be used as a potential therapeutic target for the disorders associated with MSCs-mediated abnormal adipogenesis.

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Section: Discussionmentioning

confidence: 99%

miR-301b~miR-130b—PPARγ axis underlies the adipogenic capacity of mesenchymal stem cells with different tissue origins

Liu

Chen

et al. 2017

Sci Rep

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“…The ultimate fate of multipotent mesenchymal stem cells first located in bone marrow are potentially adipogenic, osteogenic, and even myogenic (Mo et al, 2016), and contain highly functional leptin receptors (Hess et al, 2005). HDL, traditionally inversely linked to adipose tissue and BMI, is also shown to correlate with non-adipose components of the body such as skeletal mass (Pietrobelli et al, 1999.).…”

Section: Discussionmentioning

confidence: 99%

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Mosher¹,

Melton²,

Stapleton³

et al. 2016

Human Biology

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DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA which are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process.Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative function includes regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism and Pre-print version. Visit http://digitalcommons.wayne.edu/humbiol/ after publication to acquire the final version.reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examines the significance of variation in DNA methylation patterns along the leptin core promoter in four populations and uses biomarkers reflecting leptin's functional process in two of those populations to investigate the relevance of the ethnic variation identified in the DNA methylation. Those two populations are the Western Buryats of Siberia and the Mennonites of Central Kansas.LEP's core promoter region contains both the C/EBPα transcription binding site (TBS) which tempers the final step in adipocyte maturity and capacity to synthesize leptin and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, with others suggesting tissue-specific methylation variation at this region. We hypothesize that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers which reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system and anthropometric measures.A distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter is documented in all ethnicities and both sexes in our combined analyses of 313 individuals. This pattern replicates those identified in previous studies, thus suggesting a conserved core promoter region across populations. The second analyses in two of the four ...

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“…There is heterogeneity in the differentiation potential of MSC [20, 21], and there is heterogeneity in the expression of cell surface markers such as STRO-1 and CD271, and STRO-1 and CD271 expressing MSC have been demonstrated to possess enhanced immunomodulatory capacity [22, 23]. The heterogeneity of MSC may impair their therapeutic efficacy and introduce variations between studies [24].…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue-Derived Mesenchymal Stem Cells Have a Heterogenic Cytokine Secretion Profile

Hoogduijn

Baan

et al. 2017

Stem Cells International

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Mesenchymal stem cells derived from adipose tissue (ASC) have immune regulatory function, which makes them interesting candidates for cellular therapy. ASC cultures are however heterogeneous in phenotype. It is unclear whether all ASC contribute equally to immunomodulatory processes. ASC are also responsive to cytokine stimulation, which may affect the ratio between more and less potent ASC populations. In the present study, we determined IL-6 receptor (CD126 and CD130 subunits) and IFN-γ receptor (CD119) expression on ASC by flow cytometry. The production of IL-6 and IFN-γ was measured by ELISA and the frequency of IL-6 and IFN-γ secreting cells by ELISPOT. The results showed that ASC did not express CD126, and only 10–20% of ASC expressed CD130 on their surface, whereas 18–31% of ASC expressed CD119. ASC produced high levels of IL-6 and 100% of ASC were capable of secreting IL-6. Stimulation by IFN-γ or TGF-β had no effect on IL-6 secretion by ASC. IFN-γ was produced by only 1.4% of ASC, and TGF-β significantly increased the frequency to 2.7%. These results demonstrate that ASC cultures are heterogeneous in their cytokine secretion and receptor expression profiles. This knowledge can be employed for selection of potent, cytokine-producing, or responsive ASC subsets for cellular immunotherapy.

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Mesenchymal stem cell subpopulations: phenotype, property and therapeutic potential

Cited by 105 publications

References 121 publications

miR-301b~miR-130b—PPARγ axis underlies the adipogenic capacity of mesenchymal stem cells with different tissue origins

miR-301b~miR-130b—PPARγ axis underlies the adipogenic capacity of mesenchymal stem cells with different tissue origins

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Adipose Tissue-Derived Mesenchymal Stem Cells Have a Heterogenic Cytokine Secretion Profile

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