Effects of estrogen on growth and smooth muscle differentiation of vascular wall-resident CD34+ stem/progenitor cells

Wu, Yan; Shen, Yan; Kang, Kai; Zhang, Yanhong; Ao, Feng; Wan, Yu; Jiang, Song

doi:10.1016/j.atherosclerosis.2015.04.008

Cited by 12 publications

(8 citation statements)

References 39 publications

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“…The current study shows that exposure to E2 during the intermediate steps in the differentiation from hPSC to SMCs promotes gene expression of myogenic markers only in female hPSC-derived pSMCs. This is consistent with female animal data demonstrating that E2 treatment can promote the differentiation of female rat wall-resident CD34 + progenitor cells into vascular SMCs [50]. Our data also revealed that E2 treatment during the terminal differentiation step from pSMCs to SMCs did not affect gene expression of myogenic makers, suggesting that optimization of stem cell therapies for SMC with hormonal manipulation should be targeted at the intermediate stage of SMC differentiation.…”

Section: Discussionsupporting

confidence: 92%

“…It is interesting to note that while estrogen increased mitosis of male pSMCs, E2 treatment did not enhance the differentiation of male pSMCs from the VPC intermediate. Published data suggest that E2 can have different effects on CD34 + progenitor cells [50, 55]; it can accelerate the proliferation of undifferentiated CD34 + progenitor cells, while promoting further differentiation in differentiating progenitor cells. Thus, it is possible that there was a relatively higher fraction of undifferentiated VPCs that persisted in the male pSMC population compared to female pSMCs after FACS sorting.…”

Section: Discussionmentioning

confidence: 99%

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Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells

Wen

Green

et al. 2017

Stem Cell Res Ther

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BackgroundSmooth muscle progenitor cells (pSMCs) differentiated from human pluripotent stem cells (hPSCs) hold great promise for treating diseases or degenerative conditions involving smooth muscle pathologies. However, the therapeutic potential of pSMCs derived from men and women may be very different. Cell sex can exert a profound impact on the differentiation process of stem cells into somatic cells. In spite of advances in translation of stem cell technologies, the role of cell sex and the effect of sex hormones on the differentiation towards mesenchymal lineage pSMCs remain largely unexplored.MethodsUsing a standard differentiation protocol, two human embryonic stem cell lines (one male line and one female line) and three induced pluripotent stem cell lines (one male line and two female lines) were differentiated into pSMCs. We examined differences in the differentiation of male and female hPSCs into pSMCs, and investigated the effect of 17β-estradiol (E2) on the extracellular matrix (ECM) metabolisms and cell proliferation rates of the pSMCs. Statistical analyses were performed by using Student’s t test or two-way ANOVA, p < 0.05.ResultsMale and female hPSCs had similar differentiation efficiencies and generated morphologically comparable pSMCs under a standard differentiation protocol, but the derived pSMCs showed sex differences in expression of ECM proteins, such as MMP-2 and TIMP-1, and cell proliferation rates. E2 treatment induced the expression of myogenic gene markers and suppressed ECM degradation activities through reduction of MMP activity and increased expression of TIMP-1 in female pSMCs, but not in male pSMCs.ConclusionshPSC-derived pSMCs from different sexes show differential expression of ECM proteins and proliferation rates. Estrogen appears to promote maturation and ECM protein expression in female pSMCs, but not in male pSMCs. These data suggest that intrinsic cell-sex differences may influence progenitor cell biology.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0606-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells

Wen

Green

et al. 2017

Stem Cell Res Ther

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“…Previous research has demonstrated that E2 upregulated MHC-I and downregulated MHC-IIb expression in MDSCs [36]. Another study revealed that the ER/PI3K/Akt/SSH1L axis, but not MAPK signaling, is potentially responsible for the effects of estrogen on MSCs [37]. These findings suggest that the processes involve different mechanisms, which should be elucidated in further studies.…”

Section: Discussionmentioning

confidence: 90%

“…These conclusions are similar to the results of previous studies showing that E2 has dual effects on vascular wall-resident stem/progenitor cells. E2 was found to promote the proliferation of undifferentiated stem/progenitor cells by enhancing the binding of the pELK1-SRF complex to the c-Fos gene, whereas it accelerated the myogenic differentiation of differentiating stem/progenitor cells through an SRC3-mediated mechanism [37]. …”

Section: Discussionmentioning

confidence: 99%

Association of 17-β Estradiol with Adipose-Derived Stem Cells: New Strategy to Produce Functional Myogenic Differentiated Cells with a Nano-Scaffold for Tissue Engineering

Feng

Liu

et al. 2016

PLoS ONE

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The increased incidence of stress urinary incontinence (SUI) in postmenopausal women has been proposed to be associated with a reduction in the level of 17-β estradiol (E2). E2 has also been shown to enhance the multi-differentiation ability of adipose-derived stem cells (ASCs) in vitro. However, studies on the potential value of E2 for tissue engineering in SUI treatment are rare. In the present study, we successfully fabricated myogenically differentiated ASCs (MD-ASCs), which were seeded onto a Poly(l-lactide)/Poly(e-caprolactone) electrospinning nano-scaffold, and incorporated E2 into the system, with the aim of improving the proliferation and myogenic differentiation of ASCs. ASCs were collected from the inguinal subcutaneous fat of rats. The proliferation and myogenic differentiation of ASCs, as well as the nano-scaffold biocompatibility of MD-ASCs, with or without E2 supplementation, were investigated. We demonstrated that E2 incorporation enhanced the proliferation of ASCs in vitro, and the most optimal concentration was 10−9 M. E2 also led to modulation of the MD-ASCs phenotype toward a concentrated type with smooth muscle-inductive medium. The expression of early (alpha-smooth muscle actin), mid (calponin), and late-stage (myosin heavy chain) contractile markers in MD-ASCs was enhanced by E2 during the different differentiation stages. Furthermore, the nano-scaffold was biocompatible with MD-ASCs, and cell proliferation was significantly enhanced by E2. Taken together, these results demonstrate that E2 can enhance the proliferation and myogenic differentiation of ASCs and can be used to construct a biocompatible cell/nano-scaffold. These scaffolds with desirable differentiation cells show promising applications for tissue engineering.

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“…-154 - It has been widely reported that the SRF binding element (CArG) within the promoter region of SMC-specific genes is important not only for SMC gene regulation but also for SMC differentiation from vascular CD34 + stem/progenitor cells and normal stem/progenitor cells (Miano et al, 2004, Wu et al, 2015. Therefore, we asked whether the SRF element also plays a role in MECP2-mediated SMC gene…”

mentioning

confidence: 98%

Microrna-22 regulates smooth muscle cell differentiation from stem cells by targeting methyl cpg binding protein 2

Zhao

Huang

et al. 2014

Atherosclerosis

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Effects of estrogen on growth and smooth muscle differentiation of vascular wall-resident CD34+ stem/progenitor cells

Cited by 12 publications

References 39 publications

Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells

Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells

Association of 17-β Estradiol with Adipose-Derived Stem Cells: New Strategy to Produce Functional Myogenic Differentiated Cells with a Nano-Scaffold for Tissue Engineering

Microrna-22 regulates smooth muscle cell differentiation from stem cells by targeting methyl cpg binding protein 2

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