Therapeutic effect of human umbilical cord-derived mesenchymal stem cells on injured rat endometrium during its chronic phase

Zhang, Lu; Liu, Ying; Guan, Chun-Yi; Shen, Tian; Lv, Xiaodan; Li, Jianhui; Ma, Xu; Xia, Hong-Fei

doi:10.1186/s13287-018-0777-5

Cited by 154 publications

(119 citation statements)

References 38 publications

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“…It has been proven in several studies that ADSC improve the vasculature growth and new vessel formation either by differentiation into endothelial cells or by secreting vascular endothelial growth factor (VEGF) [ 31 , 42 , 58 ]. In our crush injury model we did not observe ADSC differentiation into endothelial cells; however, based on the recent published data showing the MSC-mediated vasculature repair of the damaged tissues correlating with increased VEGF levels, we cannot exclude the hypothesis that implanted ADSC support in-vivo muscle regeneration by proangiogenic factor secretion [ 59 – 61 ]. However, this hypothesis needs to be further verified.…”

Section: Discussionmentioning

confidence: 87%

Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation

et al. 2018

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BackgroundSkeletal muscle has a remarkable regenerative capacity. However, extensive damage that exceeds the self-regenerative ability of the muscle can lead to irreversible fibrosis, scarring, and significant loss of function. Adipose-derived stem cells (ADSC) are a highly abundant source of progenitor cells that have been previously reported to support the regeneration of various muscle tissues, including striated muscles. The aim of this study was to evaluate the effect of ADSC transplantation on functional skeletal muscle regeneration in an acute injury model.MethodsMouse ADSC were isolated from subcutaneous fat tissue and transplanted with a collagen hydrogel into the crushed tibialis anterior muscle of mice. Recovering muscles were analyzed for gene and protein expression by real-time quantitative polymerase chain reaction and immunohistochemistry. The muscle contractility was assessed by myography in an organ bath system.ResultsIntramuscular transplantation of ADSC into crushed tibialis anterior muscle leads to an improved muscle regeneration with ADSC residing in the damaged area. We did not observe ADSC differentiation into new muscle fibers or endothelial cells. However, the ADSC-injected muscles had improved contractility in comparison with the collagen-injected controls 28 days post-transplantation. Additionally, an increase in fiber cross-sectional size and in the number of mature fibers with centralized nuclei was observed.ConclusionsADSC transplantation into acute damaged skeletal muscle significantly improves functional muscle tissue regeneration without direct participation in muscle fiber formation. Cellular therapy with ADSC represents a novel approach to promote skeletal muscle regeneration.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0922-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 87%

Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation

et al. 2018

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“…Accordingly, the fertility testing demonstrated that embryo implantation efficiency is significantly higher in BMSCs group and VEGF-BMSCs group compared with the control group. The study has confirmed that UC-MSCs can promote endometrial proliferation and recover the endometrial embryo implantation ability [ 44 ]. This is consistent with our findings.…”

Section: Discussionmentioning

confidence: 82%

Therapeutic Effects of VEGF Gene-Transfected BMSCs Transplantation on Thin Endometrium in the Rat Model

Zhao

Yan

Huang

et al. 2018

Stem Cells International

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Objective Bone mesenchymal stem cells (BMSCs) transplantation has a therapeutic effect on the thin endometrium in animal researches and clinical trials. The present study aims at assessing whether transplantation of VEGF-transfected BMSCs (VEGF-BMSCs) have a better therapeutic effect on endometrial regeneration and endometrial receptivity compared with BMSCs therapy alone. Methods Sprague-Dawley (SD) rats were used in the study. Thin endometrium model was established with 95% ethanol injection into uterine. VEGF-BMSCs or BMSCs was transplanted via tail vein IV injection. Endometrial thickness, morphology, and pinopodes were assessed by hematoxylin and eosin (HE) staining and scanning electron microscope (SEM). The proteins and mRNAs expressions of markers for endometrial cells and endometrial receptivity were measured after treatment. The fertility testing was done to assess the embryo implantation efficiency. Results VEGF-BMSCs transplantation significantly increased endometrial thickness compared with the BMSCs group and the control group. There was no significant difference in endometrial thickness between VEGF-BMSCs group and sham operation group. Importantly, in protein level, expressions of cytokeratin, vitamin, VEGF, LIF, and integrin ανβ 3 in VEGF-BMSC group were increased dramatically compared with those of the control group and BMSC group both 4 days and 8 days after stem cells transplantation. Accordingly, mRNA expression of LIF and integrin α ν β 3 was significantly upregulated compared with those of the control group and BMSC group both 4 and 8 days after treatment. The pinopodes were developed better in the VEGF-BMSCs group and the sham operation group compared with BMSCs group and the control group. The number of embryo implantation is largest in the sham operation group, followed by VEGF-BMSCs group, BMSCs group, and the control group. Conclusions Transplantation of VEGF gene-transfected BMSCs may be a better therapeutic treatment for thin endometrium than stem cell therapy alone.

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“…In the past few years, the endometrial therapeutic effects of MSCs derived from different tissues such as bone marrow [17] , umbilical cord [18,19] , human decidual [20] , and uterus [21] have been investigated intensively, thus, providing new approaches to restore the endometrium to its normal morphology and function. In particular, the umbilical cord Wharton's jelly was reported to be an ideal source of stem cells for clinical treatment and scienti c research applications because of its highest concentration of allogeneic MSCs compared to that of other tissues [22] .…”

Section: Discussionmentioning

confidence: 99%

Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis

Shi

Sun

Wang

et al. 2020

Preprint

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Background Accumulating evidence indicates that mesenchymal stem cells (MSCs) exert tissue repair effects and therapeutic angiogenesis through their noncoding RNAs (ncRNAs). Our previous studies showed that MSCs derived from Wharton’s jelly (WJ-MSCs) can ameliorate damaged human endometrium by promoting angiogenesis. There is limited information on the functions and mechanism of ncRNAs in MSC-induced endometrial repair, and additional studies are needed for more insights.Methods Here, WJ-MSCs were cocultured with or without endometrial stromal cells (ESCs) damaged by mifepristone (cocultured group versus non-cocultured group). TUNEL staining assays, EdU proliferation assays, flow cytometry apoptosis assays, and western blot assays were performed to observe the reparative effect of WJ-MSCs on damaged ESCs. Subsequently, circular RNA (circRNA) and microRNA microarrays were performed between the two groups. A subset of top upregulated circRNAs was validated by qRT-PCR. The functions of circ6401 (hsa_circ_0006401) in WJ-MSCs were investigated using lentivirus-mediated circRNA overexpression assays. The subcellular localization of circ6401 and miR-29b-1-5p in WJ-MSCs was identified by double RNA fluorescence in situ hybridization. Dual-luciferase reporter assays and western blot assays were performed to elucidate the regulatory mechanisms among circ6401, miR-29b-1-5p, and RAP1B.Results WJ-MSCs significantly improved ESC proliferation and upregulated the expression of vascular angiogenesis markers. Circ6401 was upregulated in WJ-MSCs cocultured with damaged ESCs, while miR-29b-1-5p was significantly downregulated. Furthermore, circ6401 was found to bind to miR-29b-1-5p and prevent it from decreasing the level of RAP1B, a crucial protein involved in the VEGF signaling pathway, which promoted angiogenesis and stimulated the proliferation of ESCs.Conclusions Our results showed the abundance and regulation profiles of ncRNAs of WJ-MSCs during repair of damaged ESCs, and for the first time, clarified the underlying mechanism by which circ6401 promotes endometrial repair by WJ-MSCs; thus, demonstrating that circ6401 may serve as a potential therapeutic target.

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Therapeutic effect of human umbilical cord-derived mesenchymal stem cells on injured rat endometrium during its chronic phase

Cited by 154 publications

References 38 publications

Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation

Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation

Therapeutic Effects of VEGF Gene-Transfected BMSCs Transplantation on Thin Endometrium in the Rat Model

Circ6401, a novel circular RNA, is implicated in repair of the damaged endometrium by Wharton’s jelly-derived mesenchymal stem cells through regulation of the miR-29b-1-5p/RAP1B axis

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