Treatment of Osteochondral Femoral Head Defect by Human Umbilical Cord Mesenchymal Stem Cell Sheet Transplantation: An Experimental Study in Rats

Objective The study aimed to assess the feasibility of creating and transplanting human umbilical cord mesenchymal stem cell sheets applied to a rat model of hysterotomy, and additionally to determine benefits of human umbilical cord mesenchymal stem cell sheet transplantation in reducing uterine fibrosis and scarring. Study Design Human umbilical cord mesenchymal stem cell sheets are generated by culturing human umbilical cord mesenchymal stem cells on thermo-responsive cell culture plates. The temperature-sensitive property of these culture dishes facilitates normal cell culture in a thin contiguous layer and allows for reliable recovery of intact stem cell sheets without use of destructive proteolytic enzymes.We developed a rat hysterotomy model using nude rats. The rat uterus has two distinct horns: one horn provided a control/untreated scarring site, while the second horn was the cell sheet transplantation site.On day 14 following surgery, complete uteri were harvested and subjected to histologic evaluations of all hysterotomy sites. Results The stem cell sheet culture process yielded human umbilical cord mesenchymal stem cell sheets with surface area of approximately 1 cm2.Mean myometrial thickness in the cell sheet-transplanted group was 274 µm compared with 191 µm in the control group (p = 0.02). Mean fibrotic surface area in the human umbilical cord mesenchymal stem cell sheet-transplanted group was 95,861 µm2 compared with 129,185 µm2 in the control group. Compared with control horn sites, cell sheet-transplanted horns exhibited significantly smaller fibrotic-to-normal myometrium ratios (0.18 vs. 0.27, respectively, p = 0.029). Mean number of fibroblasts in cell sheet-transplanted horns was significantly smaller than the control horns (483 vs. 716/mm2, respectively, p = 0.001). Conclusion Human umbilical cord mesenchymal stem cell sheet transplantation is feasible in a rat model of hysterotomy. Furthermore, use of stem cell sheets reduces fibroblast infiltration and uterine scar fibrotic tissue formation during hysterotomy healing, potentially mitigating risks of uterine scar formation. Key Points

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Human Umbilical Cord Mesenchymal Stem Cell-Derived microRNA-30c-5p-Containing Extracellular Vesicles Alleviates Inflammatory Response of Diabetic Retinopathy Through Modulating the PLCG1/PKC/NF-κB Axis

SSRN Electronic Journal ◽

10.2139/ssrn.3514623 ◽

2020 ◽

Author(s):

Li Huang ◽

Jie Chen ◽

Xiaorong Gao ◽

Yujiao Dan ◽

Jinhua Gan ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Inflammatory Response ◽

Umbilical Cord ◽

Extracellular Vesicles ◽

Human Umbilical Cord

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Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02064-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Dongli Li ◽

Junxiu Zhang ◽

Zijia Liu ◽

Yuanyuan Gong ◽

Zhi Zheng

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Umbilical Cord ◽

Mechanism Of Action ◽

Epithelial Mesenchymal Transition ◽

Human Umbilical Cord ◽

Mesenchymal Transition ◽

Rpe Cells ◽

Subretinal Fibrosis

Abstract Background and aim Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo. Methods In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays. Results This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression. Conclusions The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.

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