Nicotine-enhanced stemness and epithelial-mesenchymal transition of human umbilical cord mesenchymal stem cells promote tumor formation and growth in nude mice

Abstract Background and aimSubretinal 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 cells-derived exosomes have been reported to play a crucial part 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 hucMSC-Exo.Methods In this study, we successfully cultured and identified human umbilical cord-derived mesenchymal stem cells (hucMSC), and isolated exosomes from their supernatant by ultracentrifugation.Laser-induced (choroidal neovascularization) CNV and subretinal fibrosis model indicated that intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, we found that hucMSC-Exo could efficaciously suppress RPE cells migration and promote the mesenchymal–epithelial transition (MET) by delivering miR-27b-3p. Analysis of the latent binding of miR-27b-3p to HOXC6 was made by bioinformatics prediction and luciferase reporter assays. ResultsThe study showed that intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via suppression of EMT process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by the TGF-β2 via inhibiting HOXC6 (Homeobox protein Hox-C6) expression. ConclusionsThis study provided novel insights into the anti-fibrotic mechanism of hucMSC-Exo on subretinal fibrosis. HucMSCs-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, which indicated that exosomal miR-27b/HOXC6 axis could play a vital role on ameliorating subretinal fibrosis. Our study put forward a promising therapeutic agent for the treatment of ocular fibrotic diseases, as well as comprehension into the mechanism of hucMSC-Exo under subretinal fibrosis.

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Bone Regeneration by Nanohydroxyapatite/Chitosan/Poly(lactide-co-glycolide) Scaffolds Seeded with Human Umbilical Cord Mesenchymal Stem Cells in the Calvarial Defects of the Nude Mice

BioMed Research International ◽

10.1155/2015/261938 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Fei Wang ◽

Xiao-Xia Su ◽

Yu-Cheng Guo ◽

Ang Li ◽

Yin-Cheng Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Umbilical Cord ◽

Nude Mice ◽

Fluorescence Labeling ◽

Control Group ◽

Human Umbilical Cord ◽

Calvarial Defects

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs)in vitroand subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n=18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p<0.01). On the basis of previous studiesin vitroand in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.

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Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

Tissue Engineering Part A ◽

10.1089/ten.tea.2012.0047 ◽

2013 ◽

Vol 19 (5-6) ◽

pp. 685-696 ◽

Cited By ~ 27

Author(s):

Jee Hyun An ◽

Hyojung Park ◽

Jung Ah Song ◽

Kyung Ho Ki ◽

Jae-Yeon Yang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Loss ◽

Cord Blood ◽

Conditioned Medium ◽

Umbilical Cord ◽

Nude Mice ◽

Umbilical Cord Blood ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord

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The Therapeutic Effects of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells on Scleroderma

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-021-00405-5 ◽

2021 ◽

Author(s):

Yue Yu ◽

Liangliang Shen ◽

Xiaoyun Xie ◽

Jingjun Zhao ◽

Miao Jiang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Macrophage Polarization ◽

Enzyme Linked Immunosorbent Assay ◽

M2 Macrophage ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Mesenchymal Transition ◽

M1 Macrophage

Abstract Background: Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma. Methods: Mice with scleroderma received a single 50 μg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot. Results: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages. Conclusion: We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycin-induced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.

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