Protective effect of human umbilical cord mesenchymal stem cell-derived exosomes on rat retinal neurons in hyperglycemia through the brain-derived neurotrophic factor/TrkB pathway

AIM: To explore whether human umbilical cord mesenchymal stem cell (hUCMSC)-derived exosomes (hUCMSC-Exos) protect rat retinal neurons in high-glucose (HG) conditions by activating the brain-derived neurotrophic factor (BDNF)-TrkB pathway. METHODS: hUCMSC-Exos were collected with differential ultracentrifugation methods and observed by transmission electron microscopy. Enzyme-linked immunosorbent assays (ELISAs) was used to quantify BDNF in hUCMSC-Exos, and Western blot was used to identify surface markers of hUCMSC-Exos. Rat retinal neurons were divided into 4 groups. Furthermore, cell viability, cell apoptosis, and TrkB protein expression were measured in retinal neurons. RESULTS: hUCMSCs and isolated hUCMSC-Exos were successfully cultured. All hUCMSC-Exos showed a diameter of 30 to 150 nm and had a phospholipid bimolecular membrane structure, as observed by transmission electron microscopy. ELISA showed the BDNF concentration of hUCMSCs-Exos was 2483.16±281.75. hUCMSCs-Exos effectively reduced the apoptosis of retinal neuron rate and improved neuron survival rate, meanwhile, the results of immunofluorescence verified the fluorescence intensity of TrKB in neurons increased. And all above effects were reduced by treated hUCMSCs-Exos with BDNF inhibitors. hUCMSC-Exos effectively reduced the apoptosis rate of retinal neurons by activating the BDNF-TrkB pathway in a HG environment. CONCLUSION: In the HG environment, hUCMSC-Exos could carry BDNF into rat retinal neurons, inhibiting neuronal apoptosis by activating the BDNF-TrkB pathway.

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Correlation of Scanning (SEM) and Transmission Electron Microscopy (TEM) of Human Umbilical Cord derived Mesenchymal Stromal Cells (hUC-MSCs)

Cytotherapy ◽

10.1016/j.jcyt.2020.03.193 ◽

2020 ◽

Vol 22 (5) ◽

pp. S107-S108

Author(s):

D. Tam ◽

Y. Leung ◽

W. Ng ◽

W. Lee ◽

F. Chan ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Umbilical Cord ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Umbilical Cord ◽

Transmission Electron

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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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