scholarly journals Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote the Proliferation of Schwann Cells by Regulating the PI3K/AKT Signaling Pathway via Transferring miR-21

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yongbin Ma ◽  
Dan Zhou ◽  
Huanyan Zhang ◽  
Liming Tang ◽  
Fen Qian ◽  
...  

As an alternative mesenchymal stem cell- (MSC-) based therapy, MSC-derived extracellular vesicles (EVs) have shown promise in the field of regenerative medicine. We previously found that human umbilical cord mesenchymal stem cell-derived EVs (hUCMSC-EVs) improved functional recovery and nerve regeneration in a rat model of sciatic nerve transection. However, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that hUCMSC-EVs promoted the proliferation of Schwann cells by activating the PI3K/AKT signaling pathway. Furthermore, we showed that hUCMSC-EVs mediated Schwann cell proliferation via transfer of miR-21. Our findings highlight a novel mechanism of hUCMSC-EVs in treating peripheral nerve injury and suggest that hUCMSC-EVs may be an attractive option for clinical application in the treatment of peripheral nerve injury.

2021 ◽  
Vol 16 (11) ◽  
pp. 2170
Author(s):  
Yan-Bo Cheng ◽  
Chao Ren ◽  
De-Qin Geng ◽  
Rui-Cheng Zhang ◽  
Wen-Qi Du ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongli Li ◽  
Junxiu Zhang ◽  
Zijia Liu ◽  
Yuanyuan Gong ◽  
Zhi Zheng

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.


2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.


2011 ◽  
Vol 35 (3) ◽  
pp. 221-226 ◽  
Author(s):  
Chih Kong Tong ◽  
Shalini Vellasamy ◽  
Boon Chong Tan ◽  
Maha Abdullah ◽  
Sharmili Vidyadaran ◽  
...  

1998 ◽  
Vol 43 (2) ◽  
pp. 205-211 ◽  
Author(s):  
Jesper Sørensen ◽  
Georg Haase ◽  
Christian Krarup ◽  
Helene Gilgenkrantz ◽  
Axel Kahn ◽  
...  

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