Journal
CELL AND TISSUE BANKING
Volume 21, Issue 2, Pages 233-248Publisher
SPRINGER
DOI: 10.1007/s10561-020-09816-5
Keywords
Embryonic stem cells; Neural stem cells; Microvesicles; Sciatic nerve; Injury repair
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Funding
- Chinese Academy of Sciences
- National Natural Science Foundation of China [81571221]
- Natural Science Foundation of Jiangsu Province [BK20151346]
- Qing Lan Project of Jiangsu Province
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Injured nerves cannot regenerate on their own, and a lack of engraftable human nerves has been a major obstacle in cell-based therapies for regenerating damaged nerves. A monolayer culture approach to obtain adherent neural stem cells from human embryonic stem cells (hESC-NSCs) was established, and the greatest number of stemness characteristics were achieved by the eighth generation of hESC-NSCs (P8 hESC-NSCs). To overcome deficits in cell therapy, we used microvesicles secreted from P8 hESC-NSCs (hESC-NSC-MVs) instead of entire hESC-NSCs. To investigate the therapeutic efficacy of hESC-NSC-MVs in vitro, hESC-NSC-MVs were cocultured with dorsal root ganglia to determine the length of axons. In vivo, we transected the sciatic nerve in SD rats and created a 5-mm gap. A sciatic nerve defect was bridged using a silicone tube filled with hESC-NSC-MVs (45 mu g) in the MVs group, P8 hESC-NSCs (1 x 10(6) single cells) in the cell group and PBS in the control group. The hESC-NSC-MVs group showed better morphological recovery and a significantly greater number of regenerated axons than the hESC-NSCs group 12 weeks after nerve injury. These results indicated that the hESC-NSC-MVs group had the greatest ability to repair and reconstruct nerve structure and function. As a result, hESC-NSC-MVs may have potential for applications in the field of nerve regenerative repair.
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