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Cell Tissue Bank. 2020 Feb 12. doi: 10.1007/s10561-020-09816-5. [Epub ahead of print]

Regeneration of sciatic nerves by transplanted microvesicles of human neural stem cells derived from embryonic stem cells.

Author information

1
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Jingkou District, Zhenjiang City, 212013, Jiangsu Province, China.
2
Department of Clinical Laboratory, Nantong First People's Hospital, Nantong, 226000, Jiangsu, China.
3
Department of Clinical Laboratory, Zhenjiang Centre for Disease Prevention and Control, Zhenjiang, 212003, Jiangsu, China.
4
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Jingkou District, Zhenjiang City, 212013, Jiangsu Province, China. hu@ujs.edu.cn.

Abstract

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 μg) in the MVs group, P8 hESC-NSCs (1 × 106 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.

KEYWORDS:

Embryonic stem cells; Injury repair; Microvesicles; Neural stem cells; Sciatic nerve

PMID:
32052220
DOI:
10.1007/s10561-020-09816-5

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