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

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.

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Acknowledgments

We appreciate the stem cell bank of the Chinese Academy of Sciences under a Materials Transfer Agreement for providing us hESC lines (SHhES2). This work was supported by the National Natural Science Foundation of China (Grant No. 81571221), Natural Science Foundation of Jiangsu Province (Grant No. BK20151346) and Qing Lan Project of Jiangsu Province.

Author information

JH designed the research study, and XC and KY performed the research. JY and HW created the animal model. JH, XS and HX supplied study materials, instrumentation tools, computing resources, and other analysis tools. JG, LZ, XJ, TC, YD and BT analyzed the data. XC and KY wrote the article.

Correspondence to Jiabo Hu.

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Conflicts of interest

The authors declare that there are no competing interests.

Ethical approval

All experimental procedures were conducted in accordance with Chinese legislation on animal protection and were approved by the Ethics Committee of Jiangsu University.

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Rats walked freely in the PBS group (MP4 755 kb)

Rats walked freely in the hESC-NSCs group (MP4 1254 kb)

Rats walked freely in the hESC-NSC-MVs group (MP4 1331 kb)

Online Resource 1

Rats walked freely in the PBS group (MP4 755 kb)

Online Resource 2

Rats walked freely in the hESC-NSCs group (MP4 1254 kb)

Online Resource 3

Rats walked freely in the hESC-NSC-MVs group (MP4 1331 kb)

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Chen, X., Ye, K., Yu, J. et al. Regeneration of sciatic nerves by transplanted microvesicles of human neural stem cells derived from embryonic stem cells. Cell Tissue Bank (2020). https://doi.org/10.1007/s10561-020-09816-5

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Keywords

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