Overexpression of tropomyosin receptor kinase A improves the survival and Schwann-like cell differentiation of bone marrow stromal cells in nerve grafts for bridging rat sciatic nerve defects

详细信息    查看全文

• 作者：Meige Zheng¹ ; ² ; ^* ; Junxiu Duan³ ; ^* ; Zhendan He³ ; Zhiwei Wang⁴ ; Shuhua Mu⁵ ; Zhiwen Zeng³ ; Junle Qu² ; Jian Zhang³ ; ^{jzhanghappy@163.com" class="auth_mail" title="E-mail the corresponding author} ; Dong Wang¹ ; ^{david74429@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BMSCs ; nerve transplantation ; Schwann-like cell differentiation ; shRNA interfere ; survival ; TrkA overexpression
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：18
• 期：10
• 页码：1256-1269
• 全文大小：2689 K

文摘

Bone marrow stromal cells (BMSCs) can differentiate into Schwann-like cells in vivo and effectively promote nerve regeneration and functional recovery as the seed cells for peripheral nerve repair. However, the survival rate and neural differentiation rate of the transplanted BMSCs are very low, which would limit their efficacy.

Methods

In this work, rat BMSCs were infected by recombinant lentiviruses to construct tropomyosin receptor kinase A (TrkA)-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then used in transplantation for rat sciatic nerve defects.

Results

We showed that lentivirus-mediated overexpression of TrkA in BMSCs can promote cell survival and protect against serum-starve-induced apoptosis in vitro. At 8 weeks after transplantation, the Schwann-like differentiated ratio of the existing implanted cells had reached 74.8 ± 1.6% in TrkA-overexpressing BMSCs-laden nerve grafts, while 40.7 ± 2.3% and 42.3 ± 1.5% in vector and control BMSCs-laden nerve grafts, but only 8.2 ± 1.8% in TrkA-shRNA-expressing BMSCs-laden nerve grafts. The cell apoptosis ratio of the existing implanted cells in TrkA-overexpressing BMSCs-laden nerve grafts was 16.5 ± 1.2%, while 33.9 ± 1.9% and 42.6 ± 2.9% in vector and control BMSCs-laden nerve grafts, but 87.2 ± 2.5% in TrkA-shRNA-expressing BMSCs-laden nerve grafts.

Conclusions

These results demonstrate that TrkA overexpression can improve the survival and Schwann-like cell differentiation of BMSCs and prevent cell death in nerve grafts, which may have potential implication in advancing cell transplantation for peripheral nerve repair.