Combinatory transplantation of mesenchymal stem cells with flavonoid small molecule in acellular nerve graft promotes sciatic nerve regeneration.
Combinatory transplantation of mesenchymal stem cells with flavonoid small molecule in acellular nerve graft promotes sciatic nerve regeneration.
复制标题
间充质干细胞与类黄酮小分子联合移植到无细胞神经移植物中可促进坐骨神经再生。
DOI：
10.1177/2041731420980136
复制
发表时间：
2020-01
影响因子：
8.2
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Li WY;Jia H;Wang ZD;Zhai FG;Sun GD;Ma D;Liu GB;Li CM;Wang Y
先前的动物研究已经证明类黄酮小分子TrkB激动剂，7，8-二羟基黄酮（DHF），促进横断的外周神经中的轴突再生。在本研究中，我们研究了7，8-DHF治疗和骨髓源性干/基质细胞（BMSCs）植入脱细胞同种异体神经移植物（ANA）的联合作用，并探讨可能涉及的相关机制。我们的结果表明，与阴性对照组相比，TrkB和下游ERK 1/2磷酸化在7，8-DHF处理后增加。此外，7，8-DHF促进BMSCs的增殖、存活和Schwann样细胞分化。选择性ERK 1/2抑制剂U0126可抑制7，8-DHF诱导的ERK 1/2磷酸化上调，并部分抑制7，8-DHF诱导的细胞增殖、存活和Schwann样细胞分化。在体内，7，8-DHF促进移植的BMSCs的存活，并上调再生的ANA中的轴突生长和髓鞘形成。7，8-DHF + BMSCs还可提高靶肌肉组织的运动终板密度。这些益处与运动功能恢复的增加有关。7，8-DHF + BMSC显着上调再生ANA中TrkB和ERK1/2磷酸化表达，并增加腰脊髓中TrkB的表达。7，8-DHF的作用机制可能与其上调TrkB信号通路，激活再生ANA和脊髓中的下游生存信号分子ERK 1/2，提高移植BMSCs的存活率有关。该研究提供了新的基础数据，将7，8-DHF治疗在神经损伤和修复中的益处与BMSC生物学和功能联系起来，并证明了通过神经移植物移植治疗受损周围神经的潜在组合方法。
Previous animal studies have demonstrated that the flavonoid small-molecule TrkB agonist, 7, 8-dihydroxyflavone (DHF), promotes axon regeneration in transected peripheral nerves. In the present study, we investigated the combined effects of 7, 8-DHF treatment and bone marrow-derived stem/stromal cells (BMSCs) engraftment into acellular nerve allografts (ANAs) and explore relevant mechanisms that may be involved. Our results show that TrkB and downstream ERK1/2 phosphorylation are increased upon 7, 8-DHF treatment compared to the negative control group. Also, 7, 8-DHF promotes proliferation, survival, and Schwann-like cell differentiation of BMSCs in vitro. While selective ERK1/2 inhibitor U0126 suppressed the effect of upregulation of ERK1/2 phosphorylation and decreased cell proliferation, survival, and Schwann-like cell differentiation partially induced by 7, 8-DHF. In vivo, 7, 8-DHF promotes survival of transplanted BMSCs and upregulates axonal growth and myelination in regenerating ANAs. 7, 8-DHF+BMSCs also improved motor endplate density of target musculature. These benefits were associated with increased motor functional recovery. 7, 8-DHF+BMSCs significantly upregulated TrkB and ERK1/2 phosphorylation expression in regenerating ANA, and increased TrkB expression in the lumbar spinal cord. The mechanism of 7, 8-DHF action may be related to its ability to upregulate TrkB signaling, and downstream activation of survival signaling molecules ERK1/2 in the regenerating ANAs and spinal cord and improved survival of transplanted BMSCs. This study provides novel foundational data connecting the benefits of 7, 8-DHF treatment in neural injury and repair to BMSCs biology and function and demonstrates a potential combination approach for the treatment of injured peripheral nerve via nerve graft transplant.
登录
查看更多内容
影响因子：
5.3
作者：
Okada, Kiyoshi;Tanaka, Hiroyuki;Yoshikawa, Hideki
通讯作者：
Yoshikawa, Hideki
影响因子：
3.1
作者：
Gonzalez-Lara, Laura E.;Xu, Xiaoyun;Foster, Paula J.
通讯作者：
Foster, Paula J.
影响因子：
2.5
作者：
Byers, James S.;Huguenard, Anna L.;Kuruppu, Dulanji;Liu, Nai-Kui;Xu, Xiao-Ming;Sengelaub, Dale R.
通讯作者：
Sengelaub, Dale R.
影响因子：
5.3
作者：
DEMEDINACELI, L;FREED, WJ;WYATT, RJ
通讯作者：
WYATT, RJ
影响因子：
1.7
作者：
Kishino, A;Katayama, N;Nakayama, C
通讯作者：
Nakayama, C