Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury.
Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury.
复制标题
降钙素基因相关肽是移植的人间充质干细胞归巢至脊髓损伤部位的关键因素
DOI：
10.1038/srep27724
复制
发表时间：
2016-06-14
影响因子：
4.6
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zhang Y;Yang J;Zhang P;Liu T;Xu J;Fan Z;Shen Y;Li W;Zhang H
间充质干细胞（MSC）可用于治疗许多疾病，包括脊髓损伤（SCI）。治疗主要依赖于细胞精确导航到损伤部位以重建受损的脊髓。然而，引导 MSC 到达 SCI 中心的关键因素仍不清楚。在这里，我们证明降钙素基因相关肽（CGRP）是一种在脊髓中合成的神经肽，可以极大地帮助脊髓横断的 SCI 大鼠中人脐带间充质干细胞（HUMSC）的归巢。首先，HUMSC 在体外表现出对 CGRP 的趋化反应。通过延时视频分析，趋化指数（CMI）、向前迁移指数（FMI）和速度的增加导致了这种观察到的迁移。然后，通过酶联免疫分析，观察到损伤后病变部位的CGRP浓度较高。 CGRP 的释放将 HUMSC 引导至损伤部位，而 CGRP 8-37（一种 CGRP 拮抗剂）可抑制损伤部位。我们还验证了 PI3K/Akt 和 p38MAPK 信号通路在 CGRP 诱导的 HUMSC 趋化迁移中发挥着关键作用。总的来说，我们的数据表明，CGRP 是帮助 HUMSC 迁移到病变部位的关键趋化因子，因此可以用作研究 SCI 后 MSC 归巢的模型分子。
Mesenchymal stem cells (MSCs) can be used to treat many diseases, including spinal cord injury (SCI). Treatment relies mostly on the precise navigation of cells to the injury site for rebuilding the damaged spinal cord. However, the key factors guiding MSCs to the epicenter of SCI remain unknown. Here, we demonstrated that calcitonin gene-related peptide (CGRP), a neural peptide synthesized in spinal cord, can dramatically aid the homing of human umbilical cord mesenchymal stem cells (HUMSCs) in spinal cord-transected SCI rats. First, HUMSCs exhibited chemotactic responsesin vitroto CGRP. By time-lapse video analysis, increased chemotactic index (CMI), forward migration index (FMI) and speed contributed to this observed migration. Then, through enzyme immunoassay, higher CGRP concentrations at the lesion site were observed after injury. The release of CGRP directed HUMSCs to the injury site, which was suppressed by CGRP 8–37, a CGRP antagonist. We also verified that the PI3K/Akt and p38MAPK signaling pathways played a critical role in the CGRP-induced chemotactic migration of HUMSCs. Collectively, our data reveal that CGRP is a key chemokine that helps HUMSCs migrate to the lesion site and thereby can be used as a model molecule to study MSCs homing after SCI.