Zhao Lei, Feng Yetong, Chen Xin, Yuan Jing, Liu Xiaobo, Chen Yaoyu, Zhao Yifan, Liu Pengfei, Li Yalan
Department of Anesthesiology, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, PR China.
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China.
Life Sci. 2016 Apr 15;151:93-101. doi: 10.1016/j.lfs.2016.03.001. Epub 2016 Mar 2.
Umbilical cord derived mesenchymal stem cells (UC-MSCs) have been demonstrated to hold the potential to be applied in the treatment of kinds of disease. In recent years, some scientists have differentiated the cells into neural progenitor cells (NPCs) successfully, providing a new cell source for neural disease therapy. However, the differentiation methods still need to be improved for the clinical studies in the future. In this study, insulin-like growth factor-1 (IGF-1) was tested to ameliorate UC-MSCs neural differentiation.
IGF-1 overexpressing UC-MSCs (UC-MSCs-IGF-1) were established through retroviral infection, and further differentiated into NPCs through neural induction. The proliferation and differentiation ability of UC-MSCs derived NPCs were evaluated respectively and the associated signaling mechanisms were further analyzed with RNA microarray, qPCR and western-blot.
Compared with NPCs from normal UC-MSCs, the NPCs derived from UC-MSCs-IGF-1 hold better proliferation ability and more Pax6-positive cells and Nestin-positive cells. Moreover, the UC-MSCs-IGF-1 derived NPCs could differentiate into astrocyte with higher efficiency during the process of terminal differentiation in vitro. RNA microarray analysis indicated that some key genes associated with neural differentiation and NPCs proliferation were upregulated, which were also confirmed with qPCR and western-blot. Finally, NPCs from UC-MSCs-IGF-1 transfected with IGF-1-siRNA showed a decrease of proliferation ability and astrocyte differentiation.
This study indicated that IGF-1 could improve neural differentiation of human UC-MSCs and provided a novel strategy to enhance astrocyte differentiation of NPCs from UC-MSCs.
脐带间充质干细胞（UC-MSCs）已被证明具有应用于多种疾病治疗的潜力。近年来，一些科学家已成功将这些细胞分化为神经祖细胞（NPCs），为神经疾病治疗提供了一种新的细胞来源。然而，未来的临床研究仍需改进分化方法。在本研究中，检测了胰岛素样生长因子-1（IGF-1）对改善UC-MSCs神经分化的作用。
通过逆转录病毒感染建立过表达IGF-1的UC-MSCs（UC-MSCs-IGF-1），并通过神经诱导进一步分化为NPCs。分别评估UC-MSCs来源的NPCs的增殖和分化能力，并用RNA微阵列、qPCR和western印迹进一步分析相关信号机制。
与正常UC-MSCs来源的NPCs相比，UC-MSCs-IGF-1来源的NPCs具有更好的增殖能力，且Pax6阳性细胞和巢蛋白阳性细胞更多。此外，UC-MSCs-IGF-1来源的NPCs在体外终末分化过程中能更高效地分化为星形胶质细胞。RNA微阵列分析表明，一些与神经分化和NPCs增殖相关的关键基因上调，qPCR和western印迹也证实了这一点。最后，用IGF-1-siRNA转染的UC-MSCs-IGF-1来源的NPCs增殖能力和星形胶质细胞分化降低。
本研究表明IGF-1可改善人UC-MSCs的神经分化，并为增强UC-MSCs来源的NPCs的星形胶质细胞分化提供了一种新策略。
