Department of Neurosurgery, Spine & Spinal Cord Institute, College of Medicine, Yonsei University, Shinchon-dong, Seodaemon-ku, Seoul 120-750, Republic of Korea.
Neurosci Lett. 2010 Mar 26;472(3):215-9. doi: 10.1016/j.neulet.2010.02.008. Epub 2010 Feb 11.
Hypoxic preconditioning (HP) is a novel strategy to make stem cells resistant to the ischemic environment they encounter after transplantation into injured tissue; this strategy improves survival of both the transplanted cells and the host cells at the injury site. Using both in vitro and in vivo injury models, we confirmed that HP-treated adipose tissue-derived mesenchymal stem cells (HP-AT-MSCs) increased cell survival and enhanced the expression of marker genes in DsRed-engineered neural stem cells (NSCs-DsRed). Similar to untreated AT-MSCs, HP-AT-MSCs had normal morphology and were positive for the cell surface markers CD90, CD105, and CD29, but not CD31. In three in vitro ischemic-mimicking injury models, HP-AT-MSCs significantly increased both the viability of NSCs-DsRed and the expression of DsRed and clearly reduced the number of annexin-V-positive apoptotic NSCs-DsRed and the expression of the apoptotic factor Bax. Consistent with the in vitro assay, co-transplantation of NSCs-DsRed with HP-AT-MSCs significantly improved the survival of the NSCs-DsRed, resulting in an increased expression of the DsRed reporter gene at the transplantation site in a rat spinal cord injury (SCI) model. These findings suggest that the co-transplantation of HP-AT-MSCs with engineered NSCs can improve both the cell survival and the gene expression of the engineered NSCs, indicating that this novel strategy can be used to augment the therapeutic efficacy of combined stem cell and gene therapies for SCI.
缺氧预处理（HP）是一种使干细胞对移植到损伤组织后遇到的缺血环境具有抗性的新策略；该策略可提高移植细胞和损伤部位宿主细胞的存活率。我们使用体外和体内损伤模型证实，经过 HP 处理的脂肪组织源性间充质干细胞（HP-AT-MSCs）增加了细胞存活率，并增强了红色荧光蛋白（DsRed）标记的神经干细胞（NSCs-DsRed）中的标记基因的表达。与未处理的 AT-MSCs 相似，HP-AT-MSCs 具有正常的形态，并且阳性表达细胞表面标记物 CD90、CD105 和 CD29，但不表达 CD31。在三种体外模拟缺血损伤模型中，HP-AT-MSCs 显著增加了 NSCs-DsRed 的活力和 DsRed 的表达，并明显减少了 Annexin-V 阳性凋亡 NSCs-DsRed 的数量和凋亡因子 Bax 的表达。与体外检测结果一致，将 NSCs-DsRed 与 HP-AT-MSCs 共移植可显著提高 NSCs-DsRed 的存活率，导致在大鼠脊髓损伤（SCI）模型中移植部位 DsRed 报告基因的表达增加。这些发现表明，与工程化 NSCs 共移植 HP-AT-MSCs 可以提高工程化 NSCs 的细胞存活率和基因表达，表明这种新策略可用于增强 SCI 的联合干细胞和基因治疗的治疗效果。
