Kim Woo Keyoung, Kim Wan Hee, Kweon Oh-Kyeong, Kang Byung-Jae
Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.
BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul 08826, Korea.
Animals (Basel). 2020 Nov 20;10(11):2164. doi: 10.3390/ani10112164.
Transplantation of mesenchymal stem cells (MSCs) is a promising treatment for spinal cord injury (SCI). However, many transplanted cells die within a few days, eventually limiting the efficacy of cellular therapy. To overcome this problem, we focused on the potential of heat shock (HS) proteins in facilitating recovery from cell damage and protecting against cytotoxicity. PCR results showed that the expression of neurotrophic factor, anti-inflammatory, stemness, and homing genes increased in HS-treated MSCs. We investigated whether HS-treated MSCs could promote recovery of hindlimb function in an acute canine SCI model. We compared the effects of intravenous transplantation with (i) lactated Ringer's solution as a control, (ii) green fluorescent protein-expressing MSCs (MSCs-GFP), and (iii) GFP-expressing and HS-treated MSCs (MSCs-GFP-HS). Spinal cords were harvested at four weeks and used for Western blot and histopathological analyses. The MSCs-GFP-HS group showed significant improvements in hindlimb function from weeks 3 and 4 compared with the other groups. This group also showed higher expression of neural markers, fewer intervening fibrotic changes, and pronounced myelination. These results suggest that induction of an HS response in MSCs could promote neural sparing. In conclusion, transplantation of HS-treated MSCs could improve neuroprotection and neuroregeneration in acute SCI.
间充质干细胞（MSCs）移植是治疗脊髓损伤（SCI）的一种很有前景的方法。然而，许多移植细胞在几天内死亡，最终限制了细胞治疗的效果。为了克服这个问题，我们关注热休克（HS）蛋白在促进细胞损伤恢复和抵抗细胞毒性方面的潜力。PCR结果显示，热休克处理的间充质干细胞中神经营养因子、抗炎、干性和归巢基因的表达增加。我们研究了热休克处理的间充质干细胞是否能促进急性犬脊髓损伤模型后肢功能的恢复。我们比较了静脉移植（i）乳酸林格氏液作为对照、（ii）表达绿色荧光蛋白的间充质干细胞（MSCs-GFP）和（iii）表达绿色荧光蛋白且经热休克处理的间充质干细胞（MSCs-GFP-HS）的效果。四周时采集脊髓用于蛋白质免疫印迹和组织病理学分析。与其他组相比，MSCs-GFP-HS组在第3周和第4周时后肢功能有显著改善。该组还显示神经标志物表达更高、中间纤维化变化更少且髓鞘形成明显。这些结果表明，诱导间充质干细胞产生热休克反应可促进神经保护。总之，热休克处理的间充质干细胞移植可改善急性脊髓损伤中的神经保护和神经再生。
