Comparisons of Neurotrophic Effects of Mesenchymal Stem Cells Derived from Different Tissues on Chronic Spinal Cord Injury Rats
Comparisons of Neurotrophic Effects of Mesenchymal Stem Cells Derived from Different Tissues on Chronic Spinal Cord Injury Rats
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DOI：
10.1089/scd.2021.0070
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发表时间：
2021-07-27
影响因子：
4
通讯作者：
Yuge, Louis
中科院分区：
文献类型：
--
作者：
Otsuka, Takashi;Maeda, Yuyo;Yuge, Louis
骨髓间充质干细胞（MSC）的细胞治疗被认为是脊髓损伤（SCI）的有前途的策略。由于来源组织的差异，MSC具有独特的特征。然而，相对较少的研究集中在来自不同组织的MSC的治疗效果的差异。本研究比较了脂肪组织来源的间充质干细胞、骨髓来源的间充质干细胞和颅骨来源的间充质干细胞（cMSCs）对慢性脊髓损伤模型大鼠的治疗作用。从收集的脂肪组织、骨髓和颅骨建立MSC。通过实时PCR分析每种MSC类型的神经营养因子表达。采用失重法建立大鼠脊髓损伤模型，脊髓损伤后4周静脉移植MSCs。从伤前到移植后4周评价后肢运动功能。采用实时荧光定量PCR和免疫印迹法检测脊髓组织中内源性神经营养因子和神经修复因子的表达。虽然细胞表面标志物和多能性的表达水平没有差异，但在cMSCs中Bdnf、Ngf和Sort 1（Nt-3）的表达相对较高。移植cMSCs可改善慢性脊髓损伤大鼠的运动功能。虽然移植细胞在损伤的SC组织中的植入程度没有差异，但cMSCs移植增强了损伤的SC组织中的BDNF、TrkB和Gap-43信使RNA表达和突触素蛋白表达。与其他组织来源的MSCs相比，cMSCs高表达多种神经营养因子，通过促进内源性神经营养因子和神经可塑性因子的表达，改善慢性脊髓损伤模型大鼠的运动功能。这些结果证明了cMSC在慢性SCI的基于细胞的治疗中的功效。
Cell-based therapies with mesenchymal stem cells (MSCs) are considered as promising strategies for spinal cord injury (SCI). MSCs have unique characteristics due to differences in the derived tissues. However, relatively few studies have focused on differences in the therapeutic effects of MSCs derived from different tissues. In this study, the therapeutic effects of adipose tissue-derived MSCs, bone marrow-derived MSCs, and cranial bone-derived MSCs (cMSCs) on chronic SCI model rats were compared. MSCs were established from the collected adipose tissue, bone marrow, and cranial bone. Neurotrophic factor expression of each MSC type was analyzed by real-time PCR. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 4 weeks after SCI. Hindlimb motor function was evaluated from before injury to 4 weeks after transplantation. Endogenous neurotrophic factor and neural repair factor expression in spinal cord (SC) tissue were examined by real-time PCR and western blot analyses. Although there were no differences in the expression levels of cell surface markers and multipotency, expression of Bdnf, Ngf, and Sort1 (Nt-3) was relatively higher in cMSCs. Transplantation of cMSCs improved motor function of chronic SCI model rats. Although there was no difference in the degree of engraftment of transplanted cells in the injured SC tissue, transplantation of cMSCs enhanced Bdnf, TrkB, and Gap-43 messenger RNA expression and synaptophysin protein expression in injured SC tissue. As compared with MSCs derived other tissues, cMSCs highly express many neurotrophic factors, which improved motor function in chronic SCI model rats by promoting endogenous neurotrophic and neural plasticity factors. These results demonstrate the efficacy of cMSCs in cell-based therapy for chronic SCI.