Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury.
Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury.
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DOI：
10.1177/0963689718780309
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发表时间：
2018-07
影响因子：
3.3
通讯作者：
Matsumine A
中科院分区：
文献类型：
--
作者：
Takahashi A;Nakajima H;Uchida K;Takeura N;Honjoh K;Watanabe S;Kitade M;Kokubo Y;Johnson WEB;Matsumine A
使用间充质间质细胞（MSC）移植修复损伤的脊髓在临床前模型中显示出一致的益处。然而，移植骨髓间充质干细胞成活率低是一个重要的问题。在受伤的脊髓中，移植细胞暴露于缺氧条件下，并暴露于血管供应不良引起的营养缺乏。此外，移植的间充质干细胞面临导致细胞死亡的细胞毒性应激源。本研究的目的是比较从单个C57BL6/J小鼠中分离的脂肪来源的MSCs （AD-MSCs）和骨髓来源的MSCs （BM-MSCs）在以下方面的关系：(i)细胞特性，（ii）对缺氧、氧化应激和无血清条件的耐受性，以及（iii）移植后的细胞存活率。AD-MSCs和BM-MSCs表现出相似的细胞表面标记谱，但表达不同水平的生长因子和细胞因子。将两种基质细胞分别在20.5% O2和1.0% O2条件下培养7 d，研究基质细胞的相对抗逆性。结果表明，在低氧条件下，AD-MSCs比BM-MSCs具有更强的增殖能力和更大的培养活力。在h2o2诱导的氧化应激和无血清培养基中培养MSCs诱导应激。AD-MSCs比BM-MSCs更能耐受这些应激条件；同样，当在体内将AD-MSC移植到脊髓损伤区时，移植后的AD-MSC存活率更高。此外，与BM-MSC移植组相比，这种增加的AD-MSC移植后的存活率与轴突的保存和血管化的增强有关，这与抗γ同型蛋白激酶C和CD31免疫反应性的增加有关。因此，我们的研究结果表明，AD-MSCs是一种有吸引力的替代BM-MSCs治疗严重脊髓损伤的方法。然而，值得注意的是，两组在中度脊髓损伤后运动功能同样得到改善，但不幸的是，两组在严重脊髓损伤后均未见明显改善。
The use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular supply. Also, the transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this study was to compare adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs) isolated from individual C57BL6/J mice in relation to: (i) cellular characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free conditions, and (iii) cellular survival rates after transplantation. AD-MSCs and BM-MSCs exhibited a similar cell surface marker profile, but expressed different levels of growth factors and cytokines. To research their relative stress tolerance, both types of stromal cells were incubated at 20.5% O2 or 1.0% O2 for 7 days. Results showed that AD-MSCs were more proliferative with greater culture viability under these hypoxic conditions than BM-MSCs. The MSCs were also incubated under H2O2-induced oxidative stress and in serum-free culture medium to induce stress. AD-MSCs were better able to tolerate these stress conditions than BM-MSCs; similarly when transplanted into the spinal cord injury region in vivo, AD-MSCs demonstrated a higher survival rate post transplantation Furthermore, this increased AD-MSC survival post transplantation was associated with preservation of axons and enhanced vascularization, as delineated by increases in anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an attractive alternative to BM-MSCs for the treatment of severe spinal cord injury. However, it should be noted that the motor function was equally improved following moderate spinal cord injury in both groups, but with no significant improvement seen unfortunately following severe spinal cord injury in either group.
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