Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation
Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation
复制标题
三维培养中的骨髓间充质干细胞通过神经营养保护和免疫调节促进神经元再生。
DOI：
10.1002/jbm.a.35708
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发表时间：
2016-07-01
影响因子：
4.9
通讯作者：
Dai, Jianwu
中科院分区：
文献类型：
--
作者：
Han, Sufang;Wang, Bin;Dai, Jianwu
越来越多的证据表明，与传统的二维(2D)培养相比，三维(3D)培养可以更好地模拟体内干细胞的生态位。在本研究中，我们发现骨髓间充质干细胞(BMSCs)在三维胶原支架(3D BMSCs)中培养具有显著的特征，包括显著促进神经营养因子的分泌和降低脂多糖(LPS)刺激的巨噬细胞的激活。为了进一步评价3D BMSCs对脊髓损伤(SCI)再生的潜在益处，将3D BMSCs和2D BMSCs分别植入大鼠脊髓半横断损伤处。与2D组相比，3DBMSCs移植组移植后5d时炎性细胞因子的表达明显减少，8周内明显促进轴突再生，促进运动功能恢复。诺可达唑解聚3D BMSCs细胞骨架时，神经营养因子和炎性细胞因子的表达变化至少部分被钝化。因此，3D BMSCs的神经元保护和免疫调节的协同作用可能导致脊髓损伤功能的更好恢复，其潜在机制可能涉及3D培养导致其细胞形态的改变。本研究有助于更好地了解3D BMSCs的细胞特性，为促进脊髓损伤的修复提供新的策略。(C)2016 Wiley期刊，Inc.生物材料资源A部分：104A：1759-1769,2016。
Accumulating evidence has revealed three-dimensional (3D) culture could better mimic the stem cell niche in vivo in comparison with conventional two-dimensional (2D) culture. In this study, we found that bone marrow derived mesenchymal stem cells (BMSCs) cultured in 3D collagen scaffold (3D BMSCs) exhibited distinctive features including significantly enhancing neurotrophic factor secretions and reducing macrophage activations challenged by lipopolysaccharide (LPS) in vitro. To further evaluate 3D BMSCs' potential benefits to the regeneration of spinal cord injury (SCI), the 3D and 2D BMSCs were respectively implanted in rat hemisected SCI. Compared with 2D cohort, 3D BMSCs transplantation significantly reduced the expressions of inflammatory cytokines such as TNF-, IL-1, and IL-6 at 5 days after transplantation, markedly enhanced axonal regeneration, and promoted motor functional recovery during 8 weeks of observation. When Nocodazole was used to depolymerize the cytoskeleton of 3D BMSCs, the changed expressions of neurotrophic factors and inflammatory cytokines were blunted, at least partially. Thus synergistic effects of neuronal protection and immunomodulation of 3D BMSCs may lead to a better functional recovery of SCI and the underlying mechanism may involve the alteration of their cellular morphology because of 3D culture. This study contributes to a better understanding of the cellular characteristics of 3D BMSCs and provides a novel strategy to promote the repair of the injured spinal cord. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1759-1769, 2016.