Regeneration of peripheral nerves by transplanted sphere of human mesenchymal stem cells derived from embryonic stem cells
Regeneration of peripheral nerves by transplanted sphere of human mesenchymal stem cells derived from embryonic stem cells
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DOI：
10.1016/j.biomaterials.2012.06.047
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发表时间：
2012-10-01
期刊：
影响因子：
14
通讯作者：
Kim, Hyo-Soo
中科院分区：
文献类型：
--
作者：
Lee, Eun Ju;Xu, Lianji;Kim, Hyo-Soo
在细胞治疗中，治疗效果最重要的因素是稳定的细胞供应和最佳的植入效率。为了满足这一要求，我们开发了一种培养策略，例如在无血清培养基中进行人胚胎干细胞来源的间充质干细胞（hESC-MSC）的三维球体培养。为了研究 hESC-MSC 球体在神经损伤模型中的体内治疗效果，我们横切无胸腺裸鼠的坐骨神经并产生 2 毫米的间隙。在 1) 神经传导（球体；28.81 +/- 3.55 与单细胞；18.04 +/- 2.10，p < 0.05）和 2) 低电压神经刺激敏感性（球体；0.38 +/- 0.08 与单细胞；p < 0.05）方面，hESC-MSC 作为球体移植修复受损神经的效果显着优于移植 hESC-MSC 作为悬浮单细胞； 8 周时为 0.66 +/- 0.11，p < 0.05）。与正常对照的数据相比，球体移植后的恢复接近完全（神经传导球体28.81 +/- 3.55与正常32.62 +/- 2.85：神经刺激敏感性球体0.38 +/- 0.08与正常0.36 +/- 0.67，分别没有显着差异）。再生神经的组织学证据充分证实了受损神经功能的恢复。在机制分析中，成球hESC-MSC上清液中肝细胞生长因子和胰岛素样生长因子结合蛋白-1的含量显着高于hESC-MSC单细胞上清液中的含量，这可能是提高移植效率和损伤周围神经更好再生的关键因素。 (C) 2012 Elsevier Ltd. 保留所有权利。
In cell therapy, the most important factor for therapeutic efficacy is the stable supply of cells with best engraftment efficiency. To meet this requirement, we have developed a culture strategy such as three-dimensional sphere of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in serum-free medium. To investigate the in vivo therapeutic efficacy of hESC-MSC spheres in nerve injury model, we transected the sciatic nerve in athymic nude mice and created a 2-mm gap. Transplantation of hESC-MSC as sphere repaired the injured nerve significantly better than transplantation of hESC-MSC as suspended single cells in regard to 1) nerve conduction (sphere; 28.81 +/- 3.55 vs. single cells; 18.04 +/- 2.10, p < 0.05) and 2) susceptibility of nerve stimulation at low voltage (sphere; 0.38 +/- 0.08 vs. single cells; 0.66 +/- 0.11, p < 0.05) at 8 weeks. Recovery after sphere transplantation was near-complete when compared with the data of normal control (sphere 28.81 +/- 3.55 vs normal 32.62 +/- 2.85 in nerve conduction : sphere 0.38 +/- 0.08 vs normal 0.36 +/- 0.67 in susceptibility of nerve stimulation, no significant difference, respectively). Recovery in function of the injured nerve was well corroborated by the histologic evidence of regenerated nerve. In the mechanistic analysis, the supernatant of sphere-forming hESC-MSC contains hepatocyte growth factor and insulin-like growth factor-binding protein-1 significantly more than the supernatant of the single cells of hESC-MSC has, which might be the key factors for the improved engraftment efficiency and greater regeneration of injured peripheral nerve. (C) 2012 Elsevier Ltd. All rights reserved.