Blond McIndoe Laboratories, Regenerative Biomedicine, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
J Neurosci Res. 2012 Jul;90(7):1392-402. doi: 10.1002/jnr.23002. Epub 2012 Mar 15.
Transplantation of autologous Schwann cells (SCs) is a promising approach for treating various peripheral nerve disorders, including chronic denervation. However, given their drawbacks, such as invasive biopsy and lengthy culture in vitro, alternative cell sources would be needed. Adipose-derived stem cells (ASCs) are a candidate, and in this study rat ASCs transdifferentiated into a SC phenotype (dASC) cocultured with dorsal root ganglion neurons were shown to associate with neurites and to express myelin basic protein (MBP)-positive myelin protein. Furthermore, dASCs transplanted into a chronically denervated rat common peroneal nerve survived for at least for 10 weeks, maintaining their differentiated state. Immunohistochemical analysis revealed that transplanted dASCs associated with regenerating axons, forming MBP-/protein zero-positive myelin sheaths. The cell survival and myelin expression assessed by double labelling with S100 and glial fibrillary acidic protein were similar between the dASC- and SC-transplanted nerves. Importantly, transplantation of dASCs resulted in dramatically improved motor functional recovery and nerve regeneration, with a level comparable to, or even superior to, transplantation of SCs. In conclusion, dASCs are capable of myelinating axons in vivo and enhancing functional outcome after chronic denervation.
自体雪旺细胞（SCs）移植是治疗各种周围神经疾病的一种很有前途的方法，包括慢性去神经支配。然而，鉴于其自身的缺陷，如侵袭性活检和体外长时间培养，需要寻找其他的细胞来源。脂肪来源的干细胞（ASCs）是一种候选细胞，在这项研究中，大鼠 ASCs 转分化为雪旺细胞表型（dASC），与背根神经节神经元共培养后与神经突相关，并表达髓鞘碱性蛋白（MBP）阳性的髓鞘蛋白。此外，dASC 移植到慢性去神经支配的大鼠腓总神经中至少存活了 10 周，保持其分化状态。免疫组织化学分析显示，移植的 dASC 与再生轴突相关，形成 MBP-/蛋白零阳性的髓鞘鞘。通过 S100 和神经胶质纤维酸性蛋白双重标记评估的细胞存活和髓鞘表达在 dASC 和 SC 移植神经之间相似。重要的是，dASC 移植可显著改善慢性去神经支配后的运动功能恢复和神经再生，其效果与 SC 移植相当，甚至优于 SC 移植。总之，dASC 能够在体内髓鞘化轴突，并增强慢性去神经支配后的功能恢复。
