Department of Bioengineering, University of California, Berkeley, California, 94720, USA.
UC Berkeley-UCSF Graduate Program in Bioengineering, Berkeley, California, 94720, USA.
Sci Rep. 2017 Dec 12;7(1):17401. doi: 10.1038/s41598-017-17043-4.
In regenerative medicine applications, the differentiation stage of implanted stem cells must be optimized to control cell fate and enhance therapeutic efficacy. We investigated the therapeutic potential of human induced pluripotent stem cell (iPSC)-derived cells at two differentiation stages on peripheral nerve regeneration. Neural crest stem cells (NCSCs) and Schwann cells (NCSC-SCs) derived from iPSCs were used to construct a tissue-engineered nerve conduit that was applied to bridge injured nerves in a rat sciatic nerve transection model. Upon nerve conduit implantation, the NCSC group showed significantly higher electrophysiological recovery at 1 month as well as better gastrocnemius muscle recovery at 5 months than the acellular group, but the NCSC-SC group didn't. Both transplanted NCSCs and NCSC-SCs interacted with newly-growing host axons, while NCSCs showed better survival rate and distribution. The transplanted NCSCs mainly differentiated into Schwann cells with no teratoma formation, and they secreted higher concentrations of brain-derived neurotrophic factor and nerve growth factor than NCSC-SCs. In conclusion, transplantation of iPSC-NCSCs accelerated functional nerve recovery with the involvement of stem cell differentiation and paracrine signaling. This study unravels the in vivo performance of stem cells during tissue regeneration, and provides a rationale of using appropriate stem cells for regenerative medicine.
在再生医学应用中，必须优化植入干细胞的分化阶段，以控制细胞命运并提高治疗效果。我们研究了人诱导多能干细胞（iPSC）衍生细胞在周围神经再生的两个分化阶段的治疗潜力。我们使用 iPSC 衍生的神经嵴干细胞（NCSC）和施万细胞（NCSC-SC）构建了组织工程神经导管，将其应用于大鼠坐骨神经横断模型中损伤神经的桥接。神经导管植入后，NCSC 组在 1 个月时表现出明显更高的电生理恢复，在 5 个月时表现出更好的比目鱼肌恢复，优于无细胞组，但 NCSC-SC 组没有。两种移植的 NCSC 和 NCSC-SC 均与新生长的宿主轴突相互作用，而 NCSC 显示出更好的存活率和分布。移植的 NCSC 主要分化为施万细胞，没有形成畸胎瘤，并且它们分泌的脑源性神经营养因子和神经生长因子浓度高于 NCSC-SC。总之，iPSC-NCSC 的移植加速了功能神经的恢复，涉及干细胞分化和旁分泌信号。这项研究揭示了干细胞在组织再生过程中的体内表现，并为再生医学中使用适当的干细胞提供了依据。
