Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, Coral Gables, Florida 33156, United States.
Biomedical Nanotechnology Institute at the University of Miami (BioNIUM), University of Miami, 1951 NW Seventh Avenue Suite 475, Miami, Florida 33136, United States.
ACS Biomater Sci Eng. 2020 Oct 12;6(10):5771-5784. doi: 10.1021/acsbiomaterials.0c00844. Epub 2020 Sep 14.
An important role of neural stem cell transplantation is repopulating neural and glial cells that actively promote repair following spinal cord injury (SCI). However, stem cell survival after transplantation is severely hampered by the inflammatory environment that arises after SCI. Biomaterials have a demonstrated history of managing post-SCI inflammation and can serve as a vehicle for stem cell delivery. In this study, we utilize macroporous polyethylene glycol (PEG) tubes, which were previously found to modulate the post-SCI microenvironment, to serve as a viable, soft substrate for injecting mouse embryonic day 14 (E14) spinal progenitors 2 weeks after tube implantation into a mouse SCI model. At 2 weeks after transplantation (4 weeks after injury), 4.3% of transplanted E14 spinal progenitors survived when transplanted directly into tubes compared to 0.7% when transplanted into the injury alone. Surviving E14 spinal progenitors exhibited a commitment to the neuronal lineage at 4 weeks post-injury, as assessed by both early and late phenotypic markers. Mice receiving tubes with E14 spinal progenitor transplantations had on average 21 ± 4 axons/mm regenerated compared to 8 ± 1 axons/mm for the injury only control, which corresponded with a significant increase in remyelination compared to the injury only control, while all conditions exhibited improved forelimb control 4 weeks after injury compared to the injury only. Collectively, we have demonstrated the feasibility of using PEG tubes to modify the implantation site and improve survival of transplanted E14 spinal progenitors.
神经干细胞移植的一个重要作用是补充在脊髓损伤（SCI）后积极促进修复的神经和神经胶质细胞。然而，干细胞在移植后的存活受到 SCI 后产生的炎症环境的严重阻碍。生物材料在管理 SCI 后的炎症方面有着显著的历史，可以作为干细胞输送的载体。在这项研究中，我们利用大孔聚乙二醇（PEG）管，这些管以前被发现可以调节 SCI 后的微环境，作为一种可行的、柔软的基质，用于在将 E14 脊髓祖细胞注射到 SCI 模型 2 周后将其移植到管中。在移植后 2 周（损伤后 4 周），与直接移植到损伤部位的 0.7%相比，直接移植到管中的 E14 脊髓祖细胞中有 4.3%存活。存活的 E14 脊髓祖细胞在损伤后 4 周时表现出向神经元谱系的定向，这可以通过早期和晚期表型标志物来评估。与仅损伤对照相比，接受 E14 脊髓祖细胞移植的管内的小鼠平均有 21 ± 4 个轴突/mm 再生，而仅损伤对照的有 8 ± 1 个轴突/mm 再生，这与与仅损伤对照相比，髓鞘再生有显著增加，而所有条件在损伤后 4 周时与仅损伤对照相比，前肢控制均有改善。总的来说，我们已经证明了使用 PEG 管来修饰植入部位并提高移植的 E14 脊髓祖细胞存活率的可行性。
