Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.
Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.
ACS Biomater Sci Eng. 2020 Feb 10;6(2):1165-1175. doi: 10.1021/acsbiomaterials.9b01557. Epub 2020 Jan 30.
Mesenchymal stem cell (MSC)-based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). However, low survival rate, uncontrollable migration, and differentiation of stem cells after implantation represent major challenges toward the clinical deployment of this approach. In this study, we fabricated three-dimensional MSC-laden microfibers via electrospinning in a rotating cell culture to mimic nerve tissue, control stem cell behavior, and promote integration with the host tissue. The hierarchically aligned fibrin hydrogel was used as the MSC carrier though a rotating method and the aligned fiber structure induced the MSC-aligned adhesion on the surface of the hydrogel to form microscale cell fibers. The MSC-laden microfiber implantation enhanced the donor MSC neural differentiation, encouraged the migration of host neurons into the injury gap and significantly promoted nerve fiber regeneration across the injury site. Abundant GAP-43- and NF-positive nerve fibers were observed to regenerate in the caudal, rostral, and middle sites of the injury position 8 weeks after the surgery. The NF fiber density reached to 29 ± 6 per 0.25 mm at the middle site, 82 ± 13 per 0.25 mm at the adjacent caudal site, and 70 ± 23 at the adjacent rostral site. Similarly, motor axons labeled with 5-hydroxytryptamine were significantly regenerated in the injury gap, which was 122 ± 22 at the middle injury site that was beneficial for motor function recovery. Most remarkably, the transplantation of MSC-laden microfibers significantly improved electrophysiological expression and re-established limb motor function. These findings highlight the combination of MSCs with microhydrogel fibers, the use of which may become a promising method for MSC implantation and SCI repair.
间充质干细胞（MSC）为基础的再生医学被广泛认为是一种有前途的方法，用于修复组织和重建脊髓损伤（SCI）的功能。然而，干细胞在植入后的低存活率、不可控迁移和分化是该方法向临床应用部署的主要挑战。在本研究中，我们通过旋转细胞培养中的静电纺丝制造了三维 MSC 负载微纤维，以模拟神经组织，控制干细胞行为，并促进与宿主组织的整合。分层排列的纤维蛋白水凝胶被用作 MSC 载体，通过旋转方法，排列的纤维结构诱导 MSC 在水凝胶表面排列黏附，形成微尺度细胞纤维。MSC 负载微纤维的植入增强了供体 MSC 的神经分化，促进了宿主神经元迁移到损伤间隙，并显著促进了神经纤维在损伤部位的再生。手术后 8 周，在损伤部位的尾部、头部和中部观察到大量 GAP-43 和 NF 阳性神经纤维再生。NF 纤维密度在中部达到 29±6 根/0.25mm，在相邻尾部达到 82±13 根/0.25mm，在相邻头部达到 70±23 根/0.25mm。同样，用 5-羟色胺标记的运动轴突在损伤间隙中也明显再生，在中部损伤部位达到 122±22 根，有利于运动功能的恢复。最显著的是，MSC 负载微纤维的移植显著改善了电生理表达，并重新建立了肢体运动功能。这些发现强调了 MSC 与微水凝胶纤维的结合，这种方法可能成为 MSC 植入和 SCI 修复的一种有前途的方法。
