Conjugated therapy with coaxially printed neural stem cell-laden microfibers and umbilical cord mesenchymal stem cell derived exosomes on complete transactional spinal cord defects
Xinda Li, Jin Zhang, Yi Zhang, Lili Guo, Mingjun Gao, Yangyang Wang, Wenqiao Qiu, Ying Yuan, Jianwei Zhu, Boxun Liu, Huan Xiong, Tao Xu, Ruxiang Xu
Abstract
Motor function recovery after complete spinal cord injury remained as a challenge in medical field, while one of the key approaches is promoting the local microenvironments. In this research, we performed a conjugated therapy by transplantation of neural stem cell (NSC) scaffolds and umbilical cord mesenchymal stem cell derived exosomes (ucMSC-exos) for the treatment of complete transactional spinal cord injury (SCI). We first demonstrated the anti-inflammatory effects of ucMSC-exos in vitro and found that ucMSC-exos could regulate microglia polarization from M1 to M2, an anti-inflammatory phenotype. Besides, ucMSC-exos also promoted NSC proliferation and neural differentiation during in vitro culturing. On the other hand, core-shell hydrogel microfibers were used as transplantation scaffolds for both small and large SCI defects. The core-shell microfibers could carry large amounts of NSCs in the core portion and the shell portion is highly permeable for nutrient and metabolite transportation. In in vivo experiments, we found that conjugated transplantation of ucMSC-exos and NSC microfibers could decreased inflammatory cytokines at lesion sites, gave rise to more neurons and promoted angiogenesis, thus comprehensively improved the local microenvironment while compared with transplantation of NSC scaffolds only. These beneficial results were in accordance with those in vitro experiments and further led to better locomotor function recovery. In summary, this research has demonstrated that that conjugated transplantation of ucMSC-exos and NSC microfibers could make a potential tool for complete SCI repair.