Associate Researcher Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, China
Abstract: Induced pluripotent stem cells (iPSCs)-based therapy holds great potential for substituting neural loss in the spinal cord injury (SCI), however, conventional cell therapies face the challenges of poor survival, inadequate neuronal differentiation, as well as the lack of vasculatures that supplies nutrients and regulates neurogenesis. Here, we employed self-assembling Nucleic-Acid-nanostructures-decorated-living-Cells (NACs) to create novel vascularized neural spheroids by combining hypoimmunogenic human motor neurons induced from iPSCs with human umbilical vein endothelial cells. Transplantation of vascularized neural spheroids into completely transected SCI mouse models results in a significant repair, as evidenced by their long-term survival and efficient differentiation into MNs, as well as function recovery of the bladder and hind limbs. Notably, these vascularized spheroids exhibited successful graft-host vascular connection, and more importantly, improved neurogenesis and functional restoration in mice compared to non-vascularized neural spheroids. Furthermore, these vascularized neural spheroids were transplanted into semi-transected SCI pig models and significantly improved motor functions, allowing their treatment in large animal models. Thus, this study reported a novel strategy to create vascularized neural spheroids and highlights the beneficial therapy of vascularization for SCI repair.
Funding Source: The National Natural Science Foundation of China (32400806)
