Transplantation of Chemically Induced Human Fibroblast-Derived Cells Enhances Functional Recovery in a Common Marmoset Model of Spinal Cord Injury.

Abstract

Spinal cord injury (SCI) is incurable and often leads to permanent motor dysfunction, paralysis, and sensory impairment. We previously developed a method to directly reprogram human fibroblasts into neuron-like cells using only chemical compounds. In a rat model of SCI, we transplanted chemically reprogrammed cells, termed immature chemical-induced neuron-like (CiN) cells, derived using the developed method with slight modifications and found that the immature CiN cells exhibited therapeutic efficacy in SCI. As primate models more closely mimic humans than rat models, primate experiments are required to more accurately assess the safety and efficacy of immature CiN cells before their use in humans. Therefore, in this study, we aimed to determine the therapeutic efficacy of immature CiN cell transplantation in a marmoset SCI model. Immature CiN cells were transplanted into a subacute marmoset model of SCI on Day 9 after contusion injury, and the therapeutic efficacy was assessed. Motor recovery after SCI was assessed based on spontaneous motor activity and the original open-field rating scale over six weeks, after which the spinal cord at the injury site was subjected to histopathological and MRI analyses. Animals transplanted with immature CiN cells exhibited significantly enhanced motor recovery compared to control animals, consistent with improved nerve recovery or preservation. Our findings suggest that immature CiN cells can effectively treat SCI in primates.