Autologous Neural Stem Cell Encapsulation in CT04-Integrated Fibrin Hydrogel Enhances Tissue Regeneration After Spinal Cord Injury in Monkeys

Spinal cord injury (SCI) is a major traumatic insult that leads to significant motor and sensory impairments. Following SCI, an inhibitory microenvironment develops, accompanied by substantial neuronal loss. A single therapeutic approach may not achieve substantial functional recovery. Therefore, strategies aimed at addressing the inhibitory environment and enhancing cellular engraftment are crucial for optimal recovery. In this study, we investigated the efficacy of combining an injectable fibrin hydrogel with subventricular zone-derived neural stem cells (SVZ-NSCs) and CT04, a RhoA inhibitor, in a rhesus monkey model of SCI. After characterizing SVZ-NSCs and optimizing the CT04 dosage, we administered the combination therapy during the sub-acute phase of SCI. Our results indicated that this combination treatment significantly improved neuronal differentiation and integration of grafted NSCs and promoted axonal regeneration. Compared to cell transplantation or CT04 treatment alone, animals receiving the combination therapy exhibited superior functional recovery. These findings highlight a promising approach for treating SCI by combining therapies to enhance NSC transplantation and axonal repair using an advanced injectable hydrogel.