Human spinal GABA neurons survive and mature in the injured nonhuman primate spinal cord

Abstract

Spinal cord injury (SCI) leads to permanent neural dysfunction without effective therapies. We previously showed that human pluripotent stem cell (hPSC)-derived spinal GABA neurons can alleviate spasticity and promote locomotion in rats after SCI, but whether this strategy can be translated into the clinic remains elusive. Here, a nonhuman primate (NHP) model of SCI was established in rhesus macaques (Macaca mulatta) in which the T10 spinal cord was hemisected, resulting in neural conduction failure and neural dysfunction, including locomotion deficits, pain, and spasms. Grafted human spinal GABA neurons survived for up to 7.5 months in the injured monkey spinal cord and retained their intrinsic properties, becoming mature and growing axons and forming synapses. Importantly, they are functionally alive, as evidenced by designer receptors exclusively activated by designer drug (DREADD) activation. These findings represent a significant step toward the clinical translation of human spinal neuron transplantation for treating SCI.