hPSC-derived sacral neural crest cells restore erectile function in pelvic ganglia injury.

BACKGROUND

Pelvic surgeries frequently injure the pelvic autonomic plexus, represented in rats by the major pelvic ganglia (MPG), resulting in refractory erectile dysfunction (ED) with limited therapeutic options. Sacral neural crest (NC) cells, the embryonic progenitors of MPG neurons and glial cells, offer a developmentally matched cell source for targeted neural repair.

METHODS

We developed a stable and expandable sacral NC cell population derived from human pluripotent stem cells (hPSCs) and transplanted these cells into a rat model of MPG crush injury to assess engraftment efficacy and functional outcomes.

RESULTS

Transplantation of sacral NC cells resulted in robust engraftment and significant erectile functional recovery, as evidenced by elevated intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios. Mechanistically, MPG repair involves dual pathways: differentiation into nitrergic and cholinergic neurons and glial cells, which is coupled with the sustained secretion of neurotrophic factors (BDNF/GDNF/NGF). MPG restoration thereby re-established autonomic innervation of the penis, driving structural recovery characterized by reduced apoptosis and fibrosis, as well as the restoration of smooth muscle and endothelial integrity-essential for erectile functional rehabilitation.

CONCLUSIONS

Our results demonstrate that hPSC-derived sacral NC cells represent a novel therapeutic strategy for neurogenic ED, restoring pelvic autonomic nerve structure and function through both neurogenic differentiation and sustained neurotrophic support.