Intermediate cell states in spermatogonial stem cell differentiation: enhancing neurogenesis and angiogenesis in spinal cord injury.

BACKGROUND: Spermatogonial stem cells (SSCs) can differentiate into various cell types, including neurons. This study sought to evaluate the therapeutic effects of SSC-derived spinal cord neurons for spinal cord injury (SCI). METHODS: SSCs derived from rats were differentiated into spinal cord neurons. HUVECs were treated with SSC-conditioned medium (CM). Phase contrast imaging and immunofluorescence were used to evaluate the efficiency of neural transdifferentiation. The expression of glial cell-specific genes and angiogenic factors was detected by qRT-PCR. HUVEC migration was assessed using wound healing assay. Transdifferentiated spinal cord neurons were transplanted into SCI rats. The neural recovery of rats was assessed by immunofluorescence, HE staining, and BBB scoring. Subsequently, electrophysiological tests (MEPs and SEPs) and ultrasonography were conducted. RESULTS: SSCs were transdifferentiated into functional spinal cord neurons. The expression of glial cell-specific genes significantly increased after differentiation, suggesting the existence of an intermediate cell state during this process. SSC-CM markedly promoted HUVEC migration and increased the expression of angiogenic factors. Transdifferentiated neurons survived and maintained neuronal function after transplantation into SCI rats. Neuron transplantation improved spinal cord damage and motor function in SCI rats. Moreover, neuron transplantation improved the MEP and SEP parameters and promoted vascular regeneration in SCI rats. CONCLUSIONS: The intermediate cell state existing during SSC differentiation improves SCI by promoting neurogenesis and angiogenesis, offering a promising approach for spinal cord repair.