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bioRxiv · 10.64898/2026.09.14.750880

Generation and application of human pluripotent stem cells derived peri-nervoids

Guan, Y.·He, R.·Xiang, Z.·Ouyang, Y.·Liu, H.·Zhang, S.·Liu, X.·Liu, C.·Wang, Z.·Wang, Y.·Chen, S.
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Abstract

Autologous nerve grafts remain the gold standard for peripheral nerve repair, but donor scarcity, donor-site morbidity and incomplete functional recovery limit their use. Schwann cells (SCs) drive autograft-mediated regeneration, yet their limited availability and expansion impede SC-based therapies. Here, we generated human pluripotent stem cell-derived SCs, motor neuron-enriched spinal cord organoids and nociceptive sensory neuron-enriched dorsal root ganglion organoids, and assembled them into a nerve-like construct termed the Peri-nervoid. Single-cell RNA sequencing revealed context-dependent SC plasticity: axonal co-culture promoted myelination, whereas axonal transection induced a repair phenotype resembling SC dedifferentiation during Wallerian degeneration. Following transplantation into 7-mm sciatic nerve defects in NSG mice, human SCs survived and remyelinated regenerating host axons, while axon-containing grafts enhanced regeneration relative to SC-only grafts. No abnormal proliferation, systemic toxicity or major-organ histopathology was detected. These findings position the Peri-nervoid as a scalable, developmentally inspired platform for developing engineered grafts for peripheral nerve repair.

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Guan, Y., He, R., Xiang, Z., Ouyang, Y., Liu, H., Zhang, S., Liu, X., Liu, C., Wang, Z., Wang, Y., Chen, S.. 2026-09-16. Generation and application of human pluripotent stem cells derived peri-nervoids. https://doi.org/10.64898/2026.09.14.750880

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