Generation and application of human pluripotent stem cells derived peri-nervoids
- 1Beijing Jishuitan Hospital, Capital Medical University
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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BibTeX
@misc{guan2026generation,
title = {{Generation and application of human pluripotent stem cells derived peri-nervoids}},
author = {Y. Guan and R. He and Z. Xiang and Y. Ouyang and H. Liu and S. Zhang and X. Liu and C. Liu and Z. Wang and Y. Wang and S. Chen},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.750880},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.750880v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Generation and application of human pluripotent stem cells derived peri-nervoids
AU - Y. Guan
AU - R. He
AU - Z. Xiang
AU - Y. Ouyang
AU - H. Liu
AU - S. Zhang
AU - X. Liu
AU - C. Liu
AU - Z. Wang
AU - Y. Wang
AU - S. Chen
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.750880
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.750880v1
AB - 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.
ER -