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IPSC-Derived Sensory Neurons Directing Fate Commitment of Human BMSC-Derived Schwann Cells: Applications in Traumatic Neural Injuries
oleh: Kin-Wai Tam, Cheuk-Yin Wong, Kenneth Lap-Kei Wu, Guy Lam, Xiaotong Liang, Wai-Ting Wong, Maximilian Tak-Sui Li, Wing-Yui Liu, Sa Cai, Graham Ka-Hon Shea, Daisy Kwok-Yan Shum, Ying-Shing Chan
Format: | Article |
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Diterbitkan: | MDPI AG 2023-05-01 |
Deskripsi
The in vitro derivation of Schwann cells from human bone marrow stromal cells (hBMSCs) opens avenues for autologous transplantation to achieve remyelination therapy for post-traumatic neural regeneration. Towards this end, we exploited human induced pluripotent stem-cell-derived sensory neurons to direct Schwann-cell-like cells derived from among the hBMSC-neurosphere cells into lineage-committed Schwann cells (hBMSC-dSCs). These cells were seeded into synthetic conduits for bridging critical gaps in a rat model of sciatic nerve injury. With improvement in gait by 12-week post-bridging, evoked signals were also detectable across the bridged nerve. Confocal microscopy revealed axially aligned axons in association with MBP-positive myelin layers across the bridge in contrast to null in non-seeded controls. Myelinating hBMSC-dSCs within the conduit were positive for both MBP and human nucleus marker HuN. We then implanted hBMSC-dSCs into the contused thoracic cord of rats. By 12-week post-implantation, significant improvement in hindlimb motor function was detectable if chondroitinase ABC was co-delivered to the injured site; such cord segments showed axons myelinated by hBMSC-dSCs. Results support translation into a protocol by which lineage-committed hBMSC-dSCs become available for motor function recovery after traumatic injury to both peripheral and central nervous systems.