Human Umbilical Cord-Derived Mesenchymal Stromal Cells Differentiate Into Functional Schwann Cells That Sustain Peripheral Nerve Regeneration

Abstract

Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) that are available from cell banks can be induced to differentiate into various cell types, thereby making them practical potential sources for cell-based therapies. In injured peripheral nerves, Schwann cells (SCs) contribute to functional recovery by supporting axonal regeneration and myelin reconstruction. Here, we first demonstrate a system to induce UC-MSCs to differentiate into cells with SC properties (UC-SCs) by treatment with β-mercaptoethanol followed by retinoic acid and a set of specific cytokines. The UC-SCs are morphologically similar to SCs and express SC markers, including P0, as assessed by immunocytochemistry and reverse transcription polymerase chain reaction. Transplantation of UC-SCs into transected sciatic nerves in adult rats enhanced nerve regeneration. The effectiveness of UC-SCs for axonal regeneration was comparable to that of authentic human SCs based on histological criteria and functional recovery. Immunohistochemistry and immunoelectron microscopy also demonstrated myelination of regenerated axons by UC-SCs. These findings indicate that cells with SC properties and with the ability to support axonal regeneration and reconstruct myelin can be successfully induced from UC-MSCs to promote functional recovery after peripheral nerve injury. This system may be applicable for the development of cell-based therapies.