Recellularized nerve allografts with differentiated mesenchymal stem cells promote peripheral nerve regeneration

Chemical-extracted acellular nerve allografting, containing the natural nerve structure and elementary nerve extracellular matrix (ECM), has been used for peripheral nerve-defect treatment experimentally and clinically. However, functional outcome with acellular nerve allografting decreases with increased size of gap in nerve defects. Cell-based therapy is a good strategy for repairing long nerve defects. Bone-marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ADSCs) can be induced to differentiate into cells with Schwann cell-like properties (BMSC-SCs or ADSC-SCs), which have myelin-forming ability in vitro and secrete trophic nerve growth factors. Here, we aimed to determine whether BMSC-SCs or ADSC-SCs are a promising cell type for enriching acellular grafts in nerve repair. We evaluated axonal regeneration distance by immunofluorescence staining after 2-week implantation. We used functional and histomorphometric analysis to evaluate 3-month regeneration of the novel cell-supplemented tissue-engineered nerve graft used to bridge a 15-mm-long sciatic nerve gap in rats. Introducing BMSC-SCs or ADSC-SCs to the acellular nerve graft promoted sciatic nerve regeneration and functional recovery. Nerve regeneration with BMSC-SCs or ADSC-SCs was comparable to that with autografting and Schwann cells alone and better than that with acellular nerve allografting alone. Differentiated bone-marrow-or adipose-derived MSCs may be a promising cell source for tissue-engineered nerve grafts and promote functional recovery after peripheral nerve injury.