Pro-angiogenic scaffold-free Bio three-dimensional conduit developed from human induced pluripotent stem cell-derived mesenchymal stem cells promotes peripheral nerve regeneration

Abstract

Although autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects, harvesting autologous nerves is highly invasive and leads to functional loss of the ablated part. In response, artificial nerve conduits made of artificial materials have been reported, but the efficacy of the nerve regeneration still needs improvement. The purpose of this study is to investigate the efficacy and mechanism of the Bio three-dimensional (3D) conduit composed of xeno-free human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs). The 5-mm nerve gap of the sciatic nerve in immunodeficient rats was bridged with the Bio 3D conduit or silicone tube. Functional and histological recovery were assessed at 8 weeks after surgery. The regenerated nerve in the Bio 3D group was significantly superior to that in the silicone group based on morphology, kinematics, electrophysiology, and wet muscle weight. Gene expression analyses demonstrated neurotrophic and angiogenic factors. Macroscopic observation revealed neovascularization both inside and on the surface of the Bio 3D conduit. Upon their subcutaneous implantation, iMSCs could induce angiogenesis. The Bio 3D conduit fabricated from iMSCs are an effective strategy for nerve regeneration in animal model. This technology will be useful in future clinical situations.