Repair of extended peripheral nerve lesions in rhesus monkeys using acellular allogenic nerve grafts implanted with autologous mesenchymal stem cells

• Published in: Experimental neurology 2007-04, Vol.204 (2), p.658-666
• Main Authors: Hu, Jun, Zhu, Qing-Tang, Liu, Xiao-Lin, Xu, Yang-bin, Zhu, Jia-Kai
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Allogenic nerve graft; Analysis of Variance; Animals; Autograft; Biocompatible Materials - therapeutic use; Biological and medical sciences; Cells, Cultured; Cranial nerves. Peripheral nerves. Autonomic nervous system; Disease Models, Animal; Female; Injuries of the nervous system and the skull. Diseases due to physical agents; Macaca mulatta; Male; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Microscopy, Electron - methods; Muscle, Skeletal - innervation; Nerve Regeneration - physiology; Neural Conduction - physiology; Neurofilament Proteins - metabolism; Neurosurgery; Peripheral nerve; Peripheral Nervous System Diseases - surgery; Primates; Recovery of Function - physiology; Regeneration; Rhesus monkeys; Schwann cells; Schwann Cells - physiology; Schwann Cells - transplantation; Schwann Cells - ultrastructure; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Transplantation, Homologous - methods; Traumas. Diseases due to physical agents; Ulnar nerve
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2006.11.018

Despite intensive efforts in the field of peripheral nerve injury and regeneration, it remains difficult in humans to achieve full functional recovery following extended peripheral nerve lesions. Optimizing repair of peripheral nerve injuries has been hindered by the lack of viable and reliable biologic or artificial nerve conduits for bridging extended gaps. In this study, we utilized chemically extracted acellular allogenic nerve segments implanted with autologous non-hematopoietic mesenchymal stem cells (MSCs) to repair a 40 mm defect in the rhesus monkey ulnar nerve. We found that severely damaged ulnar nerves were structurally and functionally repaired within 6 months following placement of the MSC seeded allografts in all animals studied (6 of 6, 100%). Furthermore, recovery with the MSC seeded allografts was similar to that observed with Schwann cell seeded allografts and autologous nerve grafts. The findings presented here are the first demonstration of the successful use of autologous MSCs, expanded in culture and implanted in a biological conduit, to repair a peripheral nerve gap in primates. Given the difficulty in isolating and purifying sufficient quantities of Schwann cells for peripheral nerve regeneration, the use of MSCs to seed acellular allogenic nerve grafts may prove to be a novel and promising therapeutic approach for repairing severe peripheral nerve injuries in humans.