Kunming University of science and technology Kunming, Yunnan, China (People's Republic)
Abstract: Promoting axonal regeneration to fully restore functions after spinal cord injury (SCI) is a considerable challenge. Given that the regeneration in a complete SCI can realized for developing spinal cord (SC), we propose that SCI may achieve ideal repair if stimulating signal is enough to regress SCI to the developing state. To achieve substantial therapeutic outcome, here we develop a biodegradable hydrogel to co-encapsulate GMP-produced human neuroepithelial stem cells (NESCs) at neural tube stage and mesenchymal stem cells (MSCs) (NESC+MSC) and then transplant them into completely transected SCI rats at 4th thoracic vertebra and quarter-sectioned SCI adult monkeys at 10th thoracic vertebra. NESC+MSC grafts reverse injured SC into developing state resembling to postnatal day 1-3 along with inflammatory inhibition. Instead of cell direct replacement, NESC+MSC grafts elicit directed regrowth of reticulospinal neuron and propriospinal neuron axons to cross lesions, span at least ten spinal segments caudally to lumbar segments, and relay the supraspinal command to restore walking in paraplegic rats. Thus, reversing developing state forms an important strategy of axon regeneration to restore lost neurological functions.
Funding Source: This work was supported by grants from National Key R&D Program of China Major Basic Research Project of Science and Technology of Yunnan , Spring City Plan the High-level Talent Promotion and Training Project of Kunming.
