IGF1c mimetic peptide-based supramolecular hydrogel microspheres synergize with neural stem cells to promote functional recovery from spinal cord injury

Abstract

Spinal cord injuries (SCI) often cause severe inflammatory response and neuronal loss, which consequently deteriorates motor function. Although exogenous stem cells are considered to be vital seed cells for cell replacement therapy after SCI, their low survival rate and low efficiency of neuronal differentiation after in vivo transplantation limit their widespread application in clinical practice. To this end, this study proposed a new strategy for dramatically improving the efficiency of insulin-like growth factor 1 (IGF1c) mimetic peptide to activate its receptor by fabricating IGF1c mimetic peptide supramolecular hydrogel microspheres (IGF1c-PHM) using an innovatively designed piezoelectric ceramic-driven thermal electrospray device. IGF1c-PHM displayed an average size of 10 µm and could activate the IGF1R of neural stem cells (NSCs) more effectively than IGF1c peptide block hydrogel (IGF1c-PH). In vitro, IGF1c-PHM exerted strong neuroprotective effects by maintaining the proliferation, inhibiting the apoptosis of NSCs, and promoting the efficiency of differentiation into neurons in presence of myelin extracts. In vivo, IGF1c-PHM improved the inflammatory environment by suppressing the recruitment of the inflammatory cells, altering the subtypes of the macrophages, and promoting the survival rate of endogenous cells and NSCs in the injury area. In particular, IGF1c-PHM enhanced the proliferation ability and neuronal differentiation of NSCs in vivo after SCI. In the presence of IGF1c-PHM, the transplanted NSCs could differentiate into several mature neurons at the injury site, and the axons regenerated in the injury site were remyelinated, all of which closely correlate with the improvement of the electrophysiological indices after SCI. Finally, at 8 weeks post-SCI, the gait analysis and behavioral scores confirmed the significant improvement in motor function in rats treated with IGF1c-PHM and NSCs. Therefore, IGF1c-PHM combined with NSCs is a promising therapy for treating SCI.