Generation of Functional\nNeurons from Mesenchymal\nStem Cells Using Neural Differentiator and Engineered Peptide Hydrogel:\nPotential Therapeutic Lead for Traumatic Brain Injury

Traumatic brain injuries (TBIs) cause multifaceted disruption\nin\nthe neural network, initiate huge inflammation processes, and form\nglial scars that result in severe damage to the brain. Thus, the treatment\nof TBI is a challenging task. To address this challenge, a newer and\ninnovative approach is extremely important to develop a successful\ntherapeutic strategy. Toward this aim, we hereby report an extremely\neffective therapeutic strategy. This interesting approach showcased\nthe development and validation of a combination therapy comprising\na neuro-regenerative protective peptide hydrogel (SLNAP) and a potent\nneuro-regenerative chemical modulator (NCM). It is noteworthy to mention\nthat this hydrogel formulation has injectable nature, which allows\nit to be applied at focal injury site of brain. Remarkably, our results\nreveal excellent transdifferentiation of human umbilical cord-derived\nmesenchymal stem cells (hMSCs) into functional neuron upon treatment\nwith this combination therapeutic formulation. The functionality of\nregenerated neurons was thoroughly checked through observation of\nactive signals generated from those neurons in electrophysiology recording\nusing patch clamp. Further, we also observed that this strategy not\nonly successfully converts hMSCs into neuron but also spontaneously\nformed neural stem cells (NSCs) like neurosphere. This work also showcased\nthat this multidomain self-assembling peptide hydrogel emerges as\nan attractive soft-biomaterial due to its capability of slow and sustained\nrelease of the drug at the injury site upon topical application. This\nresulted in significant regeneration of functional neuron at the injury\nsite. Fascinatingly, we found that this combination therapeutic strategy\nis highly effective in <i>in vivo</i> brain injury model\nestablishing that this could be a potential and highly effective therapeutic\nstrategy for TBI.