Generation of Functional Neurons from Mesenchymal Stem Cells Using Neural Differentiator and Engineered Peptide Hydrogel: Potential Therapeutic Lead for Traumatic Brain Injury.

Abstract

Traumatic brain injuries (TBIs) cause multifaceted disruption in the neural network, initiate huge inflammation processes, and form glial scars that result in severe damage to the brain. Thus, the treatment of TBI is a challenging task. To address this challenge, a newer and innovative approach is extremely important to develop a successful therapeutic strategy. Toward this aim, we hereby report an extremely effective therapeutic strategy. This interesting approach showcased the development and validation of a combination therapy comprising a neuro-regenerative protective peptide hydrogel (SLNAP) and a potent neuro-regenerative chemical modulator (NCM). It is noteworthy to mention that this hydrogel formulation has injectable nature, which allows it to be applied at focal injury site of brain. Remarkably, our results reveal excellent transdifferentiation of human umbilical cord-derived mesenchymal stem cells (hMSCs) into functional neuron upon treatment with this combination therapeutic formulation. The functionality of regenerated neurons was thoroughly checked through observation of active signals generated from those neurons in electrophysiology recording using patch clamp. Further, we also observed that this strategy not only successfully converts hMSCs into neuron but also spontaneously formed neural stem cells (NSCs) like neurosphere. This work also showcased that this multidomain self-assembling peptide hydrogel emerges as an attractive soft-biomaterial due to its capability of slow and sustained release of the drug at the injury site upon topical application. This resulted in significant regeneration of functional neuron at the injury site. Fascinatingly, we found that this combination therapeutic strategy is highly effective in in vivo brain injury model establishing that this could be a potential and highly effective therapeutic strategy for TBI.