Bioactive Nanofibers Induce Neural Transdifferentiation of Human Bone Marrow Mesenchymal Stem Cells

Abstract

The combination of biomaterials with stem cells is a promising therapeutic strategy to repair traumatic injuries in the central nervous system, and human bone marrow mesenchymal stem cells (BMSCs) offer a clinically translatable option among other possible sources of stem cells. We report here on the use of a supramolecular bioactive material based on a peptide amphiphile (PA), displaying a laminin-mimetic IKVAV sequence to drive neural transdifferentiation of human BMSCs. The IKVAV-PA self-assembles into supramolecular nanofibers that induce neuroectodermal lineage commitment after 1 week, as evidenced by the upregulation of the neural progenitor gene nestin ( NES) and glial fibrillary acidic protein ( GFAP). After 2 weeks, the bioactive IKVAV-PA nanofibers induce significantly higher expression of neuronal markers β-III tubulin (TUJ-1), microtubule-associated protein-2 (MAP-2), and neuronal nuclei (NEUN), as well as the extracellular matrix laminin (LMN). Furthermore, the human BMSCs exposed to the biomaterial reveal a polarized cytoskeletal architecture and a decrease in cellular size, resembling neuron-like cells. We conclude that the investigated supramolecular biomaterial opens the opportunity to transdifferentiate adult human BMSCs into neuronal lineage.