期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 48, 页码 41046-41055出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b13653
关键词
peptide amphiphile; human mesenchymal stem cell; IKVAV; transdifferentiation; neurons
资金
- Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern University
- Research Foundation-Flanders (FWO) [12G2718N]
- University of Leuven (KU Leuven) [JUMO-15-0514]
- Beatriu de Pinos Fellowship from Agencia de Gestio d'Ajust Universitaris i de Recerca, (AGAUR), Spain [2014 BP -A 00007]
- Paralyzed Veterans of America (PVA) Research Foundation [PVA17_RF_0008]
- U.S. Army Research Office
- U.S. Army Medical Research and Materiel Command
- Northwestern University
- Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [NSF ECCS-1542205, NSF NNCI-1542205]
- Materials Research Science and Engineering Center (MRSEC) program at the Materials Research Center [NSF DMR-1720139]
- International Institute for Nanotechnology (IIN)
- Keck Foundation
- State of Illinois, through the IIN
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 beta-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.
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