TY - JOUR
T1 - Bioactive Nanofibers Induce Neural Transdifferentiation of Human Bone Marrow Mesenchymal Stem Cells
AU - Ji, Wei
AU - Álvarez, Zaida
AU - Edelbrock, Alexandra N.
AU - Sato, Kohei
AU - Stupp, Samuel I.
N1 - Funding Information:
This work was primarily supported by the Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern University. W.J. received postdoctoral support from Research FoundationFlanders (FWO) Postdoctoral Mandates 12G2718N, and by a Junior Mobility Travel grant from University of Leuven (KU Leuven) (JUMO-15-0514). Z.Á. received postdoctoral support from a Beatriu de Pinoś Fellowship from Ageǹcia de Gestió d’Ajust Universitaris i de Recerca, (AGAUR), Spain 2014 BP-A 00007, and by grant #PVA17_RF_0008 from the Paralyzed Veterans of America (PVA) Research Foundation. This work was also supported by the following core facilities of Northwestern University: the Peptide Synthesis Core and the Analytical Bionanotechnology Equipment Core both at the Simpson Querrey Institute. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop these facilities and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205). This work made use of the microscopic facility of the Center for Advanced Microscopy (NCI CCSG P30 CA060553), as well as the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the Materials Research Science and Engineering Center (MRSEC) program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. The authors also thank Max Mu Wang’s technical assistance and Mark Seniw for the preparation of illustrations for the manuscript.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/12/5
Y1 - 2018/12/5
N2 - 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.
AB - 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.
KW - IKVAV
KW - human mesenchymal stem cell
KW - neurons
KW - peptide amphiphile
KW - transdifferentiation
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U2 - 10.1021/acsami.8b13653
DO - 10.1021/acsami.8b13653
M3 - Article
C2 - 30475573
AN - SCOPUS:85058093131
VL - 10
SP - 41046
EP - 41055
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
SN - 1944-8244
IS - 48
ER -