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.
| Original language | English |
|---|---|
| Pages (from-to) | 41046-41055 |
| Number of pages | 10 |
| Journal | ACS Applied Materials and Interfaces |
| Volume | 10 |
| Issue number | 48 |
| DOIs | |
| Publication status | Published - Dec 5 2018 |
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Keywords
- human mesenchymal stem cell
- IKVAV
- neurons
- peptide amphiphile
- transdifferentiation
ASJC Scopus subject areas
- Materials Science(all)
Cite this
Bioactive Nanofibers Induce Neural Transdifferentiation of Human Bone Marrow Mesenchymal Stem Cells. / Ji, Wei; Álvarez, Zaida; Edelbrock, Alexandra N.; Sato, Kohei; Stupp, Samuel I.
In: ACS Applied Materials and Interfaces, Vol. 10, No. 48, 05.12.2018, p. 41046-41055.Research output: Contribution to journal › Article
}
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
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 - human mesenchymal stem cell
KW - IKVAV
KW - neurons
KW - peptide amphiphile
KW - transdifferentiation
UR - http://www.scopus.com/inward/record.url?scp=85058093131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058093131&partnerID=8YFLogxK
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 -