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Int. J. Mol. Sci. 2017, 18(8), 1705; doi:10.3390/ijms18081705

In Situ Forming Gelatin Hydrogels-Directed Angiogenic Differentiation and Activity of Patient-Derived Human Mesenchymal Stem Cells

1
Department of Biomedical Engineering, Vanderbilt University, Nasville, TN 37235, USA
2
Severance Biomedical Science Institute, College of Medicine, Yonsei University, Seoul 120-752, Korea
3
Department of Urology, College of Medicine, Yonsei University, Seoul 120-752, Korea
4
Department of Food Science and Biotechnology, College of Life Science, CHA University, Gyeonggi 443-742, Korea
5
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 July 2017 / Revised: 30 July 2017 / Accepted: 1 August 2017 / Published: 4 August 2017
(This article belongs to the Special Issue Novel Biomaterials for Tissue Engineering 2017)
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Abstract

Directing angiogenic differentiation of mesenchymal stem cells (MSCs) still remains challenging for successful tissue engineering. Without blood vessel formation, stem cell-based approaches are unable to fully regenerate damaged tissues due to limited support for cell viability and desired tissue/organ functionality. Herein, we report in situ cross-linkable gelatin−hydroxyphenyl propionic acid (GH) hydrogels that can induce pro-angiogenic profiles of MSCs via purely material-driven effects. This hydrogel directed endothelial differentiation of mouse and human patient-derived MSCs through integrin-mediated interactions at the cell-material interface, thereby promoting perfusable blood vessel formation in vitro and in vivo. The causative roles of specific integrin types (α1 and αvβ3) in directing endothelial differentiation were verified by blocking the integrin functions with chemical inhibitors. In addition, to verify the material-driven effect is not species-specific, we confirmed in vitro endothelial differentiation and in vivo blood vessel formation of patient-derived human MSCs by this hydrogel. These findings provide new insight into how purely material-driven effects can direct endothelial differentiation of MSCs, thereby promoting vascularization of scaffolds towards tissue engineering and regenerative medicine applications in humans. View Full-Text
Keywords: injectable gelatin hydrogels; patient-derived mesenchymal stem cells; integrin-mediated interactions; material-driven endothelial differentiation; angiogenesis injectable gelatin hydrogels; patient-derived mesenchymal stem cells; integrin-mediated interactions; material-driven endothelial differentiation; angiogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lee, Y.; Balikov, D.A.; Lee, J.B.; Lee, S.H.; Lee, S.H.; Lee, J.H.; Park, K.D.; Sung, H.-J. In Situ Forming Gelatin Hydrogels-Directed Angiogenic Differentiation and Activity of Patient-Derived Human Mesenchymal Stem Cells. Int. J. Mol. Sci. 2017, 18, 1705.

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