Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms18081705
Keywords
injectable gelatin hydrogels; patient-derived mesenchymal stem cells; integrin-mediated interactions; material-driven endothelial differentiation; angiogenesis
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2016M3A9E9941743, NRF-2015R1A2A1A14027221]
- National Research Foundation of Korea [2016M3A9E9941743] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 ((1) and (v3)) 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.
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