Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP‐Mediated Mechanosensing
Abstract
Stem cells secrete trophic factors that induce angiogenesis. These soluble factors are promising candidates for stem cell–based therapies, especially for cardiovascular diseases. Mechanical stimuli and biophysical factors presented in the stem cell microenvironment play important roles in guiding their behaviors. However, the complex interplay and precise role of these cues in directing pro‐angiogenic signaling remain unclear. Here, a platform is designed using gelatin methacryloyl hydrogels with tunable rigidity and a dynamic mechanical compression bioreactor to evaluate the influence of matrix rigidity and mechanical stimuli on the secretion of pro‐angiogenic factors from human mesenchymal stem cells (hMSCs). Cells cultured in matrices mimicking mechanical elasticity of bone tissues in vivo show elevated secretion of vascular endothelial growth factor (VEGF), one of representative signaling proteins promoting angiogenesis, as well as increased vascularization of human umbilical vein endothelial cells (HUVECs) with a supplement of conditioned media from hMSCs cultured across different conditions. When hMSCs are cultured in matrices stimulated with a range of cyclic compressions, increased VEGF secretion is observed with increasing mechanical strains, which is also in line with the enhanced tubulogenesis of HUVECs. Moreover, it is demonstrated that matrix stiffness and cyclic compression modulate secretion of pro‐angiogenic molecules from hMSCs through yes‐associated protein activity.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 17, 2020
- Source ID
- 10.1002/smll.202001837
Entities
People
- Ali Khademhosseini
- Fereshteh Vajhadin
- Giorgia Cefaloni
- Han‐jun Kim
- Hyun‐jong Cho
- Junmin Lee
- Kangju Lee
- Marcus J. Goudie
- Martin C. Hartel
- Mehmet Remzi Dökmeci
- Praveen Bandaru
- Samad Ahadian
- Shiming Zhang
- Wujin Sun
Organizations
- Kangwon National University
- National Institutes of Health
- Office of the Secretary of Defense
- UCLA Henry Samueli School of Engineering and Applied Science
- University of California, Los Angeles
- University of Yazd