2. Academic Validation
  3. Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP-Mediated Mechanosensing

Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP-Mediated Mechanosensing

  • Small. 2020 Jun;16(25):e2001837. doi: 10.1002/smll.202001837.
Praveen Bandaru 1 2,  Giorgia Cefaloni 1 2,  Fereshteh Vajhadin 1 2 3,  KangJu Lee 1 2,  Han-Jun Kim 1 2,  Hyun-Jong Cho 1 2 4,  Martin C Hartel 1 2,  Shiming Zhang 1 2,  Wujin Sun 1 2,  Marcus J Goudie 1 2,  Samad Ahadian 1 2 5,  Mehmet Remzi Dokmeci 2 5 6,  Junmin Lee 1 2,  Ali Khademhosseini 1 2 5 6 7
Affiliations

Affiliations

  • 1 Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • 2 Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • 3 Department of Chemistry, Faculty of Science, Yazd University, Yazd, 89195-741, Iran.
  • 4 College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
  • 5 Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90064, USA.
  • 6 Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
  • 7 Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
PMID: 32419312 DOI: 10.1002/smll.202001837
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.

Keywords

angiogenesis; dynamic compression bioreactors; human mesenchymal stem cells (hMSCs); vascular endothelial growth factor (VEGF); yes-associated protein (YAP).

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