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

TitleMechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP-Mediated Mechanosensing
Authors
Keywordsvascular endothelial growth factor (VEGF)
yes-associated protein (YAP)
human mesenchymal stem cells (hMSCs)
dynamic compression bioreactors
angiogenesis
Issue Date2020
Citation
Small, 2020, v. 16, n. 25, article no. 2001837 How to Cite?
Abstract© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 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.
Persistent Identifierhttp://hdl.handle.net/10722/295431
ISSN
2023 Impact Factor: 13.0
2023 SCImago Journal Rankings: 3.348
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBandaru, Praveen-
dc.contributor.authorCefaloni, Giorgia-
dc.contributor.authorVajhadin, Fereshteh-
dc.contributor.authorLee, Kang Ju-
dc.contributor.authorKim, Han Jun-
dc.contributor.authorCho, Hyun Jong-
dc.contributor.authorHartel, Martin C.-
dc.contributor.authorZhang, Shiming-
dc.contributor.authorSun, Wujin-
dc.contributor.authorGoudie, Marcus J.-
dc.contributor.authorAhadian, Samad-
dc.contributor.authorDokmeci, Mehmet Remzi-
dc.contributor.authorLee, Junmin-
dc.contributor.authorKhademhosseini, Ali-
dc.date.accessioned2021-01-18T15:46:51Z-
dc.date.available2021-01-18T15:46:51Z-
dc.date.issued2020-
dc.identifier.citationSmall, 2020, v. 16, n. 25, article no. 2001837-
dc.identifier.issn1613-6810-
dc.identifier.urihttp://hdl.handle.net/10722/295431-
dc.description.abstract© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 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.-
dc.languageeng-
dc.relation.ispartofSmall-
dc.subjectvascular endothelial growth factor (VEGF)-
dc.subjectyes-associated protein (YAP)-
dc.subjecthuman mesenchymal stem cells (hMSCs)-
dc.subjectdynamic compression bioreactors-
dc.subjectangiogenesis-
dc.titleMechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP-Mediated Mechanosensing-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/smll.202001837-
dc.identifier.pmid32419312-
dc.identifier.pmcidPMC7523466-
dc.identifier.scopuseid_2-s2.0-85084700582-
dc.identifier.volume16-
dc.identifier.issue25-
dc.identifier.spagearticle no. 2001837-
dc.identifier.epagearticle no. 2001837-
dc.identifier.eissn1613-6829-
dc.identifier.isiWOS:000533243400001-
dc.identifier.issnl1613-6810-

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