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Hydrogel cross-linking–programmed release of nitric oxide regulates source-dependent angiogenic behaviors of human mesenchymal stem cell

Authors
Kang, Mi-LanKim, Hye-SeonYou, JinChoi, Young SikKwon, Byeong-JuPark, Chan HeeBaek, WooyeolKim, Min SupLee, Yong JaeIm, Gun-IlYoon, Jeong-KeeLee, Jung BokSung, Hak-Joon
Issue Date
Feb-2020
Publisher
American Association for the Advancement of Science
Keywords
BONE-MARROW; PERICYTES; PROMOTES; TISSUE; ENDOTHELIUM; EXPRESSION; PHENOTYPE; SYSTEM
Citation
Science Advances, v.6, no.9
Journal Title
Science Advances
Volume
6
Number
9
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146879
DOI
10.1126/sciadv.aay5413
ISSN
2375-2548
2375-2548
Abstract
Angiogenesis is stimulated by nitric oxide (NO) production in endothelial cells (ECs). Although proangiogenic actions of human mesenchymal stem cells (hMSCs) have been extensively studied, the mechanistic role of NO in this action remains obscure. Here, we used a gelatin hydrogel that releases NO upon crosslinking by a transglutaminase reaction (“NO gel”). Then, the source-specific behaviors of bone marrow versus adipose tissue-derived hMSCs (BMSCs versus ADSCs) were monitored in the NO gels. NO inhibition resulted in significant decreases in their angiogenic activities. The NO gel induced pericyte-like characteristics in BMSCs in contrast to EC differentiation in ADSCs, as evidenced by tube stabilization versus tube formation, 3D colocalization versus 2D coformation with EC tube networks, pericyte-like wound healing versus EC-like vasculogenesis in gel plugs, and pericyte versus EC marker production. These results provide previously unidentified insights into the effects of NO in regulating hMSC source-specific angiogenic mechanisms and their therapeutic applications.
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