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

Science Advances
Mi-Lan KangHak-Joon Sung

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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Citations

Dec 22, 2020·Frontiers in Cell and Developmental Biology·Ghada BeldiSina Naserian
Apr 16, 2021·Advanced Science·Grazia MarsicoAbhay Pandit

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
confocal microscopy
PCR
flow cytometry
ELISA
electrophoresis

Software Mentioned

GeneSpring
Image J
SPSS
Core Analysis in Ingenuity Pathways Analysis
Affymetrix GeneChip Command Console
ImageJ
ZEN

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