Open AccessExogenous Signaling Molecules Released from Aptamer-Functionalized Hydrogels Promote the Survival of Mesenchymal Stem Cell Spheroids
Author(s) -
Nan Zhao,
James Coyne,
Lidya Abune,
Peng Shi,
Xiaojun Lian,
Ge Zhang,
Yong Wang
Publication year - 2020
Publication title -
acs applied materials and interfaces
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.535
H-Index - 228
eISSN - 1944-8252
pISSN - 1944-8244
DOI - 10.1021/acsami.0c05681
Subject(s) - mesenchymal stem cell , self healing hydrogels , in vivo , microbiology and biotechnology , platelet derived growth factor receptor , spheroid , vascular endothelial growth factor , growth factor , in vitro , aptamer , platelet derived growth factor , biology , chemistry , cancer research , vegf receptors , biochemistry , receptor , organic chemistry
Mesenchymal stem cells (MSCs) have a very low survival rate after in vivo delivery, which limits their great promise for treating human diseases. Various strategies have been studied to overcome this challenge. However, an overlooked but important potential is to apply exogenous signaling molecules as biochemical cues to promote MSC survival, presumably because it is well-known that MSCs themselves can release a variety of potent signaling molecules. Thus, the purpose of this work was to examine and understand whether the release of exogenous signaling molecules from hydrogels can promote the survival of MSC spheroids. Our data show that more vascular endothelial growth factor (VEGF) but not platelet-derived growth factor BB (PDGF-BB) were released from MSC spheroids in comparison with 2D cultured MSCs. Aptamer-functionalized fibrin hydrogel (aFn) could release exogenous VEGF and PDGF-BB in a sustained manner. PDGF-BB-loaded aFn promoted MSC survival by ∼70% more than VEGF-loaded aFn under the hypoxic condition in vitro. Importantly, PDGF-BB-loaded aFn could double the survival rate of MSC spheroids in comparison with VEGF-loaded aFn during the one-week test in vivo. Therefore, this work demonstrated that defined exogenous signaling molecules (e.g., PDGF-BB) can function as biochemical cues for promoting the survival of MSC spheroids in vivo.