Optimization of Microenvironments Inducing Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Endothelial Cell-Like Cells
10.1007/s13770-019-00221-y
- Author:
Se Young OH
1
;
Da Hyeon CHOI
;
Yoon Mi JIN
;
Yeonsil YU
;
Ha Yeong KIM
;
Gyungah KIM
;
Yoon Shin PARK
;
Inho JO
Author Information
1. Department of Molecular Medicine, College of Medicine, Ewha Womans University, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, Republic of Korea. inhojo@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
Tonsils;
Mesenchymal stem cells;
Endothelial cells;
Differentiation;
Microenvironments
- MeSH:
Blood Vessels;
Blotting, Western;
Eagles;
Endothelial Cells;
Fluorescent Antibody Technique;
Gelatin;
Genome;
Human Umbilical Vein Endothelial Cells;
Mesenchymal Stromal Cells;
Morphogenesis;
Nitric Oxide Synthase Type III;
Palatine Tonsil;
Real-Time Polymerase Chain Reaction;
Serine;
Stem Cells
- From:
Tissue Engineering and Regenerative Medicine
2019;16(6):631-643
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments.METHODS: TMSCs were preconditioned with Dulbecco's Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers.RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells.CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.