Dataset Information

Mechanism of 17-β Estradiol Stimulated Integration of Human Mesenchymal Stem Cells in Heart Tissue

ABSTRACT: Scarcity of gender specific donor hearts highlights the importance of mesenchymal stem cells (MSCs) as a therapeutic tool for heart repair. However, inefficient incorporation, retention, and activity of MSCs in cardiac tissue remains an obstacle. Since surge in follicular estradiol (μmolar-range) triggers tissue remodeling (e.g. ovulation) and estradiol exerts beneficial actions on the cardiovascular system, we hypothesized that estradiol may promote/improve MSC-mediated cardiac repair processes. Methods: Wharton’s jelly-derived MSCs were used, to assess the effects of estradiol on their proliferation, directed-migration and engraftment in murine heart slices, ex vivo. Results: MSCs expressed estrogen receptors (ERs) α and β, and estradiol promoted MSC proliferation (measured using xCELLigence real-time cell-impedance system and DNA-quantification). Estradiol up-regulated mRNA (qRT-PCR) and protein expression (western blotting) of ERα, ERβ, EMMPRIN, and MMP-9, yet down-regulated MMP-2 expression. In MSCs estradiol, up-regulated mRNA expression of VEGF-A, VCAM-1, and angiogenin, and stimulated NO production via ER. Proteomic analysis revealed that in MSCs estradiol up-regulated 47 proteins, down-regulated 7 proteins, and increased the expression of key biochemical components/pathways involved in tissue repair. In MSCs co-cultured with murine heart-slices, estradiol significantly induced MSC migration in an ER-dependent fashion (and preferentially via ERα) and significantly increased the secretion of MMP-2, MMP-9, angiogenin and VEGF. Conclusion: Estradiol facilitates the integration/engraftment of MSCs into heart slices by promoting MSC proliferation and migration and these beneficial effects are mediated via increases in molecules/pathways involved in tissue remodeling and angiogenesis. Priming of MSCs with estradiol may enhance their ability to repair/regenerate cardiac tissue in women.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Heart Disease

SUBMITTER: Felicia Antohe

LAB HEAD: Felicia Antohe

PROVIDER: PXD011742 | Pride | 2019-06-24

REPOSITORIES: Pride

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Mechanism of 17β-estradiol stimulated integration of human mesenchymal stem cells in heart tissue.

Mihai Maria Cristina MC Popa Mirel Adrian MA Suica Viorel Iulian VI Antohe Felicia F Jackson Edwin K EK Simionescu Maya M Dubey Raghvendra K RK

Journal of molecular and cellular cardiology 20190613

Scarcity of gender specific donor hearts highlights the importance of mesenchymal stem cells (MSCs) as a therapeutic tool for heart repair. However, inefficient incorporation, retention, and activity of MSCs in cardiac tissue remain an obstacle. Since surges in follicular estradiol (E2; μmolar-range) trigger tissue remodeling (e.g. ovulation) and E2 exerts beneficial actions on the cardiovascular system, we hypothesized that E2 may promote/improve MSC-mediated cardiac repair processes. Using Wha ...[more]

PMID: 31201797

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