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Updated: May 28, 2026
Isolation of Adipose Derived Regenerative Cells for the Treatment of Erectile Dysfunction Following Radical Prostatectomy
Published on: December 28, 2021
Estrogen Enhances Endothelial Differentiation and Angiogenic Function of Adipose-Derived Stromal Cells to Improve
Hsin-Ju Chiang1,2, Chang-Chun Hsiao1,3, Steve Leu4,5,6
1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan.
Background:
Aging, especially after menopause, reduces the quantity and function of adult stem cells. Estrogen deficiency impairs proliferation, differentiation, and regenerative capacity. This study evaluated whether estrogen enhances endothelial differentiation of adipose-derived stromal cells (ADSCs) and improves therapeutic efficacy in critical limb ischemia (CLI).
Methods:
Male-derived ADSCs were assessed in vitro for endothelial differentiation using flow cytometry, biochemical assays, and angiogenesis analyses. Therapeutic effects were tested in a rat CLI model using endothelial-differentiated ADSCs (ED-ADSCs) with or without 17β-estradiol (E2). An ovariectomized (OVX) model examined estrogen deficiency and supplementation in vivo.
Results:
E2 promoted endothelial differentiation, increasing ERα/ERβ expression and activating PI3K/Akt/eNOS and MAPK signaling. This led to elevated VEGF expression, enhanced tube formation, and increased CD34+, KDR+, and CD31+ cell populations. In vivo, E2-pretreated ED-ADSCs significantly improved blood flow recovery. Estrogen deficiency reduced endothelial progenitor populations, which were restored by E2 supplementation.
Conclusions:
Estrogen modulates endothelial-associated characteristics and angiogenesis-related responses of ADSCs via ER-associated signaling, and may contribute to improved functional outcomes in ischemic conditions. E2 preconditioning may represent a potential strategy for stem cell-based therapy in estrogen-deficient settings.
