Free radical biology & medicineApr 27, 2024

Human umbilical cord stem cells may reduce chemotherapy-caused early ovarian failure in mice by stopping iron-related cell death in ovarian support cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can protect ovarian granulosa cells from chemotherapy-induced cell death.

Primary ovarian insufficiency (POI) in younger women is characterized by irregular periods, high follicle-stimulating hormone (FSH), and low estradiol (E2).
Cyclophosphamide (CTX) induces ferroptosis in ovarian granulosa cells, contributing to POI.
hUC-MSC treatment mitigates the effects of CTX-induced ferroptosis in ovarian granulosa cells in both living organisms and controlled environments.
hUC-MSCs may suppress ferroptosis by activating a protective antioxidant pathway in granulosa cells through NRF2, a regulator of stress responses.
Findings suggest that hUC-MSCs could enhance ovarian function in cases of CTX-induced POI by reducing cell death.

Simplified

Primary ovarian insufficiency (POI) in younger women (under 40) manifests as irregular periods, high follicle-stimulating hormone (FSH), and low estradiol (E2), often triggered by chemotherapy. Though mesenchymal stem cell (MSC) therapy shows promise in treating POI, its exact mechanism remains unclear. This study reveals that human umbilical cord-derived MSCs (hUC-MSCs) can protect ovarian granulosa cells (GCs) from cyclophosphamide (CTX)-induced ferroptosis, a form of cell death driven by iron accumulation. CTX, commonly used to induce POI animal model, triggered ferroptosis in GCs, while hUC-MSCs treatment mitigated this effect, both in vivo and in vitro. Further investigations using ferroptosis and autophagy inhibitors suggest that hUC-MSCs act by suppressing ferroptosis in GCs. Interestingly, hUC-MSCs activate a protective antioxidant pathway in GCs via NRF2, a stress-response regulator. Overall, our findings suggest that hUC-MSCs improve ovarian function in CTX-induced POI by reducing ferroptosis in GCs. This study not only clarifies the mechanism behind the benefits of hUC-MSCs but also strengthens the case for their clinical use in treating POI. Additionally, it opens up a new avenue for protecting ovaries from chemotherapy-induced damage by regulating ferroptosis.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Human umbilical cord stem cells may reduce chemotherapy-caused early ovarian failure in mice by stopping iron-related cell death in ovarian support cells

Abstract

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Competing interests

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