2. Academic Validation
  3. Umbilical cord mesenchymal stem cells and their extracellular vesicles attenuate cryopreservation-induced ovarian injury via the suppression of ferroptosis in an in vitro culture system

Umbilical cord mesenchymal stem cells and their extracellular vesicles attenuate cryopreservation-induced ovarian injury via the suppression of ferroptosis in an in vitro culture system

  • Mater Today Bio. 2026 Feb 23:37:102965. doi: 10.1016/j.mtbio.2026.102965.
Wenjuan Xu 1 2 3,  Xiang Yao 1 2 3,  Chen Chen 4,  Mengyao Wang 1 2 3,  Yaxin Chen 1 2 3,  Dan Liang 1 2 3,  Qun Gao 4,  Xianwen Wang 5,  Ping Zhou 1 2 3,  Jianye Wang 1 2 3
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui, 230022, PR China.
  • 2 Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, No. 81 Meishan Road, Hefei, 230032, PR China.
  • 3 NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No. 81 Meishan Road, Hefei, Anhui, 230032, PR China.
  • 4 Department of Surgical Oncology, Anhui Provincial Children's Hospital, No.39 East Wangjiang Road, Hefei, Anhui, 230022, PR China.
  • 5 School of Biomedical Engineering, Anhui Medical University, Hefei, 230032, PR China.
PMID: 41800454 DOI: 10.1016/j.mtbio.2026.102965
Abstract

Ovarian tissue cryopreservation is a vital fertility preservation technique. However, cryopreservation-induced injury significantly limits its efficacy in frozen-thawed ovarian tissue transplantation. This study investigated the therapeutic potential of umbilical cord mesenchymal stem cells (UC-MSCs) and their derived extracellular vesicles (MSC-EVs) for repairing cryopreservation-induced ovarian injury via Ferroptosis in an in vitro culture system. RNA Sequencing revealed Ferroptosis as a key regulatory pathway in cryopreserved ovarian tissue. This was characterized by downregulation of GPX4, upregulation of ACSL4, elevated Fe2+ levels, glutathione depletion, and enhanced lipid peroxidation. UC-MSCs and MSC-EVs effectively suppressed Ferroptosis, restored GPX4 expression, and reduced lipid peroxidation, mirroring the effects of the Ferroptosis inhibitor ferrostatin-1. In an in vitro culture system, UC-MSCs and MSC-EVs enhanced follicular survival and angiogenesis, while reducing Apoptosis. Transplantation experiments demonstrated improved graft vascularization, hormone secretion, and oocyte retrieval in treated groups. Notably, MSC-EVs demonstrated comparable efficacy to UC-MSCs, suggesting their potential as a nanoscale therapeutic strategy. These findings elucidate Ferroptosis as a critical mechanism in cryopreservation-induced injury and highlight UC-MSCs and MSC-EVs as promising therapeutic agents for improving ovarian tissue cryopreservation outcomes.

Keywords

Extracellular vesicles; Ferroptosis; Mesenchymal stem cells; Ovarian tissue cryopreservation; Ovarian tissue transplantation.

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