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
  • 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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