Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing, 100191, China.
Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, 100191, China.
Stem Cell Res Ther. 2024 Apr 3;15(1):96. doi: 10.1186/s13287-024-03698-0.
Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified.
Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved.
After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function.
Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.
卵巢衰老系影响女性生育力的主要问题之一。近年来，间充质干细胞（MSC）疗法取得了令人瞩目的进展。然而，作为非自体成分的 MSC 的疗效和安全性仍有待进一步验证。
将两种常见的 MSC 来源（脐带间充质干细胞[UC-MSCs]和脂肪组织来源的间充质干细胞[AD-MSCs]）原位移植到卵巢衰老的小鼠模型中，以评估其治疗效果。进一步评估治疗的安全性，并进行 RNA 测序以探讨所涉及的潜在机制。
将 MSC 原位移植到卵巢后，发情周期、卵巢重量、初级卵泡数量和比例、颗粒细胞增殖和血管生成得到改善。AD-MSCs 在移植后颗粒细胞增殖、卵巢重量和血管生成等多个指标上的效果优于 UC-MSCs。此外，评估了 MSC 的致瘤性、急性毒性、免疫原性和生物分布，发现 AD-MSCs 和 UC-MSCs 均具有较高的安全性。通过 RNA 测序分析，观察到 MAPK 级联的增强，而长期效应主要与免疫功能的激活有关。
MSC 的原位移植对治疗小鼠卵巢衰老具有显著疗效和高度安全性。
