biostudies-literaturePei WNational Key R&amp;D Program of ChinaNational Key R&D Program of ChinaNational Natural Science Foundation of China96https://www.ebi.ac.uk/biostudies/studies/S-EPMC10988907biostudies-literatureUnknown15(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.Stem cell research & therapyEfficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.PMC109889078228810282192873822250192021YFC2700303Fan YGuo WFu LYang RLi RWang YPei WQiao JYu YfalseEfficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.2024-01-01T00:00:00Z2024 Apr2025-04-18T20:13:45.391Z2025-04-07T08:04:56.801ZS-EPMC109889073857089210.1186/s13287-024-03698-0