1. A comparative study of Mesenchymal Stem Cells transplantation approach to antagonize age-associated ovarian hypofunction with consideration of safety and efficiency
- Author
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Qiaojuan Mei, Ping Su, Wenpei Xiang, Huiying Li, Kezhen Li, Qin Xie, Jing Li, Lingjuan Wang, Ding Ma, Gang Chen, and Ling Zhang
- Subjects
Multidisciplinary ,TUNEL assay ,business.industry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Primary Ovarian Insufficiency ,Mesenchymal Stem Cell Transplantation ,medicine.disease ,Premature ovarian failure ,Andrology ,Transplantation ,Blot ,Mice ,Follicle ,Ovarian Follicle ,Apoptosis ,Animals ,Humans ,Medicine ,Female ,Ovarian Diseases ,Viability assay ,business - Abstract
Introduction The transplantation of mesenchymal stem cells (MSCs) in patients with premature ovarian failure (POF) could lead to clinical improvement. The transplantation to the ovaries among other transplantation methods have been reported in various animal models, however, there is little evidence regarding the optimal method, including the clinical safety and the efficiency for the treatment of age associated ovarian hypofunction. Objectives To establish the most effective transplantation route of MSCs, explore the resistance to therapy, its safety and role in the natural aging process of the ovaries. Methods Highly purified MSCs were injected intraperitoneally, directly into the ovaries or tail-intravenously in mice animal model. The ovarian function, quantity and quality of oocytes, cell viability/apoptosis, were evaluated, applying chemiluminescence analysis (CLIA), western blotting, immunofluorescence staining, transmission electron microscope (TEM), TdT mediated dUTP Nick End Labeling (TUNEL) assay and other techniques. The organ tumorigenicity was also evaluated by long-term observation and histopathological examination. The efficiency of MSCs was further verified in non-human primates by the most effective transplantation route. Results The 32nd week was ultimately determined as the time point of MSCs transplantation. Our results showed that the intra-ovarian injection was the best transplantation method with a more conspicuous effect. With deeper investigations, we found that the transplanted MSCs showed an effective influence on the follicular number, promoted follicle maturation and inhibited cell apoptosis, which was further verified in non-human primates. In addition, the long-term observation and the histopathological examinations ruled out neoplasms or obvious prosoplasia after MSCs transplantation. Conclusion MSCs transplantation by intra-ovarian injection could within a month exert the most conspicuous anti-age-associated ovarian hypofunction effects, which may improve the quantity and quality of oocytes by changing the mitochondrial structure, regulating mitochondrial function and attenuating cell apoptosis to increase the storage of the follicle pool without a remarkable potential of tumorigenicity.
- Published
- 2022