PMID- 34526090 OWN - NLM STAT- MEDLINE DCOM- 20220104 LR - 20220104 IS - 1757-2215 (Electronic) IS - 1757-2215 (Linking) VI - 14 IP - 1 DP - 2021 Sep 15 TI - Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice. PG - 119 LID - 10.1186/s13048-021-00871-4 [doi] LID - 119 AB - BACKGROUND: Currently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF. METHODS: Female mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy. RESULTS: Ovary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Mullerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin alpha, and inhibin beta was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group. CONCLUSION: These results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF. CI - (c) 2021. The Author(s). FAU - Lv, Xiaodan AU - Lv X AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. FAU - Guan, Chunyi AU - Guan C AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. FAU - Li, Ying AU - Li Y AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. FAU - Su, Xing AU - Su X AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. FAU - Zhang, Lu AU - Zhang L AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. FAU - Wang, Xueqin AU - Wang X AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. FAU - Xia, Hong-Fei AU - Xia HF AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. hongfeixia@126.com. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. hongfeixia@126.com. FAU - Ma, Xu AU - Ma X AD - Reproductive and Genetic Center of the National Research Institute for Family Planning, Beijing, 100081, China. genetic@263.net.cn. AD - Graduate School, Peking Union Medical College, Beijing, 100730, China. genetic@263.net.cn. LA - eng GR - No.81771590/National Natural Science Foundation of China/ GR - No. 2020GJZ02/National Research Institute for Family Planning/ GR - 3332020111/Special Funds for Fundamental Research Expenses of Central Universities/ PT - Journal Article DEP - 20210915 PL - England TA - J Ovarian Res JT - Journal of ovarian research JID - 101474849 SB - IM MH - Animals MH - Disease Models, Animal MH - Female MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - Ovarian Follicle/parasitology/pathology MH - Primary Ovarian Insufficiency/pathology/*therapy MH - Umbilical Cord/*cytology PMC - PMC8442267 OTO - NOTNLM OT - Ovarian function OT - Premature ovarian failure OT - Transplantation OT - hUC-MSCs COIS- The authors declare that they have no competing interests. EDAT- 2021/09/17 06:00 MHDA- 2022/01/05 06:00 PMCR- 2021/09/15 CRDT- 2021/09/16 05:47 PHST- 2021/01/12 00:00 [received] PHST- 2021/08/23 00:00 [accepted] PHST- 2021/09/16 05:47 [entrez] PHST- 2021/09/17 06:00 [pubmed] PHST- 2022/01/05 06:00 [medline] PHST- 2021/09/15 00:00 [pmc-release] AID - 10.1186/s13048-021-00871-4 [pii] AID - 871 [pii] AID - 10.1186/s13048-021-00871-4 [doi] PST - epublish SO - J Ovarian Res. 2021 Sep 15;14(1):119. doi: 10.1186/s13048-021-00871-4.