Abstract
Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.
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Acknowledgements
The authors would like to thank Xiaoling Sun, Yong Liu and Fangfang He for their technical assistance in TVUS-guided transplantation, flow cytometry and repeated transvaginal ultrasonographic examinations, respectively. This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030501 to Haixiang Sun), National Natural Science Foundation of China (31571189, 81571391, 30900847 to Lijun Ding), Jiangsu Provincial Medical Youth Talent (QNRC2016006) and Nanjing Medical Science Development Project (JQX14004, ZKX16042).
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Figure S1
AKT1 expression in ovaries co-cultured with collagen/UC-MSCs.
Figure S2
Quantitative analyses of nuclear export of FOXO3a in oocytes of primordial follicles co-cultured with collagen/eSF or collagen/UC-MSCs.
Figure S3
Treatment with collagen/UC-MSCs had no effect on the expression of p-AKT1, FOXO3a and p-FOXO1 at 48 h. A—J, The expression of p-AKT1, FOXO3a and p-FOXO1 was determined using IHC.
Figure S4
The expression of Ki67 and C-caspase 3 in ovaries.
Figure S5
An illustration of ovary co-cultured with collagen/UC-MSCs in a culture dish.
Figure S6
Flow chart of the overall clinical study.
Figure S7
GMP grade UC-MSCs documents.
Figure S8
Procedure used for transplantation of collagen/UC-MSCs to ovaries of POF patients.
Table S1
Antibodies information
Table S2 Primers sequences
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Ding, L., Yan, G., Wang, B. et al. Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility. Sci. China Life Sci. 61, 1554–1565 (2018). https://doi.org/10.1007/s11427-017-9272-2
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DOI: https://doi.org/10.1007/s11427-017-9272-2