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Science China Life Sciences

, Volume 61, Issue 12, pp 1554–1565 | Cite as

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility

  • Lijun Ding
  • Guijun Yan
  • Bin Wang
  • Lu Xu
  • Yan Gu
  • Tong Ru
  • Xiaoying Cui
  • Lei Lei
  • Jingyu Liu
  • Xiaoqiang Sheng
  • Bin Wang
  • Chunxue Zhang
  • Yanjun Yang
  • Ruiwei Jiang
  • Jianjun Zhou
  • Na Kong
  • Feifei Lu
  • Huaijun Zhou
  • Yannan Zhao
  • Bing Chen
  • Yali HuEmail author
  • Jianwu DaiEmail author
  • Haixiang SunEmail author
Research Paper

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.

Keywords

premature ovarian failure collagen scaffold UC-MSCs primordial follicle activation granulosa cells FOXO3a FOXO1 

Notes

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).

Supplementary material

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Figure S1 AKT1 expression in ovaries co-cultured with collagen/UC-MSCs.
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Figure S2 Quantitative analyses of nuclear export of FOXO3a in oocytes of primordial follicles co-cultured with collagen/eSF or collagen/UC-MSCs.
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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.
11427_2017_9272_MOESM4_ESM.ai (5.9 mb)
Figure S4 The expression of Ki67 and C-caspase 3 in ovaries.
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Figure S5 An illustration of ovary co-cultured with collagen/UC-MSCs in a culture dish.
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Figure S6 Flow chart of the overall clinical study.
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Figure S7 GMP grade UC-MSCs documents.
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Figure S8 Procedure used for transplantation of collagen/UC-MSCs to ovaries of POF patients.
11427_2017_9272_MOESM9_ESM.docx (16 kb)
Table S1 Antibodies information Table S2 Primers sequences

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lijun Ding
    • 1
    • 2
  • Guijun Yan
    • 1
  • Bin Wang
    • 1
  • Lu Xu
    • 1
  • Yan Gu
    • 3
  • Tong Ru
    • 3
  • Xiaoying Cui
    • 1
  • Lei Lei
    • 1
  • Jingyu Liu
    • 1
  • Xiaoqiang Sheng
    • 1
  • Bin Wang
    • 2
  • Chunxue Zhang
    • 1
  • Yanjun Yang
    • 1
  • Ruiwei Jiang
    • 1
  • Jianjun Zhou
    • 1
  • Na Kong
    • 1
  • Feifei Lu
    • 1
  • Huaijun Zhou
    • 3
  • Yannan Zhao
    • 4
  • Bing Chen
    • 4
  • Yali Hu
    • 1
    Email author
  • Jianwu Dai
    • 4
    Email author
  • Haixiang Sun
    • 1
    Email author
  1. 1.Center for Reproductive Medicine, Department of Obstetrics and Gynecologythe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  2. 2.Clinical Center for Stem Cell Researchthe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  3. 3.Department of Obstetrics and Gynecologythe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
  4. 4.State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina

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