hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice

Yue Xiao; Yue Peng; Chi Zhang; Wei Liu; Kehan Wang; Jing Li

doi:10.7555/JBR.36.20220166

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Yue Xiao, Yue Peng, Chi Zhang, Wei Liu, Kehan Wang, Jing Li. hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.36.20220166

Citation:

Yue Xiao, Yue Peng, Chi Zhang, Wei Liu, Kehan Wang, Jing Li. hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.36.20220166

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hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice

doi: 10.7555/JBR.36.20220166

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China

Funds: This work is supported by National Key Research and Development Program of China (Grants No. 2018YFC1003703 and 2018YFC1004203,) and National Natural Science Foundation of China (31871513).

More Information

Corresponding author: Jing Li, Room B101, Xuehai Building, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 210029, China. Tel: 025-86869504 , E-mail: ljwth@njmu.edu.cn
Received: 2022-07-25
Revised: 2022-08-28
Accepted: 2022-09-04

Published: 2022-11-10

Abstract

Abstract

Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to chemotherapy drugs like cisplatin. Various methods have been explored for fertility preservation in women, especially in prepubertal girls undergoing radiotherapy and chemotherapy because of cancer. In recent years, mesenchymal stem cell-derived exosomes (MSC-exos) have been reported to play an important role in tissue repair and treatment of various diseases. In this study, by using exosomes human umbilical cord-derived from mesenchymal stem cells, we observed that human umbilical cord-derived MSC-exos (hucMSC-exos) after short-term culture improved follicular survival and development while receiving cisplatin treatment. Moreover, the intravenous injection of hucMSC-exos improved ovarian function and ameliorated the inflammatory environment within the ovary. The underlying mechanism of hucMSC-exos on fertility preservation was associated with the down-regulation of p53-related apoptosis and their anti-inflammatory function. Taken together, we proposed that HucMSC-derived exosomes might be a potential approach to improve fertility in women diagnosed with cancer.
- ovarian function,
- ovarian reserve,
- cisplatin,
- exosomes,
- apoptosis

CLC number: R711.75; R730.53, Document code: A
The authors reported no conflict of interests.

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References(27)

References

[1]	Miller III JJ, Williams GF, Leissring JC. Multiple late complications of therapy with cyclophosphamide, including ovarian destruction[J]. Am J Med, 1971, 50(4): 530–535. doi: 10.1016/0002-9343(71)90341-X
[2]	Jayasinghe YL, Wallace WHB, Anderson RA. Ovarian function, fertility and reproductive lifespan in cancer patients[J]. Expert Rev Endocrinol Metab, 2018, 13(3): 125–136. doi: 10.1080/17446651.2018.1455498
[3]	Ho GY, Woodward N, Coward JIG. Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies[J]. Crit Rev Oncol Hematol, 2016, 102: 37–46. doi: 10.1016/j.critrevonc.2016.03.014
[4]	Jamieson ER, Lippard SJ. Structure, recognition, and processing of cisplatin-DNA adducts[J]. Chem Rev, 1999, 99(9): 2467–2498. doi: 10.1021/cr980421n
[5]	Spears N, Lopes F, Stefansdottir A, et al. Ovarian damage from chemotherapy and current approaches to its protection[J]. Hum Reprod Update, 2019, 25(6): 673–693. doi: 10.1093/humupd/dmz027
[6]	Yang Y, Zhao Y, Liao W, et al. Acetylation of FoxO1 activates Bim expression to induce apoptosis in response to histone deacetylase inhibitor depsipeptide treatment[J]. Neoplasia, 2009, 11(4): 313–324. doi: 10.1593/neo.81358
[7]	Maidarti M, Anderson RA, Telfer EE. Crosstalk between PTEN/PI3K/Akt signalling and DNA damage in the oocyte: implications for primordial follicle activation, oocyte quality and ageing[J]. Cells, 2020, 9(1): 200. doi: 10.3390/cells9010200
[8]	Ding D, Chang Y, Shyu WC, et al. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy[J]. Cell Transplant, 2015, 24(3): 339–347. doi: 10.3727/096368915X686841
[9]	Shareghi-Oskoue O, Aghebati-Maleki L, Yousefi M. Transplantation of human umbilical cord mesenchymal stem cells to treat premature ovarian failure. Stem Cell Res Ther[J]. Stem Cell Res Ther , 2021, 12(1): 454. doi: 10.1186/s13287-021-02529-w. doi: 10.1186/s13287-021-02529-w
[10]	Yang W, Zhang J, Xu B, et al. HucMSC-derived exosomes mitigate the age-related retardation of fertility in female mice[J]. Mol Ther, 2020, 28(4): 1200–1213. doi: 10.1016/j.ymthe.2020.02.003
[11]	He C, Zheng S, Luo Y, Wang B, et al. Exosome Theranostics: Biology and Translational Medicine. Theranostics, 2018, 8(1): 237-255. doi: 10.7150/thno.21945
[12]	Lopes F, Liu J, Morgan S, et al. Single and combined effects of cisplatin and doxorubicin on the human and mouse ovary in vitro. Reproduction, 2020, 159(2): 193-204. doi: 10.1530/REP-19-0279
[13]	Digby JLM, Vanichapol T, Przepiorski A, et al. Evaluation of cisplatin-induced injury in human kidney organoids. Am J Physiol Renal Physiol, 2020;318(4): F971-F978. doi: 10.1152/ajprenal.00597.2019
[14]	Freedman BS, Brooks CR, Lam AQ, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids[J]. Nat Commun, 2015, 6: 8715. doi: 10.1038/ncomms9715
[15]	Edlich F. BCL-2 proteins and apoptosis: Recent insights and unknowns[J]. Biochem Biophys Res Commun, 2018, 500(1): 26–34. doi: 10.1016/j.bbrc.2017.06.190
[16]	Domingo IK, Latif A, Bhavsar AP. Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity. Int J Mol Sci, 2022;23(13): 7227. doi: 10.3390/ijms23137227
[17]	Morita Y, Perez GI, Paris F, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy[J]. Nat Med, 2000, 6(10): 1109–1114. doi: 10.1038/80442
[18]	Nguyen QN, Zerafa N, Liew SH, et al. Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility[J]. Cell Death Dis, 2018, 9(6): 618. doi: 10.1038/s41419-018-0633-7
[19]	Bildik G, Akin N, Senbabaoglu F, et al. GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro[J]. Hum Reprod, 2015, 30(12): 2912–2925. doi: 10.1093/humrep/dev257
[20]	Hirata Y, Takahashi M, Yamada Y, et al. trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway[J]. Sci Rep, 2021, 11(1): 10350. doi: 10.1038/s41598-021-89506-8
[21]	Yuksel A, Bildik G, Senbabaoglu F, et al. The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells[J]. Hum Reprod, 2015, 30(12): 2926–2935. doi: 10.1093/humrep/dev256
[22]	2014 2014 175247
[23]	Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis[J]. J Transl Med, 2015, 13: 49. doi: 10.1186/s12967-015-0417-0
[24]	Zhang B, Wang M, Gong AH, et al. HucMSC-exosome mediated-Wnt4 signaling is required for cutaneous wound healing[J]. Stem Cells, 2015, 33(7): 2158–2168. doi: 10.1002/stem.1771
[25]	Li T, Xia M, Gao Y, et al. Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy[J]. Expert Opin Biol Ther, 2015, 15(9): 1293–1306. doi: 10.1517/14712598.2015.1051528
[26]	Ling L, Feng X, Wei T, et al. Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism[J]. Stem Cell Res Ther, 2019, 10(1): 46. doi: 10.1186/s13287-019-1136-x
[27]	Rani S, Ryan AE, Griffin MD, et al. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications[J]. Mol Ther, 2015, 23(5): 812–823. doi: 10.1038/mt.2015.44