BMSCs May Assist in the Treatment of Premature Ovarian Failure in Cancer Patients | Stemodontics®
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BMSCs May Assist in the Treatment of Premature Ovarian Failure in Cancer Patients

Exosomes, small particles made by bone marrow mesenchymal stem cells, may be useful in treating ovarian failure induced by cancer therapy.

ABSTRACT

Bone marrow mesenchymal stem cell-derived exosomal miR-144-5p improves rat ovarian function after chemotherapy-induced ovarian failure by targeting PTEN.

Lab Invest. 2019 Sep 19. doi: 10.1038/s41374-019-0321-y. [Epub ahead of print]

Yang M1,2, Lin L1,2, Sha C1,2, Li T1,2, Zhao D2, Wei H1, Chen Q1, Liu Y1, Chen X2, Xu W3,4, Li Y5, Zhu X6,7.

Author information

  1. Reproductive Sciences Institute, Jiangsu University, Zhenjiang, 212003, Jiangsu, China.
  2. Department of Gynecologic Oncology and Central Laboratory, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China.
  3. Reproductive Sciences Institute, Jiangsu University, Zhenjiang, 212003, Jiangsu, China. [email protected].
  4. Department of Gynecologic Oncology and Central Laboratory, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China. [email protected].
  5. Department of Oncology, Affiliated People Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China. [email protected].
  6. Reproductive Sciences Institute, Jiangsu University, Zhenjiang, 212003, Jiangsu, China. [email protected].
  7. Department of Gynecologic Oncology and Central Laboratory, Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China. [email protected].

Abstract

Chemotherapy-induced premature ovarian failure (POF) in women is currently clinically irreversible. Bone marrow mesenchymal stem cells (BMSCs) are a promising cellular therapeutic strategy for POF. However, the underlying mechanism governing the efficacy of BMSCs in treating POF has not been determined. In this study, we show that BMSC and BMSC-derived exosome transplantation can significantly recover the estrus cycle, increase the number of basal and sinus follicles in POF rats, increase estradiol (E2) and anti-Mullerian hormone (AMH) levels, and reduce follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in the serum. Furthermore, we demonstrate that BMSC-derived exosomes prevent ovarian follicular atresia in cyclophosphamide (CTX)-treated rats via the delivery of miR-144-5p, which can be transferred to cocultured CTX-damaged granulosa cells (GCs) to decrease GC apoptosis. A functional assay revealed that overexpression of miR-144-5p in BMSCs showed efficacy against CTX-induced POF, and the improvement in the repair was related to the inhibition of GC apoptosis by targeting PTEN. The opposite effect was exhibited when miR-144-5p was inhibited. Taken together, our experimental results provide new information regarding the potential of using exosomal miR-144-5p to treat ovarian failure.

 

PMID:31537899

DOI:10.1038/s41374-019-0321-y