The therapeutic potential of bone marrow mesenchymal stem cells in premature ovarian failure

Yantao He, Dongmei Chen, Lingling Yang, Qiaoni Hou, Huiming Ma, Xian Xu, Yantao He, Dongmei Chen, Lingling Yang, Qiaoni Hou, Huiming Ma, Xian Xu

Abstract

With the development of regenerative medicine, a variety of mesenchymal stem cells (MSCs) are increasingly considered for the treatment of premature ovarian failure (POF). Reportedly, bone marrow-derived MSCs (BMSCs) improve the ovarian reserve, which mainly depends on homing and paracrine activities. Furthermore, paracrine factors secreted by these stem cells play an important role in ovarian recovery. Relevant studies indicate that BMSC transplantation has some positive effects on the treatment of POF in animals, but BMSCs are not widely applied in clinical therapy. Clinical trials are ongoing despite the fact that several patients experiencing BMSC transplantation recover their normal menstrual cycles and even give birth to babies. In this review, we discuss the possible therapeutic mechanisms of BMSCs for POF, migration, antiapoptosis, antifibrosis, angiogenesis, anti-inflammation, immunoregulation, and oxidative stress, which provide the theoretical basis for further study and clinical therapy.

Keywords: Bone marrow mesenchymal stem cells; Premature ovarian failure; Transplantation.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

We confirm the tables and figure in the manuscript are original for this article.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The possible mechanisms of bone marrow-derived mesenchymal stem cells (BMSCs). The migration of BMSCs is associated with CXCL8 and HGF. HGF, VEGF, IGF-1, TGF, bFGF, and GMCSF, secreted by BMSCs, contribute to inhibiting apoptosis. VEGF and HGF play an important role in angiogenesis. The mechanism of antioxidation is still unknown. ADM adrenomedullin, bFGF basic fibroblast growth factor, CXCL8 C-X-C chemokine ligand-8, GMCSF granulocyte macrophage colony-stimulating factor, HGF hepatocyte growth factor, HLAG5 human leukocyte antigen G5, IDO indoleamine 2,3-dioxygenase, IGF1 insulin-like growth factor-1, IL interleukin, iNOS inducible nitric oxide synthase, MCP1 monocyte chemoattractant protein 1, PGE2 prostaglandin E2, TGF transforming growth factor, TNF tumor necrosis factor, Treg regulatory T, VEGF vascular endothelial growth factor

References

    1. Nippita TA, Baber RJ. Premature ovarian failure: a review. Climacteric. 2007;10(1):11–22. doi: 10.1080/13697130601135672.
    1. Kovanci E, et al. Premature ovarian failure: clinical presentation and treatment. Obstet Gynecol Clin North Am. 2015;42(1):153–61. doi: 10.1016/j.ogc.2014.10.004.
    1. Cartwright B, et al. Hormone replacement therapy versus the combined oral contraceptive pill in premature ovarian failure: a randomized controlled trial of the effects on bone mineral density. J Clin Endocrinol Metab. 2016;101(9):3497–505. doi: 10.1210/jc.2015-4063.
    1. Liu J, et al. Homing and restorative effects of bone marrow-derived mesenchymal stem cells on cisplatin injured ovaries in rats. Molecules and Cells. 2014;37(12):865–72. doi: 10.14348/molcells.2014.0145.
    1. SA M, et al. Human mesenchymal stem cells partially reverse infertility in chemotherapy-induced ovarian failure. Reprod Sci. 2018;25(1):51–63.
    1. Guo J-Q, et al. BMSCs reduce rat granulosa cell optosis induced by cisplatin and perimenopause. BMC Cell Biol. 2013;14(1):1–9. doi: 10.1186/1471-2121-14-18.
    1. Edessy M, et al. Autologous stem cells therapy, the first baby of idiopathic premature ovarian failure. Acta Medica International. 2016;3(1):19–23. doi: 10.5530/ami.2016.1.7.
    1. Elkheir EAH. Autologous stem cell transplantation in patients with idiopathic premature ovarian failure. J Tissue Sci Eng. 10.4172/2157-7552.C1.030.
    1. Raeth S, et al. A mouse bone marrow stromal cell line with skeletal stem cell characteristics to study osteogenesis in vitro and in vivo. Stem Cells Dev. 2014;23(10):1097–108. doi: 10.1089/scd.2013.0367.
    1. Tsai S-C, Lu C-C. Stem cells prevent radiation exposure-induced ovarian follicular depletion. Biol Reprod. 2010;83(1):699. doi: 10.1093/biolreprod/83.s1.699.
    1. Gabr Hala, Rateb Moshira Abdelhakiim, El Sissy Maha Hamdi, Ahmed Seddiek Hanan., Ali Abdelhameed Gouda Sarah. The effect of bone marrow-derived mesenchymal stem cells on chemotherapy induced ovarian failure in albino rats. Microscopy Research and Technique. 2016;79(10):938–947. doi: 10.1002/jemt.22725.
    1. Ringe Jochen, Strassburg Sandra, Neumann Katja, Endres Michaela, Notter Michael, Burmester Gerd-Rüdiger, Kaps Christian, Sittinger Michael. Towards in situ tissue repair: Human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. Journal of Cellular Biochemistry. 2007;101(1):135–146. doi: 10.1002/jcb.21172.
    1. Sordi V. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood. 2005;106(2):419–427. doi: 10.1182/blood-2004-09-3507.
    1. CL, et al. MicroRNA-21 promotes bone mesenchymal stem cells migration in vitro by activating PI3K/Akt/MMPs pathway. J Clin Neurosci. 2017;46:156–162
    1. TK, et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004;94(5):678-685.
    1. Khanmohammadi N, et al. Effect of transplantation of bone marrow stromal cell- conditioned medium on ovarian function, morphology and cell death in cyclophosphamide-treated rats. Cell J. 2018;20(1):10–8.
    1. Fu X, et al. Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy. 2008;10(4):353–63. doi: 10.1080/14653240802035926.
    1. Shin S-Y, et al. Protective effect of vascular endothelial growth factor (VEGF) in frozen-thawed granulosa cells is mediated by inhibition of apoptosis. Eur J Obstet Gynecol Reprod Biol. 2006;125(2):233–8. doi: 10.1016/j.ejogrb.2005.10.027.
    1. Uzumcu M, et al. Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro. Reproduction. 2006;132(2):291–9. doi: 10.1530/rep.1.00989.
    1. Zhou P, Wu YG, Stocco C. IGF-1 signaling is required for FSH induction of Cyp19 expression in granulosa cells. Biol Reprod. 2012;87(1):609. doi: 10.1093/biolreprod/87.s1.609.
    1. Fu X, et al. Overexpression of miR-21 in stem cells improves ovarian structure and function in rats with chemotherapy-induced ovarian damage by targeting PDCD4 and PTEN to inhibit granulosa cell apoptosis. Stem Cell Res Ther. 2017;8(1):187. doi: 10.1186/s13287-017-0641-z.
    1. Figueroa FE, Carrión F, Villanueva S, Khoury M. Mesenchymal Stem Cell treatment for autoimmune diseases: a critical review Biol Res. 2012;45(3):269–77
    1. Yin N, et al. hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway. Stem Cell Res Ther. 2018;9(1):37. doi: 10.1186/s13287-018-0772-x.
    1. Afifi NM, Reyad ON. Role of mesenchymal stem cell therapy in restoring ovarian function in a rat model of chemotherapy-induced ovarian failure: a histological and immunohistochemical study. Egyptian J Histol. 2013;36(1):114–26. doi: 10.1097/01.EHX.0000423979.18253.10.
    1. Zhang Song-Ying, Zhou Feng, Shi Li-Bing. Ovarian Fibrosis: A Phenomenon of Concern. Chinese Medical Journal. 2017;130(3):365. doi: 10.4103/0366-6999.198931.
    1. Xia X, et al. Mesenchymal stem cells enhance angiogenesis and follicle survival in human cryopreserved ovarian cortex transplantation. Cell Transplant. 2015;24(10):1999–2000. doi: 10.3727/096368914X685267.
    1. Carrion BA, et al. Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their [alpha]6[beta]1 integrin receptor. Exp Cell Res. 2013;319(19):2964–76. doi: 10.1016/j.yexcr.2013.09.007.
    1. Maiborodin I, et al. Angiogenesis in rat uterine scar after introduction of autological mesenchymal stem cells of bone marrow origin. J Biomed Sci Eng. 2011;4(3):164–72. doi: 10.4236/jbise.2011.43023.
    1. Liang T, et al. Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling. FEBS Open Bio. 2017;7(11):1722–36. doi: 10.1002/2211-5463.12317.
    1. Zhang Y, Xia X, et al. Mesenchymal stem cell-derived angiogenin promotes primodial follicle survival and angiogenesis in transplanted human ovarian tissue. Reprod Biol Endocrinol. 2017;15(1):18.
    1. G-H S, et al. Hepatocyte growth factor gene-modified bone marrow-derived mesenchymal stem cells transplantation promotes angiogenesis in a rat model of hindlimb ischemia. J Huazhong Univ Sci Technol Med Sci. 2013;33(4):511–519.
    1. Meng S, Wong WT, Cooke J. LMO2 regulates angiogenesis through TGFB1 and HGF. FASEB J. 2015;29(1):796.
    1. Hoot KE, et al. HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion. J Clin Invest. 2013;123(3):1402. doi: 10.1172/JCI69077.
    1. Golocheikine Anjali, Tiriveedhi Venkataswarup, Angaswamy Nataraju, Benshoff Nicholas, Sabarinathan Ramachandran, Mohanakumar Thalachallour. Cooperative Signaling for Angiogenesis and Neovascularization by VEGF and HGF Following Islet Transplantation. Transplantation. 2010;90(7):725–731. doi: 10.1097/TP.0b013e3181ef8a63.
    1. Beilmann M, Birk G, Lenter MC. Human primary co-culture angiogenesis assay reveals additive stimulation and different angiogenic properties of VEGF and HGF. Cytokine. 2004;26(4):178–85. doi: 10.1016/j.cyto.2004.03.003.
    1. Kachgal S, et al. Bone marrow stromal cells stimulate an angiogenic program that requires endothelial MT1-MMP. J Cell Physiol. 2012;227(11):3546–55. doi: 10.1002/jcp.24056.
    1. Volkova Nataliia, Yukhta Mariia, Goltsev Anatoliy. Mesenchymal Stem Cells in Restoration of Fertility at Experimental Pelvic Inflammatory Disease. Stem Cells International. 2017;2017:1–9. doi: 10.1155/2017/2014132.
    1. Yin Na, Zhao Wei, Luo Qianqian, Yuan Wendan, Luan Xiying, Zhang Hongqin. Restoring Ovarian Function With Human Placenta-Derived Mesenchymal Stem Cells in Autoimmune-Induced Premature Ovarian Failure Mice Mediated by Treg Cells and Associated Cytokines. Reproductive Sciences. 2017;25(7):1073–1082. doi: 10.1177/1933719117732156.
    1. Zhang Q, et al. Human amniotic epithelial cells inhibit granulosa cell apoptosis induced by chemotherapy and restore the fertility. Stem Cell Res Ther. 2015;6(1):1–10. doi: 10.1186/scrt535.
    1. Zhang N, et al. GW25–e5365 Bone marrow stem cells: immune property genes assay and effect of transplantation on the immune cells of heart failure patients. J Am Coll Cardiol. 2014;64(16):C46. doi: 10.1016/j.jacc.2014.06.223.
    1. Németh K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42–9. doi: 10.1038/nm.1905.
    1. Zhao N, et al. Bone marrow-derived mesenchymal stem cells reduce immune reaction in a mouse model of allergic rhinitis. Am J Transl Res. 2016;8(12):5628–36.
    1. Hu J, et al. BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway. Am J Transl Res. 2017;9(1):79–89.
    1. Liang C, et al. Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro. Hematology. 2018;23(1):44–9. doi: 10.1080/10245332.2017.1333245.
    1. William TT, et al. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation. 2003;75(3):389–97. doi: 10.1097/01.TP.0000045055.63901.A9.
    1. Glennie S, et al. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. 2005;105(7):2821–7. doi: 10.1182/blood-2004-09-3696.
    1. Corcione A, et al. Human mesenchymal stem cells modulate B-cell functions. Blood. 2006;107(1):367–72. doi: 10.1182/blood-2005-07-2657.
    1. Bartholomew A, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42–8. doi: 10.1016/S0301-472X(01)00769-X.
    1. Di Nicola M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99(10):3838–43. doi: 10.1182/blood.V99.10.3838.
    1. Ebelt H, et al. Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines. Stem Cells. 2007;25(1):236–44. doi: 10.1634/stemcells.2006-0374.
    1. Wu Jingguo, Ji Chengbo, Cao Feifei, Lui Hongfen, Xia Bo, Wang Lanping. Bone marrow mesenchymal stem cells inhibit dendritic cells differentiation and maturation by microRNA-23b. Bioscience Reports. 2017;37(2):BSR20160436. doi: 10.1042/BSR20160436.
    1. Horton JA, et al. Mesenchymal stem cells inhibit cutaneous radiation-induced fibrosis by suppressing chronic inflammation. Stem Cells. 2013;31(10):2231–41. doi: 10.1002/stem.1483.
    1. E Kp; QH Cfjgtgpv; NC Gtu. The identity and properties of mesenchymal stem cells. .
    1. Kumar M, et al. Chromosomal abnormalities and oxidative stress in women with premature ovarian failure (POF) Indian J Med Res. 2012;135(1):92–7. doi: 10.4103/0971-5916.93430.
    1. Luderer U. Oxidative stress is a driver of normal and pathological ovarian aging. In: Inflammation, Aging Oxidative Stress; 2016. p. 213–37.
    1. Venkatesh S, et al. Oxidative stress and ATPase6 mutation is associated with primary ovarian insufficiency. Arch Gynecol Obstet. 2010;282(3):313–8. doi: 10.1007/s00404-010-1444-y.
    1. Xiang L, Ma H, et al. Human placental mesenchymal stem cell transplantation improves ovarian function by reducing the expression of superoxide dismutase 1 and coupling protein-2. Zhonghua Shengzhi Biyun. 2018;2:101–8. In Chinese.
    1. Sun T, et al. Bone marrow-derived mesenchymal stem cell transplantation ameliorates oxidative stress and restores intestinal mucosal permeability in chemically induced colitis in mice. Am J Transl Res. 2015;7(5):891–901.
    1. Tauchmanovà L, et al. Estrogen-progestin therapy in women after stem cell transplant: our experience and literature review. Menopause. 2007;14(2):320–30. doi: 10.1097/01.gme.0000232032.84788.8c.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する