Reconstructive approaches to treating secondary infertility

DOI

https://dx.doi.org/10.18565/aig.2021.2.32-38

Pulver A.Yu., Pulver N.A., Poltavtseva R.A.
1) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) Institute of Biology of Aging LLC, Voronezh, Russia; 3) Voronezh City Emergency Clinical Hospital No 10, Voronezh, Russia

Secondary infertility is one of the most pressing health problems often resulting from endometrial injury after abortions or complicated delivery, as well as in hormonal dysregulation, Asherman’s syndrome (AS) is the most severe form, in which there are uterine synechiae, the adhesions connecting the opposite uterine walls, which complicates a normal menstrual process. Existing approaches can help some women with AS become pregnant and carry a baby, but the efficiency of therapy remains relatively low, which requires further investigation. The review considers new promising approaches to treating AS, by using tissue engineering, cell technologies, and biologically active substances. Tissue engineering techniques can contribute to the restoration of one's own tissue or organ. The body is able to regenerate damaged tissue in the presence of the matrix that is the supporting framework for the functional cells of the endometrium in the event of damage to the cells of the uterus. When designing the biomaterials that promote the restoration of damaged tissue, the thing that matters is a material and the latter’s incorporated biologically active components with regenerative activity. The biomaterials should ensure mechanical support for tissue repair, partially mimicking the natural environment through the metered release of extracellular vesicles, growth factors, and other signaling molecules. The review gives data on the efficiency of using the populations of stem cells and progenitor cells derived from bone marrow, endometrium, and umbilical cord Wharton’s jelly for the treatment of endometrial diseases.

endometrium

secondary infertility

tissue engineering

cell therapy

multipotent mesenchymal stromal cells

Ascherman’s syndrome

angiogenesis

Full text (in Russian)

Denisov B.P., Sakevich V.I., Jasilioniene A. Divergent trends in abortion and birth control practices in Belarus, Russia and Ukraine. PLoS One. 2012; 7(11): e49986. https://dx.doi.org/10.1371/journal.pone.0049986.
Panayotidis C., Weyers S., Bosteels J., Herendael B. Intrauterine adhesions (IUA): has there been progress in understanding and treatment over the last 20 years? Gynecol. Surg. 2009; 6: 197-211. https://dx.doi.org/10.1007/s10397-008-0421-y.
Gargett C.E., Ye L. Endometrial reconstruction from stem cells. Fertil. Steril. 2012; 98(1): 11-20. https://dx.doi.org/10.1016/j.fertnstert.2012.05.004.
Malhotra N., Bahadur A., Kalaivani M., Mittal S. Changes in endometrial receptivity in women with Asherman's syndrome undergoing hysteroscopic adhesiolysis. Arch. Gynecol. Obstet. 2012; 286(2): 525-30. https://dx.doi.org/10.1007/s00404-012-2336-0.
Takagi S., Shimizu T., Kuramoto G., Ishitani K., Matsui H., Yamato M. et al. Reconstruction of functional endometrium-like tissue in vitro and in vivo using сеll sheet engineering. Biochem. Biophys. Res. Commun. 2014; 446(1): 335-40. https://dx.doi.org/10.1016/j.bbrc.2014.02.107.
Kuramoto G., Takagi S., Ishitani K., Shimizu T., Okano T., Matsui H. Preventive effect of oral mucosal epithelial cell sheets on intrauterine adhesions. Hum. Reprod. 2015; 30(2): 406-16. https://dx.doi.org/10.1093/humrep/deu326.
Li X., Sun H., Lin N., Hou X., Wang J., Zhou B. et al. Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor. Biomaterials. 2011; 32(32): 8172-81. https://dx.doi.org/10.1016/j.biomaterials.2011.07.050.
Cao Y., Sun H., Zhu H., Zhu X., Tang X., Yan G. et al. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial. Stem Cell Res. Ther. 2018; 9(1): 192. https://dx.doi.org/10.1186/s13287-018-0904-3.
Cervelló I., Gil-Sanchis C., Santamaría X., Cabanillas S., Díaz A., Faus A. et al. Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome. Fertil. Steril. 2015; 104(6): 1552-60. e1-3. https://dx.doi.org/10.1016/j.fertnstert.2015.08.032.
Gan L., Duan H., Xu Q., Tang Y.Q., Li J.J., Sun F.Q. et al. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions. Cytotherapy. 2017; 19(5): 603-16. https://dx.doi.org/10.1016/j.jcyt.2017.02.003.
Xu L., Ding L., Wang L., Cao Y., Zhu H., Lu J. et al. Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP-9 in rat uterine scars. Stem Cell Res. Ther. 2017; 8(1): 84. https://dx.doi.org/10.1186/s13287-017-0535-0.
Santamaria X., Cabanillas S., Cervelló I., Arbona C., Raga F., Ferro J. et al. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study. Hum. Reprod. 2016; 31(5): 1087-96. https://dx.doi.org/10.1093/humrep/dew042.
Gronthos S., Fitter S., Diamond P., Simmons P.J., Itescu S., Zannettino A.C. A novel monoclonal antibody (STRO-3) identifies an isoform of tissue nonspecific alkaline phosphatase expressed by multipotent bone marrow stromal stem cells. Stem Cells Dev. 2007; 16(6): 953-63. https://dx.doi.org/10.1089/scd.2007.0069.
Monsef F., Artimani T., Alizadeh Z., Ramazani M., Solgi G., Yavangi M. et al. Comparison of the regenerative effects of bone marrow/adipose-derived stem cells in the Asherman model following local or systemic administration. J. Assist. Reprod. Genet. 2020; 37(8): 1861-8. https://dx.doi.org/10.1007/s10815-020-01856-w.
Gao L., Huang Z., Lin H., Tian Y., Li P., Lin S. Bone marrow mesenchymal stem cells (BMSCs) restore functional endometrium in the rat model for severe Asherman syndrome. Reprod. Sci. 2019; 26(3): 436-44. https://dx.doi.org/10.1177/1933719118799201.
Golle L., Gerth H.U., Beul K., Heitplatz B., Barth P., Fobker M. et al. Bone marrow-derived cells and their conditioned medium induce microvascular repair in uremic rats by stimulation of endogenous repair mechanisms. Sci. Rep. 2017; 7(1): 9444. https://dx.doi.org/10.1038/s41598-017-09883-x.
Kovina M.V., Krasheninnikov M.E., Dyuzheva T.G., Danilevsky M.I., Klabukov I.D., Balyasin M.V. et al. Human endometrial stem cells: High-yield isolation and characterization. Cytotherapy. 2018; 20(3): 361-74. https://dx.doi.org/10.1016/j.jcyt.2017.12.012.
Chan R.W., Schwab K.E., Gargett C.E. Clonogenicity of human endometrial epithelial and stromal cells. Biol. Reprod. 2004; 70(6): 1738-50. https://dx.doi.org/10.1095/biolreprod.103.024109.
Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4): 315-7. https://dx.doi.org/10.1080/14653240600855905.
Gargett C.E., Schwab K.E., Deane J.A. Endometrial stem/progenitor cells: the first 10 years. Hum. Reprod. Update. 2016; 22(2): 137-63. https://dx.doi.org/10.1093/humupd/dmv051.
Tan J., Li P., Wang Q., Li Y., Li X., Zhao D. et al. Autologous menstrual blood-derived stromal cells transplantation for severe Asherman's syndrome. Hum. Reprod. 2016; 31(12): 2723-9. https://dx.doi.org/10.1093/humrep/dew235.
Saribas G.S., Ozogul C., Tiryaki M., Alpaslan Pinarli F., Hamdemir Kilic S. Effects of uterus derived mesenchymal stem cells and their exosomes on asherman's syndrome. Acta Histochem. 2020; 122(1): 151465. https://dx.doi.org/10.1016/j.acthis.2019.151465.
Klemmt P.A.B., Starzinski-Powitz A. Molecular and cellular pathogenesis of endometriosis. Curr. Womens Health Rev. 2018; 14(2): 106-16. https://dx.doi.org/10.2174/1573404813666170306163448.
von Bahr L., Batsis I., Moll G., Hägg M., Szakos A., Sundberg B. et al. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells. 2012; 30(7): 1575-8. https://dx.doi.org/10.1002/stem.1118.
Li B., Zhang Q., Sun J., Lai D. Human amniotic epithelial cells improve fertility in an intrauterine adhesion mouse model. Stem Cell Res. Ther. 2019; 10(1): 257. https://dx.doi.org/10.1186/s13287-019-1368-9.
Singh N., Mohanty S., Seth T., Shankar M., Bhaskaran S., Dharmendra S. Autologous stem cell transplantation in refractory Asherman's syndrome: A novel cell based therapy. J. Hum. Reprod. Sci. 2014; 7(2): 93-8. https://dx.doi.org/10.4103/0974-1208.138864.
Liu Y., Tal R., Pluchino N., Mamillapalli R., Taylor H.S. Systemic administration of.bone marrow-derived cells leads to better uterine engraftment than use of utrine-derived cells or local injection. J. Cell. Mol. Med. 2018; 22(1): 67-76. https://dx.doi.org/10.1111/jcmm.13294.
Сухих Г.Т., Чернуха Г.Е., Табеева Г.И., Горюнов К.В., Силачев Д.Н. Современные возможности клеточной терапии синдрома Ашермана. Акушерство и гинекология. 2018; 5: 20-8. [Sukhikh G.T., Chernukha G.E., Tabeeva G.I., Goryunov K.V., Silachev D.N. Current possibilities of cell therapy for Asherman’s syndrome. Obstetrics and Gynecology. 2018; 5: 20-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.5.20-28.
Körbling M., Anderlini P. Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter? Blood. 2001; 98(10): 2900-8. https://dx.doi.org/10.1182/blood.v98.10.2900.
Sun K., Zhou Z., Ju X., Zhou Y., Lan J., Chen D. et al. Combined transplantation of mesenchymal stem cells and endothelial progenitor cells for tissue engineering: a systematic review and meta-analysis. Stem Cell Res. Ther. 2016; 7(1): 151. https://dx.doi.org/10.1186/s13287-016-0390-4.
Nagori C.B., Panchal S.Y., Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman's syndrome. J. Hum. Reprod. Sci. 2011; 4(1): 43-8. https://dx.doi.org/10.4103/0974-1208.82360.
Singh N., Mohanty S., Seth T., Shankar M., Bhaskaran S., Dharmendra S. Autologous stem cell transplantation in refractory Asherman's syndrome: A novel cell based therapy. J. Hum. Reprod. Sci. 2014; 7(2): 93-8. https://dx.doi.org/10.4103/0974-1208.138864.
Yang M., Lin L., Sha C., Li T., Zhao D., Wei H. et al. Bone marrow mesenchymal stem cell-derived exosomal miR-144-5p improves rat ovarian function after chemotherapy-induced ovarian failure by targeting PTEN. Lab. Invest. 2020; 100(3): 342-52. https://dx.doi.org/10.1038/s41374-019-0321-y.
Ng Y.H., Rome S., Jalabert A., Forterre A., Singh H., Hincks C.L. et al. Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation. PLoS One. 2013; 8(3): e58502. https://dx.doi.org/10.1371/journal.pone.0058502.
Almiñana C., Corbin E., Tsikis G., Alcântara-Neto A.S., Labas V., Reynaud K. et al. Oviduct extracellular vesicles protein content and their role during oviduct-embryo cross-talk. Reproduction. 2017; 154(3): 153-68. https://dx.doi.org/10.1530/REP-17-0054.
Reliszko Z.P., Gajewski Z., Kaczmarek M.M. Signs of embryo-maternal communication: miRNAs in the maternal serum of pregnant pigs. Reproduction. 2017; 154(3): 217-28. https://dx.doi.org/10.1530/REP-17-0224.
Álvarez V., Sánchez-Margallo F.M., Macías-García B., Gómez-Serrano M., Jorge I., Vázquez J. et al. The immunomodulatory activity of extracellular vesicles derived from endometrial mesenchymal stem cells on CD4+ T cells is partially mediated by TGFbeta. J. Tissue Eng. Regen. Med. 2018; 12(10): 2088-98. https://dx.doi.org/10.1002/term.2743.
Blázquez R., Sánchez-Margallo F.M., Álvarez V., Matilla E., Hernández N., Marinaro F. et al. Murine embryos exposed to human endometrial MSCs-derived extracellular vesicles exhibit higher VEGF/PDGF AA release, increased blastomere count and hatching rates. PLoS One. 2018; 13(4): e0196080. https://dx.doi.org/10.1371/journal.pone.0196080.
Poltavtseva R.A., Poltavtsev A.V., Lutsenko G.V., Svirshchevskaya E.V. Myths, reality and future of mesenchymal stem cell therapy. Cell Tissue Res. 2019; 375(3): 563-74. https://dx.doi.org/10.1007/s00441-018-2961-4.
de Witte S.F.H., Luk F., Sierra Parraga J.M., Gargesha M., Merino A., Korevaar S.S. et al. Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells. Stem Cells. 2018; 36(4): 602-15. https://dx.doi.org/10.1002/stem.2779.
Galleu A., Riffo-Vasquez Y., Trento C., Lomas C., Dolcetti L., Cheung T.S. et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci. Transl. Med. 2017; 9(416): eaam7828. https://dx.doi.org/10.1126/scitranslmed.aam7828.
Chang Y., Li J., Chen Y., Wei L., Yang X., Shi Y. et al. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int. J. Clin. Exp. Med. 2015; 8(1):1286-90.
Zadehmodarres S., Salehpour S., Saharkhiz N., Nazari L. Treatment of thin endometrium with autologous platelet-rich plasma: a pilot study. JBRA Assist. Reprod. 2017; 21(1): 54-6. https://dx.doi.org/10.5935/1518-0557.20170013.
Chang Y., Li J., Wei L.N., Pang J., Chen J., Liang X. Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium. Medicine (Baltimore). 2019; 98(3): e14062. https://dx.doi.org/10.1097/MD.0000000000014062.
Эфендиева З.Н., Аполихина И.А., Калинина Е.А., Федорова Т.А., Бакуридзе Э.М., Белоусов Д.М., Фатхудинов Т.Х., Сухих Г.Т. Первый опыт инъекционного введения аутологичной плазмы, обогащенной тромбоцитами, в эндометрий пациенток с маточным фактором бесплодия. Акушерство и гинекология. 2020; 4: 82-9. [Efendieva Z.N., Apolikhina I.А., Kalinina Е.А., Fedorova Т.А., Bakuridze E.М., Belousov D.М., Fathudinov Т.Kh., Sukhikh G.Т. First experience of autologous platelet rich plasma injection into the endometrium in patients with uterine factor infertility. Obstetrics and Gynecology. 2020; 4: 82-9. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.4.82-89.
Middleton K.K., Barro V., Muller B., Terada S., Fu F.H. Evaluation of the effects of platelet-rich plasma (PRP) therapy involved in the healing of sports-related soft tissue injuries. Iowa Orthop. J. 2012; 32: 150-63.
Piccoli S., Mehta D., Vitaliti A., Allinson J., Amur S., Eck S. et al. 2019 White Paper on Recent Issues in Bioanalysis: FDA immunogenicity guidance, gene therapy, critical reagents, biomarkers and flow cytometry validation (Part 3 – Recommendations on 2019 FDA immunogenicity guidance, gene therapy bioanalytical challenges, strategies for critical reagent management, biomarker assay validation, flow cytometry validation & CLSI H62). Bioanalysis. 2019; 11(24): 2207-44. https://dx.doi.org/10.4155/bio-2019-0271.
Hara A., Sato D., Sahara Y. New governmental regulatory system for stem cell-based therapies in Japan. Ther. Innov. Regul. Sci. 2014; 48(6): 681-8. https://dx.doi.org/10.1177/2168479014526877.

Received 27.06.2020

Accepted 16.02.2021

Alexander Yu. Pulver, operating surgeon, senior researcher of the Laboratory of Clinical Immunology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; General Director, Head of Laboratory, Institute of Biology of Aging LLC. Tel.: +7(903)655-88-80. E-mail: pulver.ibs@gmail.com. 4, Oparin str., Moscow, 117997, Russia.
Natalia A. Pulver, PhD (Med. Sci.), general physician, occupational pathologist, Head of the Admission Department, Voronezh City Clinical Emergency Hospital No. 10; senior researcher of the Laboratory of Clinical Immunology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. Tel.: +7(910)344-34-80. E-mail: elektronika10@yandex.ru. 4, Oparin str., Moscow, 117997, Russia.
Rimma A. Poltavtseva, PhD, leading researcher of the Laboratory of Clinical Immunology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. Tel.: +7(495)438-26-01. E-mail: rimpol@mail.ru; r_poltavtseva@oparina4.ru.
4, Oparin str., Moscow, 117997, Russia.

For citation: Pulver A.Yu., Pulver N.A., Poltavtseva R.A. Reconstructive approaches to treating secondary infertility.
Akusherstvo i Ginekologiya/ Obstetrics and Gynecology. 2021; 2: 32-38 (in Russian)
https://dx.doi.org/10.18565/aig.2021.2.32-38

Reconstructive approaches to treating secondary infertility

Pulver A.Yu., Pulver N.A., Poltavtseva R.A.

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