Bioengineering the ovary to preserve and reestablish female fertility
Fulvio Gandolfi, Matteo Ghiringhelli, Tiziana A.L. Brevini
Abstract
Different bioengineering strategies can be presently adopted and have been shown to have great potential in the treatment of female infertility and ovarian dysfunction deriving from chemotherapy, congenital malformations, massive adhesions as well as aging and lifestyle. One option is transplantation of fresh or cryopreserved organs/fragments into the patient. A further possibility uses tissue engineering approaches that involve a combination of cells, biomaterials and factors that stimulate local ability to regenerate/ repair the reproductive organ. Organ transplant has shown promising results in large animal models. However, the source of the organ needs to be identified and the immunogenic effects of allografts remain still to be solved before the technology may enter the clinical practice. Decellularization/ repopulation of ovary with autologous cells or follicles could represent an interesting, still very experimental alternative. Here we summarize the recent advancements in the bioengineering strategies applied to the ovary, we present the principles for these systems and discuss the advantages of these emerging opportunities to preserve or improve female fertility.
Keywords
References
Anderson RA, Wallace WH. 2011. Fertility preservation in girls and young women. Clin Endocrinol (Oxf), 75:409-419.
Andrée B, Bela K, Horvath T, Lux M, Ramm R, Venturini L, Ciubotaru A, Zweigerdt R, Haverich A, Hilfiker A. 2014. Successful re-endothelialization of a perfusable biological vascularized matrix (BioVaM) for the generation of 3D artificial cardiac tissue. Basic Res Cardiol, 109:1-13.
Bromer JG, Patrizio P. 2009. Fertility preservation: the rationale for cryopreservation of the whole ovary. Semin Reprod Med, 27:465-471.
Che-Ying K, Avinash E, Jesse KP, Kelly RR, Helim AE, Rohan F, John PF, Peter CW. 2016. Development of a 3D printed, bioengineered placenta model to evaluate the role of trophoblast migration in preeclampsia. ACS Biomater Sci Eng, 2(10):1817-1826.
Chung K, Donnez J, Ginsburg E, Meirow D. 2013. Emergency IVF versus ovarian tissue cryopreservation: decision making in fertility preservation for female cancer patients. Fertil Steril, 99:1534-1542.
Dolmans MM, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J. 2010. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood, 116:2908-2914.
Donnez J, Dolmans MM, Pellicer A, Diaz-Garcia C, Sanchez Serrano M, Schmidt KT, Ernst E, Luyckx V, Andersen CY. 2013. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril, 99:1503-1513.
Edson MA, Nagaraja AK, Matzuk MM. 2009. The mammalian ovary from genesis to revelation. Endocr Rev, 30: 624-712.
Ghiringhelli M, Zenobi A, Brizzola S, Gandolfi F, Bontempo V, Rossi S, Brevini TAL, Acocella F. 2017. Simple and quick method to obtain a decellularized, fuctional liver bioscaffold. Methods Mol Bio,
Gilbert TW, Sellaro TL, Badylak SF. 2006. Decellularization of tissues and organs. Bio-materials, 27:3675-3683.
Greve T, Clasen-Linde E, Andersen MT, Andersen MK, Sorensen SD, Rosendahl M, Ralfkiaer E, Andersen CY. 2012. Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells. Blood, 120:4311-4316.
Hewlett M, Mahalingaiah S. 2015. Update on primary ovarian insufficiency. Curr Opin Endocrinol Diab Obes, 22(6):483-489.
Hinderer S, Schenke-Layland K. 2013. Tracheal tissue engineering: building on a strong foundation, Expert Rev Med Devices, 10:33-35.
Hinderer S, Layland SL, Schenke-Layland K. 2016. ECM and ECM-like materials – Biomaterials for applications in regenerative medicine and cancer therapy. Adv Drug Deliv Rev, 97:260-269
Huet C, Pisselet C, Mandon-Pepin B, Monget P, Monniaux D. 2001. Extracellular matrix regulates ovine granulosa cell survival, proliferation and steroidogenesis: relationships between cell shape and function. J Endocrinol, 169(2):347-60.
Irvine SA, Agrawal A., Lee BH, Chua HY, Low KY, Lau BC, Machulf M, Venkatraman S. 2015. Printing cell-laden gelatin constructs by free-form fabrication and enzymatic protein crosslinking. Biomed Microdevices, 17:16-18.
Keane TJ, Swinehart IT, Badylak SF. 2015. Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance. Methods, 84:25-34.
Kreeger PK, Woodruff TK, Shea LD. 2003. Murine granulosa cell morphology and function are regulated by a synthetic Arg-Gly-Asp matrix. Mol Cell Endocrinol, 205(1-2):1-10.
Kreeger PK, Deck JW, Woodruff TK, Shea LD. 2006.The in vitro regulation of ovarian follicle development using alginate-extracellular matrix gels. Biomaterials, 27(5):714-723.
Krotz SP, Robins JC, Ferruccio TM, Moore R, Steinhoff MM, Morgan JR, Carson S. 2010. In vitro maturation of oocytes via the prefabricated self-assembled artificial human ovary. J Assist Reprod Genet, 27(12):743-750.
Laronda MM, Jakus AE, Whelan KA, Wertheim JA, Shah RN, Woodruff TK. 2015. Initiation of puberty in mice following decellularized ovary transplant. Biomaterials, 50:20-29.
Larsen E, Loft A, Holm K, Muller J, Brocks V, Andersen AN. 2000. Oocyte donation in women cured of cancer with bone marrow transplantation including
total body irradiation in adolescence. Hum Reprod, 15(7):1505-1508.
Lenie S, Cortvrindt R, Eichenlaub-Ritter U, Smitz J. 2008 Continuous exposure to bisphenol A during in vitro follicular development induces meiotic abnormalities. Mutat Res, 651:71-81.
Maffei S, Pennarossa G, Brevini TA, Arav A, Gandolfi F. 2014. Beneficial effect of directional freezing on in vitro viability of cryopreserved sheep whole ovaries and ovarian cortical slices. Hum Reprud, 29(1):114-124.
Maffei S, Galeati G, Pennarossa G, Brevini TAL, Gandolfi F. 2015. Extended ex vivo culture of fresh and cryopreserved whole sheep ovaries. Reproduction, Fertility and Development, 28(12):1893-1903.
Meirow D, Hardan I, Dor J, Fridman E, Elizur S, Ra'anani H, Slyusarevsky E, Amariglio N, Schiff E, Rechavi G, Nagler A, Ben Yehuda D. 2008. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod, 23:1007-1013.
Oktay K, Karlikaya G, Akman O, Ojakian GK, Oktay M. 2000. Interaction of extracellular matrix and activin-A in the initiation of follicle growth in the mouse ovary. Biol Reprod, 63:457-461.
Oktay K, Bedoschi G, Pacheco F, Turan V, Emirdar V. 2016. First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery. Am J Obstet Gynecol, 214:94. e1-94.e9.
Oktem O, Oktay K. 2007. The role of extra-cellular matrix and activin-A in in vitro growth and survival of murine preantral follicles. Reprod Sci, 14:358-366.
Pangas SA, Saudye H, Shea LD, Woodruff TK. 2003. Novel approach for the three-dimensional culture of granulosa cell-oocyte complexes. Tissue Eng, 9(5):1013-21.
Pati F, Jang J, Ha DH, Kim SW, Rhie JW, Shim JH, Kim DH, Cho DW. 2014. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink, Nat Commun, 5:3935.
Paulose T, Tannenbaum LV, Borgeest C, Flaws JA. 2012. Methoxychlor-induced ovarian follicle toxicity in mice: dose and exposure duration-dependent effects. Birth Defects Res B Dev Reprod Toxicol, 2012; 95:219-224.
Picton HM, Harris SE, Muruvi W, Chambers EL. 2008. The in vitro growth and maturation of follicles. Reproduction, 136:703-715.
Qin YY, Jiao X, Simpson JL, Chen ZJ. 2015. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update, 21(6):787-808.
Rodriguez-Wallberg K, Karlstrom PO, Rezapour M, Castellanos E, Hreinsson J, Rasmussen, Sheikhi M, Ouvrier B, Bozoky B, Olofsson JI, Lundgvist M, Hovatta O. 2015. Full-term newborn after repeated ovarian tissue transplants in a patient treated for Ewing sarcoma by sterilizing pelvic irradiation and chemotherapy. Acta Obstet Gynecol Scand, 94(3):324-8.
Sadri-Ardekani H, Atala A. 2015. Regenerative medicine for the treatment of reproductive system disorders: current and potential options. Adv Drug Deliv Rev, 82:45-158.
Seeber A, Hauer M and Gasser SM. 2013. Nucleosome remodelers in double-strand break repair. Curr Opin Genet Dev, 23:174-184.
Shea LD, Woodruff TK, Shikanov A. 2014. Bioengineering the ovarian follicle microenvironment. Annu. Rev. Biomed. Eng. 16:29-52.
Tapias LF, Ott HC. 2014. Decellularized scaffolds as a platform for bioengineered organs. Curr Opin Organ Transplant, 19:145-152.
Telfer EE, McLaughlin M. 2012. Strategies to support human oocyte development in vitro. Int J Dev Biol, 56:901-907.
Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, Dickler M, Robson M, Moy F, Goswami S, Oktay K. 2013. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci Transl Med, 5(172):172ra21.
Vanacker J, Luyckx V, Dolmans MM, Des Rieux A, Jaeger J, Van Langendonckt A, Donnez J, Amorim CA. 2012. Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: first step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells. Biomaterials, 33:6079-6085.
Wallace WH, Anderson RA and Irvine DS. 2005. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol, 6:209-218.
Xu M, Kreeger PK, Shea LD, Woodruff TK. 2006. Tissue-engineered follicles produce live, fertile offspring. Tissue Eng, 9(5):1013-1021.
Yalcinkaya T, Sittadjody S, Opara E. 2014. Scientific principles of regenerative medicine and their application in the female reproductive system. Maturitas, 77(1):12-19.
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