Novel extra cellular-like matrices to improve human ovarian grafting
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FERTILITY PRESERVATION
Novel extra cellular-like matrices to improve human ovarian grafting Ronit Abir 1,2,3 & Dana Stav 1,2 & Yossi Taieb 1,2,4 & Rinat Gabbay-Benziv 1,2,5 & Moria Kirshner 1 & Avi Ben-Haroush 1,2 & Enrique Freud 2,6 & Shifra Ash 2,7 & Isaac Yaniv 2,7 & Michal Herman-Edelstein 2,3,8 & Benjamin Fisch 1,2,3 & Yoel Shufaro 1,2,3 Received: 4 November 2019 / Accepted: 14 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose To investigate if human ovarian grafting with pure virgin human recombinant collagen type-1 from bioengineered plant lines (CollPlant™) or small intestine submucosa (SIS) yields better implantation results for human ovarian tissue and which method benefits more when combined with the host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A. Methods Human ovarian tissue wrapped in CollPlant or SIS was transplanted into immunodeficient mice with/without host/graft treatment. The tissue was assessed by follicle counts (including atretic), for apoptosis evaluation by terminal deoxynucleotidyl transferase assay and for immunohistochemical evaluation of neovascularization by platelet endothelial cell adhesion molecule (PECAM) expression, and for identification of proliferating granulosa cells by Ki67 expression. Results Human ovarian tissue transplanted with CollPlant or SIS fused with the surrounding tissue and promoted neovascularization. In general, implantation with CollPlant even without additives promoted better results than with SIS: significantly higher number of recovered follicles, significantly fewer atretic follicles, and significantly more granulosa cell proliferation. Moreover, results with CollPlant alone seemed to be at least as good as those after host and graft treatments. Conclusions CollPlant is a biomaterial without any potential risks, and grafting ovarian tissue with CollPlant is easy and the procedure may be easily modified, with limited or no foreseeable risks, for auto-transplantation in cancer survivors. Further studies are needed using other novel methods capable of enhancing neovascularization and reducing apoptosis and follicle atresia. Keywords Ovarian transplantation . Immunodeficient mice . CollPlant . SIS . Neovascularization . Stroma cell apoptosis . Atretic follicles
Ronit Abir, Dana Stav and Yossi Taieb contributed equally to this work, and, therefore, should be considered joint first authors. This work was part of the requirements for a "Medical Doctor" degree at the Sackler Faculty of medicine, Tel-Aviv University, Israel for Dana Stav and Yossi Taieb. * Ronit Abir [email protected]; [email protected] 1
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IVF and Infertility Unit, Beilinson Women Hospital, Rabin Medical Center, 49100 Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Ramat Aviv, Israel The Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikvah, Israel
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Present address: Department of Dermatology, Rabin Medical Center, Peta
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