Ronit Abir1,2,3, Dana Stav4,5, Yossi Taieb4,5,6, Rinat Gabbay-Benziv4,5,7, Moria Kirshner4, Avi Ben-Haroush4,5, Enrique Freud5,8, Shifra Ash5,9, Isaac Yaniv5,9, Michal Herman-Edelstein5,10,11, Benjamin Fisch4,5,10, Yoel Shufaro4,5,10. 1. IVF and Infertility Unit, Beilinson Women Hospital, Rabin Medical Center, 49100, Petach Tikva, Israel. ronita@clalit.org.il. 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Ramat Aviv, Israel. ronita@clalit.org.il. 3. The Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikvah, Israel. ronita@clalit.org.il. 4. IVF and Infertility Unit, Beilinson Women Hospital, Rabin Medical Center, 49100, Petach Tikva, Israel. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Ramat Aviv, Israel. 6. Department of Dermatology, Rabin Medical Center, Petach Tikvah, Israel. 7. Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel. 8. Department of Pediatric Surgery, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel. 9. Department of Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel. 10. The Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikvah, Israel. 11. Department of Nephrology, Rabin Medical Center, Petach Tikvah, Israel.
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.
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 immunodeficientmice 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.
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Authors: Luca Salvatore; Nunzia Gallo; Maria Lucia Natali; Alberta Terzi; Alessandro Sannino; Marta Madaghiele Journal: Front Bioeng Biotechnol Date: 2021-04-27
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