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.
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Acknowledgments
We are grateful to Ms. Gloria Ganzach from the Editorial Board of Rabin Medical Center for the English editing and to Ms. Carmela Felz for the histological sections.
Funding
The study was partially funded by a research grant from the Israel Ministry of Health (for R.A. and B.F. no 3-6098-00000).
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R. Abir designed the study and collected the data, assisted in IMH studies and viewed the sections, conducted most of the statistical analysis, and wrote most of the manuscript. D. Stav conducted the CollPlant part of the study, wrote parts of the manuscript, and edited all the figures. Y. Taib conducted the SIS part of the study and wrote parts of the manuscript. R. Gabbay-Benziv conducted the SIS transplantations, assisted in the various drafts of the manuscript and in the analysis of the results, and approved its final version and also suggested the use of CollPlant. M. Kirshner conducted the CollPlant transplantations, assisted in the various drafts of the manuscript and in the analysis of the results, and approved its final version. A. Ben-Haroush provided some of the ovarian samples and reviewed the final draft of the manuscript. E. Freud performed the surgery on the patients, wrote certain parts of the manuscript, and critically proofed the final manuscript. S. Ash recruited most of the patients, helped in writing the manuscript, and critically proofed the final manuscript. I. Yaniv recruited most of the patients, helped in writing the manuscript, and critically proofed the final manuscript. M. Herman-Edelstein contributed the positive PECAM control, helped in writing the manuscript, and critically proofed the revised manuscript. B. Fisch assisted in designing the study, assisted in the various drafts of the manuscript, the analysis of the results, and approved its final version. Y. Shufaro assisted in designing the study, assisted in the various drafts of the manuscript, the analysis of the results, and approved its final version.
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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.
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Abir, R., Stav, D., Taieb, Y. et al. Novel extra cellular-like matrices to improve human ovarian grafting. J Assist Reprod Genet 37, 2105–2117 (2020). https://doi.org/10.1007/s10815-020-01832-4
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DOI: https://doi.org/10.1007/s10815-020-01832-4