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Novel extra cellular-like matrices to improve human ovarian grafting

  • Fertility Preservation
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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).

Author information

Author notes

  1. Yossi Taieb & Rinat Gabbay-Benziv

    Present address: Department of Dermatology, Rabin Medical Center, Petach Tikvah, Israel

  2. Ronit Abir, Dana Stav and Yossi Taieb contributed equally to this work, and, therefore, should be considered joint first authors.

Authors and Affiliations

  1. IVF and Infertility Unit, Beilinson Women Hospital, Rabin Medical Center, 49100, Petach Tikva, Israel

    Ronit Abir, Dana Stav, Yossi Taieb, Rinat Gabbay-Benziv, Moria Kirshner, Avi Ben-Haroush, Benjamin Fisch & Yoel Shufaro

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Ramat Aviv, Israel

    Ronit Abir, Dana Stav, Yossi Taieb, Rinat Gabbay-Benziv, Avi Ben-Haroush, Enrique Freud, Shifra Ash, Isaac Yaniv, Michal Herman-Edelstein, Benjamin Fisch & Yoel Shufaro

  3. The Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikvah, Israel

    Ronit Abir, Michal Herman-Edelstein, Benjamin Fisch & Yoel Shufaro

  4. Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel

    Rinat Gabbay-Benziv

  5. Department of Pediatric Surgery, Schneider Children’s Medical Center of Israel, Petach Tikvah, Israel

    Enrique Freud

  6. Department of Pediatric Hematology Oncology, Schneider Children’s Medical Center of Israel, Petach Tikvah, Israel

    Shifra Ash & Isaac Yaniv

  7. Department of Nephrology, Rabin Medical Center, Petach Tikvah, Israel

    Michal Herman-Edelstein

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  1. Ronit Abir
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Contributions

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.

Corresponding author

Correspondence to Ronit Abir.

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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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