Use of Simvastatin, Fibrin Clots, and Their Combination to Improve Human Ovarian Tissue Grafting for Fertility Restoration After Anti-Cancer Therapy

Frontiers in Oncology

Eli Anuka¹  Shulamit Levenberg²  Roei Magen³  Elena Tararashkina⁴  Avi Ben-Haroush⁵  Yair Daykan⁵  Galia Oron⁵  Yoel Shufaro⁶  Benjamin Fisch⁶  Ronit Abir⁶ 

[1]Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

[2]Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel

[3]Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

[4]Infertility and IVF Unit, Beilinson Women Hospital, Rabin Medical Center, Petach Tikvah, Israel

[5]Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

[6]The Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

关键词: transplantation;    human ovarian tissue;    immunodeficient mice;    simvastatin;    fibrin clots;    mouse platelet endothelial cell adhesion molecule;   

DOI  :  10.3389/fonc.2020.598026

来源: DOAJ

【 摘 要 】

Anticancer treatments, particularly chemotherapy, induce ovarian damage and loss of ovarian follicles. There are limited options for fertility restoration, one of which is pre-chemotherapy cryopreservation of ovarian tissue. Transplantation of frozen-thawed human ovarian tissue from cancer survivors has resulted in live-births. There is extensive follicular loss immediately after grafting, probably due to too slow graft revascularization. To avoid this problem, it is important to develop methods to improve ovarian tissue neovascularization. The study’s purpose was to investigate if treatment of murine hosts with simvastatin or/and embedding human ovarian tissue within fibrin clots can improve human ovarian tissue grafting (simvastatin and fibrin clots promote vascularization). There was a significantly higher number of follicles in group A (ungrafted control) than in group B (untreated tissue). Group C (simvastatin-treated hosts) had the highest levels of follicle atresia. Group C had significantly more proliferating follicles (Ki67-stained) than groups B and E (simvastatin-treated hosts and tissue embedded within fibrin clots), group D (tissue embedded within fibrin clots) had significantly more proliferating follicles (Ki67-stained) than group B. On immunofluorescence study, only groups D and E showed vascular structures that expressed both human and murine markers (mouse-specific platelet endothelial cell adhesion molecule, PECAM, and human-specific von Willebrand factor, vWF). Peripheral human vWF expression was significantly higher in group E than group B. Diffuse human vWF expression was significantly higher in groups A and E than groups B and C. When grafts were not embedded in fibrin, there was a significant loss of human vWF expression compared to groups A and E. This protocol may be tested to improve ovarian implantation in cancer survivors.

【 授权许可】

Unknown