Novel extra cellular-like matrices to improve human ovarian grafting

J Assist Reprod Genet. 2020 Sep;37(9):2105-2117. doi: 10.1007/s10815-020-01832-4. Epub 2020 Jul 24.


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: Atretic follicles; CollPlant; Immunodeficient mice; Neovascularization; Ovarian transplantation; SIS; Stroma cell apoptosis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cancer Survivors
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Humans
  • Ki-67 Antigen / genetics
  • Melatonin / pharmacology
  • Mice
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / growth & development
  • Ovarian Follicle / transplantation*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / rehabilitation
  • Ovarian Neoplasms / therapy*
  • Ovary / drug effects
  • Ovary / growth & development
  • Ovary / transplantation*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Transplantation, Homologous / methods*


  • Ki-67 Antigen
  • Pecam1 protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Melatonin