title: Transplantation of testicular tissue in alginate hydrogel loaded with VEGF nanoparticles improves spermatogonial recovery.
abstract: Transplantation of cryopreserved immature testicular tissue (ITT) is a promising strategy to restore fertility in young boys facing gonadotoxic treatments. However, up to now, limited spermatogonial recovery has been achieved in xenografting models used to evaluate the potential of cryopreserved tissue transplantation. When comparing avascular xenografts of cryopreserved and fresh human ITT into a mouse model, the number of spermatogonia was significantly reduced, regardless of the cryopreservation procedure used. To improve tissue engraftment, revascularization and hence spermatogonial survival, ITT was embedded in two types of hydrogel loaded with VEGF nanoparticles. Small pieces (±1mm(3)) of testicular tissue were grafted in NMRI mice as follows: grafted without encapsulation, grafted after encapsulation in fibrin, in alginate, in fibrin-VEGF-nanoparticle (NP) and in alginate-VEGF-NP. Non-grafted tissue served as control. After 5 and 21days of implantation, seminiferous tubule integrity, revascularization and spermatogonial recovery were evaluated by histology and immunohistochemistry. Seminiferous tubule integrity ranged from 13.3% to 39.6% and 42.7% to 68.7% on day 5 and day 21, respectively. Vascular density on day 5 was found to be higher in VEGF supplemented groups, regardless of the hydrogel used. Staining for phosphorylated VEGF receptor 2 and endothelial proliferation on day 5 was higher in all groups compared to non-grafted avascular controls. Spermatogonial recovery ranged between 14.8% and 27.3% on day 21 and was significantly higher in the alginate and alginate-VEGF-NP groups. The present study demonstrates the potential of alginate hydrogel loaded with nanoencapsulated growth factors to improve cryopreserved tissue engraftment.
authors.affiliation: Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Poels
authors.affiliation: Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
authors.forename: Gaël
authors.initials: G
authors.lastname: Abou-Ghannam
authors.affiliation: Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Decamps
authors.affiliation: Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Leyman
authors.affiliation: Advanced Drug Delivery and Biomaterials Unit, Louvain Drug Research Institute, Université Catholique de Louvain, 1200 Brussels, Belgium; Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.
authors.forename: Anne des
authors.initials: Ad
authors.lastname: Rieux
authors.affiliation: Gynecology-Andrology Unit, Medical School, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Gynecology-Andrology, Cliniques Universitaires Saint-Luc, 1200, Brussels, Belgium. Electronic address: christine.wyns@uclouvain.be.
authors.forename: Christine
authors.initials: C
authors.lastname: Wyns
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015925:Cryopreservation; D065546:Drug Liberation; D059247:Fertility Preservation / Q000379:methods*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000008:administration & dosage*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012671:Seminiferous Tubules / Q000187:drug effects; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects*; D013737:Testis / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; D020723:Glucuronic Acid
keywords: Angiogenesis; Fertility preservation; Hydrogel; Nanoparticles; Testicular tissue transplantation; VEGF