Accelerated and Improved Vascular Maturity after Transplantation of Testicular Tissue in Hydrogels Supplemented with VEGF- and PDGF-Loaded Nanoparticles

Abstract

Avascular transplantation of frozen–thawed testicular tissue fragments represents a potential future technique for fertility restoration in boys with cancer. A significant loss of spermatogonia was observed in xeno-transplants of human tissue most likely due to the hypoxic period before revascularization. To reduce the effect of hypoxia–reoxygenation injuries, several options have already been explored, like encapsulation in alginate hydrogel and supplementation with nanoparticles delivering a necrosis inhibitor (NECINH) or VEGF. While these approaches improved short-term (5 days) vascular surfaces in grafts, neovessels were not maintained up to 21 days; i.e., the time needed for achieving vessel stabilization. To better support tissue grafts, nanoparticles loaded with VEGF, PDGF and NECINH were developed. Testicular tissue fragments from 4–5-week-old mice were encapsulated in calcium-alginate hydrogels, either non-supplemented (control) or supplemented with drug-loaded nanoparticles (VEGF-nanoparticles; VEGF-nanoparticles + PDGF-nanoparticles; NECINH-nanoparticles; VEGF-nanoparticles + NECINH-nanoparticles; and VEGF-nanoparticles + PDGF-nanoparticles + NECINH-nanoparticles) before auto-transplantation. Grafts were recovered after 5 or 21 days for analyses of tissue integrity (hematoxylin–eosin staining), spermatogonial survival (immuno-histo-chemistry for promyelocytic leukemia zinc finger) and vascularization (immuno-histo-chemistry for α-smooth muscle actin and CD-31). Our results showed that a combination of VEGF and PDGF nanoparticles increased vascular maturity and induced a faster maturation of vascular structures in grafts.

Impact of Electronic Cigarette Exposure on the Testes of Adult Male Albino Rat and the Role of Cessation: Histopathological and Biochemical study

“…Moreover, VEGF can inhibit testicular cell apoptosis [52]. Del Vento and his collaborators [53] have recently shown that VEGF increased testicular vascular maturity both structurally and functionally. We reported a significant decrease in testicular VEGF in the Ec group even after E-cigs cessation in W group.…”

Fertility Preservation and Restoration Options for Pre-Pubertal Male Cancer Patients: Current Approaches

“…Bovine testicular tissue treated with vascular endothelial growth factor (VEGF) at the time of implantation in mice ( 121 ) was heavier at recovery than the untreated control and showed a higher percentage of seminiferous tubules containing differentiated cells. Since the early approaches, numerous experiments have begun to treat the tissue with VEGF, whether in the context of autografts in mice ( 122 ), bovine tissue xenografts ( 123 ), and even pre-pubescent human testis xenografts ( 124 ).…”

“…On the pre-pubescent human testis, in vitro pretreatment with VEGF appears to increase vascularization and survival of SSCs and seminiferous tubule integrity ( 124 ). Subsequent experiments ( 122 ) on autograft in mice tested the combined effect of VEGF and platelet-derived growth (PDGF) nanoparticles, showing that the combination of the two factors appears to further improve vascularization. The use of necrosis inhibitor substances also seems promising ( 125 ).…”

The Effects of Prenatal and Postnatal Exposure to 50-Hz and 3 mT Electromagnetic Field on Rat Testicular Development

“…VEGF is synthesized from Sertoli and Leydig cells in the male genital tract, as well as from peritubular cells of the epididymis, prostate epithelial cells, and seminal vesicle. VEGF is very important in germ cell homeostasis and may regulate male fertility in testes [ 29 , 30 , 31 ].…”