Accelerated and Improved Vascular Maturity after Transplantation of Testicular Tissue in Hydrogels Supplemented with VEGF- and PDGF-Loaded Nanoparticles.
Federico Del VentoJonathan PoelsMaxime VermeulenBernard UcakarMaria Grazia GiudiceMarc KanbarAnne des RieuxChristine WynsPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- acute coronary syndrome
- endothelial cells
- smooth muscle
- drug delivery
- vascular endothelial growth factor
- walled carbon nanotubes
- emergency department
- young adults
- randomized controlled trial
- oxidative stress
- metabolic syndrome
- mesenchymal stem cells
- staphylococcus aureus
- vascular smooth muscle cells
- current status
- skeletal muscle
- insulin resistance
- mass spectrometry
- stem cells
- signaling pathway
- coronary artery disease
- pseudomonas aeruginosa
- risk assessment
- cell migration
- candida albicans
- flow cytometry
- wild type
- tissue engineering
- electronic health record