Isoform 165 of vascular endothelial growth factor in collagen matrix improves ovine cryopreserved ovarian tissue revascularisation after xenotransplantation in mice

Abstract

BackgroundAggressive anti-cancer treatments can result in ovarian failure. Ovarian cryopreservation has been developed to preserve the fertility of young women, but early graft revascularisation still requires improvement.MethodsFrozen/thawed sheep ovarian cortical biopsies were embedded in collagen matrix with or without isoform 165 of vascular endothelial growth factor (VEGF165) and transplanted into ovaries of immunodeficient mice. Ovaries were chosen as transplantation sites to more closely resemble clinical conditions in which orthotopic transplantation has previously allowed several spontaneous pregnancies.ResultsWe found that VEGF165 significantly increased the number of Dextran-FITC positive functional vessels 3 days after grafting. Dextran- fluorescein isothiocyanate (FITC) positive vessels were detectable in 53% and 29% of the mice in the VEGF-treated and control groups, respectively. Among these positive fragments, 50% in the treated group displayed mature smooth-muscle-actin-alpha (alpha-SMA) positive functional vessels compared with 0% in the control group. CD31 positive murine blood vessels were observed in 40% of the VEGF165 transplants compared with 21% of the controls. After 3 weeks, the density of murine vessels was significantly higher in the VEGF165 group.ConclusionThe encapsulation of ovarian tissue in collagen matrix in the presence of VEGF165 before grafting has a positive effect on functional blood vessel recruitment. It can be considered as a useful technique to be improved and further developed before human clinical applications in female cancer patients in the context of fertility preservation.

Effect of recombinant human vascular endothelial growth factor on testis tissue xenotransplants from prepubertal boys: a three-case study

“…Administration of VEGF, either by culture of the tissue before transplantation or by hydrogel delivery, promoted angiogenesis, follicular survival and enhanced the function of ovarian tissue xenotransplants, including human (Shikanov et al, 2011;Labied et al, 2013;Wang et al, 2013;Henry et al, 2015;Langbeen et al, 2016;Tavana et al, 2016). A previous study on autotransplantation of mouse ITT revealed a positive short-term effect of VEGF on transplant neovascularization 5 and 21 days post-transplantation (Poels et al, 2016), whereas the enhancement of germ cell survival has been demonstrated in several species, including mouse, pig and bovine (Schmidt et al, 2006;Caires et al, 2009Caires et al, , 2012Dores and Dobrinsky, 2014;Poels et al, 2016, Tian et al, 2016.…”

Scaffold-based delivery of adipose tissue-derived stem cells in rat frozen-thawed ovarian autografts: preliminary studies in a rat model

“…In animal models, it has been increasingly common to transplant ovarian tissue installed in acellular scaffolds of materials such as fibrin [11][12][13], alginate [14], Matrigel [15], and collagen [16]. However, there is still no consensus on the ideal material.…”

In vitro evaluation of the anti-apoptotic drug Z-VAD-FMK on human ovarian granulosa cell lines for further use in ovarian tissue transplantation

“…Moreover, in a previous study, granulosa cells, more so than oocytes, were identified as the main cells affected by the freeze/thaw processing of ovarian tissue [13]. Granulosa cells seem to be able to respond to hypoxia by increasing their synthesis of vascular endothelial growth factor (VEGF) [14], which is an important angiogenic factor that could reduce the hypoxic period post-transplantation, as previously shown in ovarian grafting studies [11,[15][16][17][18][19][20]. Because of the restricted availability and relatively short life span of primary cultures of granulosa cells, human granulosa cell lines were developed to facilitate research [21].…”