Novel extra cellular-like matrices to improve human ovarian grafting.

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.

Extracellular-like matrices and leukaemia inhibitory factor for in vitro culture of human primordial follicles.

The possibility of maturing human primordial follicles in vitro would assist fertility restoration without the danger of reseeding malignancies. Leukaemia inhibitory factor (LIF) and certain culture matrices may promote human follicular growth. The present study compared human primordial follicular growth on novel culture matrices, namely human recombinant vitronectin (hrVit), small intestine submucosa (SIS), alginate scaffolds and human recombinant virgin collagen bioengineered in tobacco plant lines (CollPlant). The frozen-thawed ovarian samples that were used had been obtained from girls or young women undergoing fertility preservation. In the first part of the study, 20 samples were cultured for 6 days on hrVit or SIS with basic culture medium alone or supplemented with one of two concentrations of LIF (10ngmL-1 and 100ngmL-1), with and without LIF-neutralising antibody. In the second part of the study, 15 samples were cultured for 6 days on alginate scaffolds or CollPlant matrices with basic culture medium. Follicular development was assessed by follicular counts and classification, Ki67 immunohistochemistry and 17ß-oestradiol and anti-Müllerian hormone measurements in spent media samples. Primordial follicular growth was not enhanced by LIF. Despite some significant differences among the four matrices, none appeared to have a clear advantage, apart from significantly more Ki67-stained follicles on alginate and CollPlant matrices. Further studies of other culture matrices and medium supplements are needed to obtain an optimal system.

Thyroid nodule characterization using Spectral Detector Computed Tomography (SDCT) in comparison to ultrasound.

OBJECTIVE: To characterize thyroid nodules seen on Spectral Detector computed tomography (SDCT) in respect to their Thyroid Imaging Reporting and Data System (TI-RADS) category on Ultrasound (US). METHODS: We included patients that underwent US examination for the evaluation of thyroid nodules and contrast-enhanced SDCT examination of the neck/thorax, between the years 2018-2020. The SDCT and US were performed within 6 months of each other. Only patients with a visible thyroid nodule on SDCT were included. Attenuation measurements of the nodules in Hounsfield units (HU) were performed on the conventional CT images, virtual non-contrast (VNC) images and virtual monoenergetic images of 40 keV and 100 keV. The Iodine concentration, spectral slope and enhancement estimation results of the nodules were measured. We compared the spectral results between two groups of nodules, according to the US report: TI-RADS 2-3 and TI-RADS 4-5 groups. RESULTS: Thirty-eight nodules were included in the study, 22 nodules in the TI-RADS 2-3 group and 16 in the TI-RADS 4-5 group. The nodules of the TI-RADS 4-5 group had significantly higher Iodine concentration measurement, 4.6 ± 1.8 mg/ml, compared to 2.3 ± 1.2 mg/ml in the TI-RADS 2-3 group; significantly higher estimated enhancement, 3.9 ± 1.5, compared to 2.2 ± 0.7; and significantly higher calculated spectral slope, 5.6 ± 2.2 compared to 2.9 ± 1.5 (p < 0.001). CONCLUSION: Spectral results of SDCT may assist in differentiating intermediate-high risk (TI-RADS 4-5) from low risk (TI-RADS 2-3) thyroid nodules. ADVANCES IN KNOWLEDGE: SDCT offers additional information for the characterization of thyroid nodules.