Endothelial cell supplementation promotes xenograft revascularization during short-term ovarian tissue transplantation

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2025-04-16 DOI:10.1016/j.bioactmat.2025.03.021

Mariagiulia Spazzapan , Silvia Pegoraro , Roman Vuerich , Gabriella Zito , Andrea Balduit , Elena Longo , Lorella Pascolo , Miriam Toffoli , Giorgia Meshini , Alessandro Mangogna , Gloria Ros , Francesca Buonomo , Federico Romano , Letizia Lombardelli , Giovanni Papa , Marie-Pierre Piccinni , Serena Zacchigna , Chiara Agostinis , Roberta Bulla , Giuseppe Ricci

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Abstract

The ischemic/hypoxic window after Ovarian Tissue Transplantation (OTT) can be responsible for the loss of more than 60 % of follicles. The implantation of the tissue supplemented with endothelial cells (ECs) inside dermal substitutes represents a promising strategy for improving graft revascularization. Ovarian biopsies were partly cryopreserved and partly digested to isolate ovarian ECs (OVECs). Four dermal substitutes (Integra®, made of bovine collagen enriched with chondroitin 6-sulfate; PELNAC®, composed of porcine collagen; Myriad Matrix®, derived from decellularized ovine forestomach; and NovoSorb® BMT, a foam of polyurethane) were compared for their angiogenic bioactive properties.

OVECs cultured onto the scaffolds upregulated the expression of angiogenic factors, supporting their use in boosting revascularization. Adhesion and proliferation assays suggested that the most suitable scaffold was the bovine collagen one, which was chosen for further in vivo experiments. Cryopreserved tissue was transplanted onto the 3D scaffold in immunodeficient mice with or without cell supplementation, and after 14 days, it was analyzed by immunofluorescence (IF) and X-ray phase contrast microtomography. The revascularization area of OVECs-supplemented tissue was doubled (7.14 %) compared to the scaffold transplanted alone (3.67 %). Furthermore, tissue viability, evaluated by nuclear counting, was significantly higher (mean of 169.6 nuclei/field) in the tissue grafted with OVECs than in the tissue grafted alone (mean of 87.2 nuclei/field).

Overall, our findings suggest that the OVECs-supplementation shortens the ischemic interval and may significantly improve fertility preservation procedures.

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补充内皮细胞促进短期卵巢组织移植异种移植物血运重建

卵巢组织移植（OTT）后的缺血/缺氧窗口可能导致超过60%的卵泡丢失。在真皮替代物内植入内皮细胞（ECs）补充组织是改善移植物血运重建的一种有希望的策略。卵巢活检部分冷冻保存，部分消化分离卵巢ECs （OVECs）。四种真皮替代品(Integra®，由富含6-硫酸软骨素的牛胶原制成；PELNAC®，由猪胶原蛋白组成；Myriad Matrix®，来源于去细胞化的羊前胃；与NovoSorb®BMT（一种聚氨酯泡沫）进行了血管生成生物活性性能的比较。在支架上培养的ovec上调血管生成因子的表达，支持其在促进血运重建中的作用。黏附和增殖实验表明，牛胶原蛋白是最合适的支架材料，并将其用于进一步的体内实验。将冷冻保存的组织移植到免疫缺陷小鼠的3D支架上，并补充或不补充细胞，14天后，通过免疫荧光（IF）和x射线相衬显微断层扫描分析。与单纯支架移植（3.67%）相比，补充ovec的组织血运重建面积增加了一倍（7.14%）。此外，通过核计数评估的组织活力（平均169.6个核/场）明显高于单独移植的组织（平均87.2个核/场）。总的来说，我们的研究结果表明，补充ovec可缩短缺血间隔，并可能显著改善生育保存程序。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.