Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia, 30100, Murcia, Spain; Departamento de Biología Celular e Histología, Facultad de Medicina, Universidad de Murcia, 30120, Murcia, Spain.
Instituto Murciano de Investigación Biosanitaria Pascual Parrilla (IMIB), Campus de Ciencias de la Salud, 30120, Murcia, Spain.
Theriogenology. 2025 Jan 1;231:36-51. doi: 10.1016/j.theriogenology.2024.10.005. Epub 2024 Oct 9.
Decellularized extracellular matrix (dECM) are widely utilized in regenerative medicine and tissue engineering due to their ability to promote cell growth, proliferation, and differentiation. In reproduction, research is focused on the utilization of these scaffolds to treat pathologies causing reproductive dysfunction or to improve assisted reproduction technologies (ARTs). We developed an efficient protocol employing the immersion-agitation technique to decellularize porcine oviductal and uterine sections, comparing the efficacy of fresh versus frozen treatments. Both methods successfully generated acellular matrices with less than 3 % residual DNA, effectively preserving structural and protein integrity. Scanning and transmission electron microscopy confirmed the ultrastructural integrity, whereas Masson's Trichrome staining highlighted better collagen preservation in frozen treatments. Proteomic analysis of decellularized scaffolds revealed collagen and key macromolecules such as laminin, filamin, dermatopontin, and fibronectin, which are essential for extracellular matrix structure and cell functions such as adhesion and migration. Innovatively, we assessed the biocompatibility and cytotoxicity of the scaffolds using spermatozoa, demonstrating that thorough washing ensures the scaffold biocompatibility without compromising sperm viability or motility. Our findings not only contribute to the standardization of decellularization protocols for female reproductive organs but also emphasize the importance of evaluating sperm biocompatibility to ensure the safety of dECM scaffolds.
去细胞细胞外基质 (dECM) 由于能够促进细胞生长、增殖和分化,因此在再生医学和组织工程中得到了广泛应用。在生殖领域,研究集中在利用这些支架来治疗导致生殖功能障碍的疾病或改善辅助生殖技术 (ART)。我们开发了一种使用浸泡-搅拌技术来对猪输卵管和子宫段进行去细胞化的有效方案,比较了新鲜处理和冷冻处理的效果。这两种方法都成功地生成了残留 DNA 少于 3%的无细胞基质,有效地保持了结构和蛋白质的完整性。扫描和透射电子显微镜证实了超微结构的完整性,而 Masson 三色染色突出显示了冷冻处理中胶原的更好保存。去细胞支架的蛋白质组学分析揭示了胶原蛋白和关键的大分子,如层粘连蛋白、细丝蛋白、皮肤桥蛋白和纤维连接蛋白,这些对于细胞外基质的结构和细胞功能如粘附和迁移是必不可少的。创新性地,我们使用精子评估了支架的生物相容性和细胞毒性,证明彻底清洗可以确保支架的生物相容性,而不会影响精子的活力或运动能力。我们的研究结果不仅为女性生殖器官的去细胞化方案标准化做出了贡献,还强调了评估精子生物相容性的重要性,以确保 dECM 支架的安全性。