Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, Kvinnokliniken, Blå stråket 6, SE-405 30, Sweden.
Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30, Sweden.
Biomater Sci. 2024 Apr 16;12(8):2136-2148. doi: 10.1039/d3bm01912h.
Innovative bioengineering strategies utilizing extracellular matrix (ECM) based scaffolds derived from decellularized tissue offer new prospects for restoring damaged uterine tissue. Despite successful fertility restoration in small animal models, the translation to larger and more clinically relevant models have not yet been assessed. Thus, our study investigated the feasibility to use a 6 cm graft constructed from decellularized sheep uterine tissue, mimicking a future application to repair a uterine defect in women. Some grafts were also recellularized with fetal sheep bone marrow-derived mesenchymal stem cells (SF-MSCs). The animals were followed for six weeks post-surgery during which blood samples were collected to assess the systemic immune cell activation by fluorescence-activated cell sorting (FACS) analysis. Tissue regeneration was assessed by histology, immunohistochemistry, and gene expression analyses. There was a large intra-group variance which prompted us to implement a novel scoring system to comprehensively evaluate the regenerative outcomes. Based on the regenerative score each graft received, we focused our analysis to map potential differences that may have played a role in the success or failure of tissue repair following the transplantation therapy. Notably, three out of 15 grafts exhibited major regeneration that resembled native uterine tissue, and an additional three grafts showed substantial regenerative outcomes. For the better regenerated grafts, it was observed that the systemic T-cell subgroups were significantly different compared with the failing grafts. Hence, our data suggest that the T-cell response play an important role for determining the uterus tissue regeneration outcomes. The remarkable regeneration seen in the best-performing grafts after just six weeks following transplantation provides compelling evidence that decellularized tissue for uterine bioengineering holds great promise for clinically relevant applications.
利用脱细胞组织衍生的细胞外基质 (ECM) 基支架的创新生物工程策略为恢复受损的子宫组织提供了新的前景。尽管在小动物模型中成功恢复了生育能力，但尚未评估其在更大和更具临床相关性的模型中的转化。因此，我们的研究调查了使用从脱细胞绵羊子宫组织构建的 6 厘米移植物的可行性，该移植物模拟了未来在女性中修复子宫缺陷的应用。一些移植物还与胎羊骨髓来源的间充质干细胞 (SF-MSCs) 再细胞化。在手术后的六周内对动物进行了随访，在此期间收集血液样本通过荧光激活细胞分选 (FACS) 分析评估系统免疫细胞激活情况。通过组织学、免疫组织化学和基因表达分析评估组织再生。由于组内个体差异较大，我们实施了一种新的评分系统来全面评估再生结果。基于每个移植物收到的再生评分，我们集中分析以映射可能在移植治疗后组织修复的成功或失败中起作用的潜在差异。值得注意的是，15 个移植物中有 3 个表现出类似于天然子宫组织的主要再生，另外 3 个移植物表现出明显的再生结果。对于更好的再生移植物，与失败的移植物相比，观察到系统 T 细胞亚群有显著差异。因此，我们的数据表明 T 细胞反应在决定子宫组织再生结果方面起着重要作用。在移植后仅六周就观察到最佳表现的移植物的显著再生，为用于子宫生物工程的脱细胞组织提供了有说服力的证据，表明其具有很大的临床相关应用潜力。
