Bandstein Sara, De Miguel-Gómez Lucia, Sehic Edina, Thorén Emy, López-Martínez Sara, Cervelló Irene, Akouri Randa, Oltean Mihai, Brännström Mats, Hellström Mats
Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Department of Obstetrics and Gynecology, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
Bioengineering (Basel). 2024 Dec 14;11(12):1268. doi: 10.3390/bioengineering11121268.
Transplantation of decellularized uterus tissue showed promise in supporting regeneration following uterine injury in animal models, suggesting an alternative to complete uterus transplantation for uterine factor infertility treatment. However, most animal studies utilized small grafts, limiting their clinical relevance. Hence, we used larger grafts (20 × 10 mm), equivalent to nearly one uterine horn in rats, to better evaluate the bioengineering challenges associated with structural support, revascularization, and tissue regeneration. We analyzed histopathology, employed immunohistochemistry, and investigated gene expression discrepancies in growth-related proteins over four months post-transplantation in acellular grafts and those recellularized (RC) with bone marrow-derived mesenchymal stem cells (bmMSCs). RC grafts exhibited less inflammation and faster epithelialization and migration of endogenous cells into the graft compared with acellular grafts. Despite the lack of a significant difference in the density of CD31 positive blood vessels between groups, the RC group demonstrated a better organized myometrial layer and an overall faster regenerative progress. Elevated gene expression for , , and correlated with the enhanced tissue regeneration in this group. Elevated expression was noted in both groups, potentially contributing to the rapid revascularization. Our findings suggest that large uterine injuries can be regenerated using decellularized tissue, with bmMSCs enhancing the endogenous repair mechanisms.
脱细胞子宫组织移植在支持动物模型子宫损伤后的再生方面显示出前景，这为子宫因素不孕症的治疗提供了一种替代全子宫移植的方法。然而，大多数动物研究使用的是小移植物，限制了它们的临床相关性。因此，我们使用了更大的移植物（20×10毫米），相当于大鼠近一个子宫角的大小，以更好地评估与结构支持、血管再生和组织再生相关的生物工程挑战。我们分析了组织病理学，采用了免疫组织化学，并研究了脱细胞移植物和用骨髓间充质干细胞（bmMSCs）重新细胞化（RC）的移植物在移植后四个月内生长相关蛋白的基因表达差异。与脱细胞移植物相比，RC移植物表现出更少的炎症，内源性细胞向移植物的上皮化和迁移更快。尽管两组之间CD31阳性血管密度没有显著差异，但RC组的肌层组织更有序，整体再生进程更快。该组中、和的基因表达升高与组织再生增强相关。两组中均观察到表达升高，这可能有助于快速血管再生。我们的研究结果表明，使用脱细胞组织可以再生大型子宫损伤，bmMSCs可增强内源性修复机制。
