Perez-Basterrechea Marcos, Esteban Manuel Martinez, Alvarez-Viejo Maria, Fontanil Tania, Cal Santiago, Sanchez Pitiot Marta, Otero Jesus, Obaya Alvaro Jesus
Unidad de Trasplantes, Terapia Celular y Medicina Regenerativa, Hospital Universitario Central de Asturias, Oviedo, Spain.
Departamento de Biologia Funcional, Universidad de Oviedo, Oviedo, Spain.
PLoS One. 2017 Jul 3;12(7):e0180695. doi: 10.1371/journal.pone.0180695. eCollection 2017.
Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.
多年来，胰岛移植一直被认为是1型糖尿病患者β细胞替代的一种有前景的治疗方法，尽管长期临床结果并不尽如人意。这一事实表明，有必要设计策略来改善和加速胰岛植入，尤其要关注确保其血管再生的相关事件。成纤维细胞是一类参与组织稳态维持的细胞群体，它能保持结构成分合成与降解之间的平衡，并维持所需的存活因子数量。我们的研究小组开发了一种皮下胰岛移植模型，使用一种基于血浆的支架，其中包含成纤维细胞作为辅助细胞，该模型能够使糖尿病小鼠实现血糖控制。移植组织的植入在移植后的头几天至关重要，因此我们深入研究了成纤维细胞在胰岛移植后头十天内对移植组织的支持作用。所有移植了包埋在基于血浆支架中的胰岛的小鼠均逆转了高血糖，尽管只有移植含成纤维细胞支架的组维持了长期血糖控制。通过在最初几天进行基因表达分析和组织学检查，我们可以得出结论，这些差异可能是由于移植中有成纤维细胞时检测到血管发育以及β细胞再生相关基因的过表达所致。此外，成纤维细胞的存在与更快的移植组织血管再生、更高的胰岛素阳性面积以及更低的细胞死亡相关。因此，这项工作强调了成纤维细胞作为胰岛移植辅助细胞的重要性，并表明其可能用于其他移植支持策略中。
