Bogomolova Alexandra, Ermakova Polina, Potapov Arseniy, Mozherov Artem, Tselousova Julia, Vasilchikova Ekaterina, Kashina Alexandra, Zagaynova Elena
Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow 119334, Russia.
Federal State Budgetary Institution of Higher Education, "Privolzhsky Research Medical University" of the Ministry of Health of Russia, Nizhny Novgorod 603082, Russia.
Int J Mol Sci. 2025 Jul 12;26(14):6692. doi: 10.3390/ijms26146692.
The treatment of type 1 diabetes through pancreatic islet transplantation faces significant limitations, including donor organ shortages and poor islet survival due to post-transplantation loss of extracellular matrix support and inadequate vascularization. Developing biocompatible scaffolds that mimic the native islet microenvironment could substantially improve transplantation outcomes. This study aimed to create and evaluate decellularized (DCL) matrices from porcine organs as potential platforms for islet transplantation. Porcine lung and pancreatic tissues were decellularized using four different protocols combining detergents (Triton X-100, SDS and SDC) with optimized incubation times. The resulting matrices were characterized through DNA quantification and histological staining (H&E and Van Gieson). Islet viability was assessed in vitro using Live/Dead staining after 3 and 7 days of culture on the matrices. In vivo biocompatibility was evaluated by implanting matrices into rat omentum or peritoneum, with histological analysis at 1-, 4-, and 8 weeks post-transplantation. Protocols 3 (for lung tissue) and 4 (for pancreas tissue) demonstrated optimal decellularization efficiency with residual DNA levels below 8%, while preserving the collagen and elastin networks. In vitro, islets cultured on decellularized lung matrix had maintained 95% viability by day 7, significantly higher than the controls (60%) and pancreatic matrix (83%). The omentum showed superior performance as an implantation site, exhibiting minimal inflammation and fibrosis compared to the peritoneum sites throughout the 8-week study period. These findings establish DCL as a promising scaffold for islet transplantation due to its superior preservation of ECM components and excellent support of islet viability. This work provides a significant step toward developing effective tissue-engineered therapies for diabetes treatment.
通过胰岛移植治疗1型糖尿病面临重大限制，包括供体器官短缺以及由于移植后细胞外基质支持丧失和血管化不足导致的胰岛存活率低。开发能够模拟天然胰岛微环境的生物相容性支架可显著改善移植结果。本研究旨在制备并评估来自猪器官的脱细胞（DCL）基质作为胰岛移植的潜在平台。使用四种不同方案将去污剂（Triton X-100、SDS和SDC）与优化的孵育时间相结合，对猪肺和胰腺组织进行脱细胞处理。通过DNA定量和组织学染色（苏木精和伊红染色以及范吉森染色）对所得基质进行表征。在基质上培养3天和7天后，使用活/死染色法在体外评估胰岛活力。通过将基质植入大鼠大网膜或腹膜来评估体内生物相容性，并在移植后1周、4周和8周进行组织学分析。方案3（用于肺组织）和方案4（用于胰腺组织）显示出最佳的脱细胞效率，残留DNA水平低于8%，同时保留了胶原蛋白和弹性蛋白网络。在体外，在脱细胞肺基质上培养的胰岛到第7天保持了95%的活力，显著高于对照组（60%）和胰腺基质（83%）。在整个8周的研究期间，大网膜作为植入部位表现出更好的性能，与腹膜部位相比，炎症和纤维化程度最小。这些发现表明，由于其对细胞外基质成分的卓越保留和对胰岛活力的出色支持，DCL是一种有前景的胰岛移植支架。这项工作朝着开发有效的糖尿病组织工程治疗方法迈出了重要一步。
