Severe inflammatory response and functional impairment of endothelial progenitor cells (EPCs) often lead to the implantation failure of EPC-captured tissue-engineered blood vessels (TEBVs) in diabetes. Regulatory T cells (Treg cells) are the most important inhibitory immune cells, but their effects in angiogenesis remain undefined, and the differences in the microenvironment may be an important reason. Here, we constructed a TEBV coated with an anti-CD34 antibody-functionalized heparin-collagen multilayer (anti-CD34 antibody-modified TEBV) using layer-by-layer self-assembly. Then, TEBVs were implanted into diabetic pigs. All TEBVs remained unobstructed 60 days after implantation, although varying degrees of intimal hyperplasia were detectable. Severe intimal hyperplasia was observed in the control group and peripheral injection of Treg cells group. Intravenous injection of Treg cells significantly inhibited intimal hyperplasia, inflammation, and cell apoptosis. Moreover, intravenous injection increased the proportion of circulating EPCs, while peripheral injection did not have these effects and reduced microvessel density around the TEBV. Interestingly, many Nestin+ cells could be detected in TEBVs, most of which were fusiform, showing the characteristics of smooth-muscle cells. Treg cell intravenous transplantation markedly reduced the number of Nestin+ cells in the TEBV. In conclusion, Treg cells inhibited the intimal hyperplasia of TEBVs in diabetic pigs by promoting EPC mobilization, anti-inflammatory action, and cellular protection.
Malignant pleural effusion is one of the most common complications of advanced lung cancer and there is no effective clinical treatment at present. Here, we constructed an aptamer-siRNA chimeras/PEI/PEG/gold nanoparticle (AuNP)/collagen membrane that can progressively activate T cells by layer by layer assembly. Electron microscope showed this collagen membrane could be divided into 10 layers with a total thickness of 50–80μm, and AuNPs could be observed. Aptamer-siRNA chimeras could bind specifically to OX40+ cells and silencing programmed death receptor-1 (PD-1) gene. In vitro experiments demonstrated that chimeras/PEI/PEG/AuNPs gradually activated T cells to continuously kill lung adenocarcinoma cells in malignant pleural effusion. Animal experiments showed that chimeras/PEI/PEG/AuNP/collagen membrane effectively treated malignant pleural effusion. Compared with PD-1 inhibitor group, the number of cancer cells, ki-67 proliferation index and CD44 expression in the pleural effusion was significantly decreased and the lymphocyte/cancer cell ratio was significantly increased in the chimeras/AuNP-CM group. Flow cytometry showed that compared with PD-1 inhibitor group, T cell number in the chimeras/AuNP-CM group was significantly increased, while the proportion of PD-1+ T cells was markedly decreased. In conclusion, we constructed an chimeras/PEI/PEG/AuNP/collagen membrane, which was more effective in the treatment of malignant pleural effusion, and had less side effects than PD-1 inhibitors.
15 February 2026 in Experimental Hematology & Oncology
The tumor microenvironment (TME) has a profound influence on the progression of lung adenocarcinoma (LUAD) and its response to therapy. We identified a tum