Biology subjects

Bordin, A.

Publications and source records attributed to Bordin, A..

3 recordsLinked to original sources

bioRxiv2022

Investigating the risk of cardiac fibrosis due to heat-not-burn cigarettes through human cardiac stromal cells

BackgroundThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. ObjectiveTo investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs). MethodsResident CSCs were isolated from the atrial tissue of patients with cardiovascular diseases, and exposed to the serum of 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference. ResultsCSCs treated with TCC serum displayed impaired 3D growth and migration, as well as increased expression and/or release of pro-inflammatory and pro-fibrotic cytokines. Cells cultured with HNBC serum showed increased mRNA levels of pro-fibrotic genes, and reduced expression of the gap junction protein CX43. Nonetheless, both TCC and HNBC sera reduced the release of angiogenic and protective factors from CSCs. In fact, their paracrine support to tube-formation by endothelial cells and to preserved cell viability of cardiomyocytes in culture was significantly impaired. Treatment with the sera of both types of smokers also increased the expression of NOX isoforms and the release of H2O2 by CSCs. ConclusionThe circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use. CONDENSED ABSTRACTThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. We isolated human stromal cells from the atrial tissue of patients with cardiovascular diseases, and exposed them to the serum of young healthy subjects, that are exclusive HNBC smokers. Results showed significant alterations in the phenotype of CSCs exposed to HNBC serum, suggesting a specification towards fibrosis, reduced support to parenchymal cells, and increased oxidative stress production. Data point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.

pathology↗

bioRxiv2022

Remote adipose tissue-derived stromal cells of patients with lung adenocarcinoma generate a similar malignant microenvironment of the lung stromal counterpart

Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumor may alter distant niches of stromal cells is still unclear, expecially at early stages. In this short report we attempt to better understand the biology of this cross talk. In our "autologous stromal experimental setting", we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similarly to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analysed by arrays, a small pool of 5 upregulated molecules including IL1-{beta}, IL-3, MCP-1, TNF- and EGF, was commonly shared by both malignant-like autologous A- and LMSC derived microenvironments vs those benign. The bioinformatic analysis both revealed that these proteins were strictly and functionally interconnected to the lung fibrosis and proinflammation and that miR-126, 101, 486 and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively.

cell biology↗

bioRxiv2022

Human platelet lysate derived extracellular vesicles enhance angiogenesis through miR-126

Objectivesextracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL. Methodswe tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs. Resultsa subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in HUVEC and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched of small RNAs and a high amount of miR-126, the most abundant angiogenic miRNA in platelets. The transfer of miR-126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as downstream target in this system. ConclusionsPL is a biological source of available EVs with angiogenic effects involving a miRNAs-based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.

cell biology↗