RT Journal Article
SR Electronic
T1 Effects of bacterial lipopolysaccharide and Shiga Toxin on induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.07.459335
DO 10.1101/2021.09.07.459335
A1 Daiana Martire-Greco
A1 Alejandro La Greca
A1 Luis Castillo Montañez
A1 Celeste Biani
A1 Antonella Lombardi
A1 Federico Birnberg-Weiss
A1 Alessandra Norris
A1 Flavia Sacerdoti
A1 María Marta Amaral
A1 Nahuel Rodrigues-Rodriguez
A1 Jose Ramón Pittaluga
A1 Verónica Alejandra Furmento
A1 Verónica Inés Landoni
A1 Santiago Gabriel Miriuka
A1 Carlos Luzzani
A1 Gabriela Cristina Fernández
YR 2021
UL http://biorxiv.org/content/early/2021/09/23/2021.09.07.459335.abstract
AB Background Mesenchymal Stem Cells can be activated and respond to different bacterial toxins. Lipopolysaccharides (LPS) and Shiga Toxin (Stx) are the two main bacterial toxins present in Hemolytic Uremic Syndrome (HUS) that cause endothelial damage. In this work we aimed to study the response of iPSC-MSC to LPS and/or Stx and its effect on the restoration of injured endothelial cells.Methods iPSC-MSC were used as a source of mesenchymal stem cells (MSC) and Human Microvascular Endothelial Cells-1 (HMEC-1) as a source of endothelial cells. iPSC-MSC were treated or not with LPS and/or Stx. For some experiments, Conditioned Media (CM) were collected from each plate and incubated with an anti-Stx antibody to block the direct effect of Stx, or Polymyxin to block the direct effect of LPS. In CM from both treatments, anti-Stx and Polymyxin were used. Results are expressed as mean ± S.E.M. Significant differences (p<0.05) were identified using one way analysis of variance (ANOVA) and Bonferroni’s Multiple comparison test.Results The results obtained showed that LPS induced a pro-inflammatory profile on iPSC-MSC, but not Stx, even though they expressed Gb3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to gelatin substrate. Also, the addition of CM of iPSC-MSC treated with LPS+Stx, decreased the capacity of HMEC-1 to close a wound, and did not favor the formation of new tubes. Proteomic analysis of iPSC-MSC treated with LPS and/or Stx revealed specific protein secretion patterns that support many of the functional results described here.Conclusions In conclusion, these results suggest that iPSC-MSC activated by LPS acquired a pro-inflammatory profile that induces migration and adhesion to extracellular matrix proteins (ECM), but the combination LPS+Stx decreased the repair of endothelial damage. The importance of this work is that it provides knowledge to understand the context in which iPSC-MSC could benefit or not the restoration of tissue injury, taking into account that the inflammatory context in response to a particular bacterial toxin is relevant for iPSC-MSC immunomodulation.Competing Interest StatementThe authors have declared no competing interest.