Effects of bacterial lipopolysaccharide and Shiga Toxin on induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells

MARTIRE-GRECO, DAIANA; LA GRECA, ALEJANDRO; MONTAÑEZ, LUIS CASTILLO; BIANI, CELESTE; LOMBARDI, ANTONELLA; BIRNBERG-WEISS, FEDERICO; NORRIS, ALESSANDRA; SACERDOTI, FLAVIA; AMARAL, MARÍA MARTA; RODRIGUES-RODRIGUEZ, NAHUEL; PITTALUGA, JOSE RAMÓN; FURMENTO, VERÓNICA ALEJANDRA; LANDONI, VERÓNICA INÉS; MIRIUKA, SANTIAGO GABRIEL; LUZZANI, CARLOS; FERNÁNDEZ, GABRIELA CRISTINA

SHOCK

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2023

1073-2322

Background Mesenchymal Stem Cells (MSC) can be activated by different bacterial toxins. Lipopolysaccharides (LPS) and Shiga Toxin (Stx) are the main toxins necessary for Hemolytic Uremic Syndrome (HUS) development. The main etiological event in this disease is endothelial damage that causes glomerular destruction. Considering the repairing properties of MSC we aimed to study the response of MSC derived from induced Pluripotent Stem Cells (iPSC-MSC) to LPS and/or Stx and its effect on the restoration of injured endothelial cells.Methods iPSC-MSC were treated with LPS and or/Stx for 24 h and secretion of cytokines, adhesion and migration were measured in response to these toxins. Additionally, conditioned media (CM) from treated-iPSC-MSC were collected and used for proteomics analysis and evaluation of endothelial cell healing and tubulogenesis using Human Microvascular Endothelial Cells-1 (HMEC-1) as a source of endothelial cells.Results The results obtained showed that LPS induced a pro-inflammatory profile on iPSC-MSC, whereas Stx effects were less evident, even though cells expressed the Gb3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to a gelatin substrate. Addition of CM of iPSC-MSC treated with LPS + Stx, decreased the capacity of HMEC-1 to close a wound, and did not favor tubulogenesis. Proteomic analysis of iPSC-MSC treated with LPS and/or Stx revealed specific protein secretion patterns that support the functional results described.Conclusions iPSC-MSC activated by LPS acquired a pro-inflammatory profile that induces migration and adhesion to extracellular matrix proteins (ECM) but the addition of Stx did not activate any repair program to ameliorate endothelial damage, indicating that the use of iPSC-MSC to regenerate endothelial injury caused by LPS and/or Stx in HUS could not be the best option to consider to regenerate a tissue injury.