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

MARTIRE GRECO D; LA GRECA A; CASTILLO LA,; BIANI C; LOMBARDI A; BIRNBERG WEISS F; NORRIS A; SACERDOTTI F; AMARAL MM; RODRIGUEZ-RODRIGUES N; PITTALUGA VILLARREAL JR; FURMENTO VA; VERONICA IL; MIRIUKA S; LUZZANI C; FERNÁNDEZ G C

SHOCK

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2023

1073-2322

Background: Mesenchymal Stem Cells (MSC) can be activated by different bacterialtoxins. Lipopolysaccharides (LPS) and Shiga Toxin (Stx) are the main toxinsnecessary for Hemolytic Uremic Syndrome (HUS) development. The mainetiological event in this disease is endothelial damage that causes glomerulardestruction. Considering the repairing properties of MSC we aimed to study theresponse of MSC derived from induced Pluripotent Stem Cells (iPSC-MSC) to LPSand/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 ofcytokines, adhesion and migration were measured in response to these toxins.Additionally, conditioned media (CM) from treated-iPSC-MSC were collected andused for proteomics analysis and evaluation of endothelial cell healing andtubulogenesis using Human Microvascular Endothelial Cells-1 (HMEC-1) as asource of endothelial cells.Results: The results obtained showed that LPS induced a pro-inflammatory profileon iPSC-MSC, whereas Stx effects were less evident, even though cells expressedthe Gb3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migrationand adhesion to a gelatin substrate. Addition of CM of iPSC-MSC treated withLPS+Stx, decreased the capacity of HMEC-1 to close a wound, and did not favortubulogenesis. Proteomic analysis of iPSC-MSC treated with LPS and/or Stxrevealed specific protein secretion patterns that support the functional resultsdescribed.Conclusions: iPSC-MSC activated by LPS acquired a pro-inflammatory profile thatinduces migration and adhesion to extracellular matrix proteins (ECM) but theaddition of Stx did not activate any repair program to ameliorate endothelialdamage, indicating that the use of iPSC-MSC to regenerate endothelial injurycaused by LPS and/or Stx in HUS could not be the best option to consider toregenerate a tissue injury.