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Background: Mesenchymal stem cells (MSCs) can be activated by different bacterial toxins. Lipopolysaccharides and Shiga Toxin (Stx) are the main toxins necessary for hemolytic uremic syndrome 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. In addition, conditioned media 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 as a source of endothelial cells. Results: The results obtained showed that LPS induced a proinflammatory profile on iPSC-MSC, whereas Stx effects were less evident, even though cells expressed the Gb3receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to a gelatin substrate. Addition of conditioned media of iPSC-MSC treated with LPS + Stx, decreased the capacity of human microvascular endothelial cells 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 proinflammatory profile that induces migration and adhesion to extracellular matrix proteins 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 hemolytic uremic syndrome could not be the best option to consider to regenerate a tissue injury.

Shiga toxin (Stx) is the main virulence factor of Stx-producing Escherichia coli, a pathogen responsible for developing Hemolytic Uremic Syndrome. Nowadays, no specific treatment exists for this disease, and nanomicelles may be an excellent platform for the delivery of specific compounds, including immunoglobulins (IgG), for therapeutic or diagnostic strategies. In this work, Soluplus® nanomicelles (NM) were associated with IgG against Stx type 2 (NM-IgG-Stx2). Physicochemical evaluation of NM-IgG-Stx2 was performed by Dynamic Light Scattering, Uv–Vis, Fluorescence, and Circular Dichroism spectroscopy. Morphology was analyzed by transmission electron microscopy. An in silicoanalysis of NM-IgG-Stx2 association was performed, and neutralization properties against purified Stx2 and Stx-derived supernatants were analyzed on Vero and HGEC cells. Our results suggest that IgG-Stx2 assemble with NM, and the interaction improves the Stx2 neutralization capacity of the antibody. These results suggest that NM may enhance IgG-Stx2 paratope availability and may be an excellent platform for the recognition and neutralization of Stx2.

•Fifty-one percent of teachers had circulating antibodies against O157, O145, O121 and O103 LPS.•Anti-O157 antibodies were the most abundant found in 43% of the samples.•Twenty-one of the samples reacted against more than one LPS serotype.•Twenty percent showed IgM antibodies against at least one LPS serotype.•Continuous educational programs could help to reduce cases of HUS.