Il-1Β Primed Mesenchymal Stromal Cells Moderate Hemorrhagic Shock Induced Organ Injuries

Abstract

BackgroundOrgan damages following hemorrhagic shock (HS) have been partly attributed to an immunological dysfunction. The current challenge in the management of HS patients is to prevent organ injury-induced morbidity and mortality which currently has not etiological treatment available. Mesenchymal stromal cells (MSC) are used in clinical cell therapy for immunomodulation and tissue repair. In vitro priming is often used to improve the immunomodulation efficiency of MSC before administration.ObjectiveAssess the effect of naive MSC (MSCn) or interleukin (IL)-1β primed (MSCp) treatment in a context of HS- induced organ injury.MethodsRats underwent fixed pressure HS and were treated with allogenic MSCn or MSCp. Liver and kidney injuries were evaluated 6h later by histological and biochemical analysis. Whole blood was collected to measure leukocytes phenotypes. Then, in vitro characterization of MSCn or MSCp was carried out.ResultsPlasma Creatinine, blood urea nitrogen and Cystatin C were decrease by MSCp infusion as well as kidney injury molecule (KIM)-1 on histological kidney sections. Transaminases, GGT and liver histology were normalized by MSCp. Systemic cytokines (IL-6 and IL-10) as well as CD80, 86 and PD-1/PDL-1 axis were decreased by MSCp on monocytes and T lymphocytes. In vitro, MSCp showed higher level of secreted immunomodulatory molecules than MSCn.ConclusionAn early administration of MSCp moderates HS-induced kidney and liver injury. IL-1β priming improves MSC efficiency by promoting their immunomodulatory activity. These data provide proof of concept that MSCp could be a therapeutic tool to prevent the appearance of organs injury following HS.

Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

“…The study revealed that the pretreated MSC injections reduced the levels of main organ injury markers including cystatin C, KIM-1, blood urea nitrogen and plasma creatinine. Moreover, the treatment reduced IL-1a, IL-6, IL-10 levels and downregulated the expression of CD80/86, PD-1/PDL-1 by granulocytes and monocytes (86). This indicates that the priming increased the therapeutic effect of MSCs on preventing organ injuries following hemorrhagic shock in vivo.…”

Mesenchymal stem cells and their derived small extracellular vesicles for COVID-19 treatment

“…Yang et al believed that KIM-1 is a potential receptor of SARS-CoV-2, and it mediates and exacerbates the vicious circle of kidney infections by SARS-CoV-2 [49]. Coincidentally, Aussel et al reduced the KIM-1 level on kidney slices by infusion of MSCs [70].…”