The potential therapeutic effects of exosomes derived from bone marrow mesenchymal stem cells on ileum injury of a rat sepsis model (histological and immunohistochemical study)

ABSTRACT
Sepsis denotes a serious high mortality concern. The study was designed to evaluate the effect of
mesenchymal stem cell exosomes (MSC-exosomes) on the evolution of the animal model of sepsis.
In this study, 36 rats were distributed into three groups, (I) controls, (II) LPS-treated, and (III) LPS
+MSC-EVs. Sepsis was simulated by administering E. coli-LPS to the laboratory animals. Group III
was given MSC-exosomes four hours after the LPS injection. Forty-eight hours later rats were
sacrificed. Ileum samples were excised, and processed for the histological assessment, immunohistochemical
identification of CD44, and inducible nitric oxide synthase (iNOS). Ileum homogenate
was used to estimate tumor necrosis factor α (TNF α) besides Cyclooxygenase-2 (COX 2). PCR
was used for the detection of interleukin 1α (IL‑1α), and interleukin 17 (IL‑17). Statistical and
morphometrical analysis was done. The LPS-treated group showed increased TNF-α, IL‑1α, IL‑17,
and decreased COX 2. LPS administration led to cytoplasmic vacuolization of enterocytes, an
increase in the vasculature, and cellular infiltrations invaded the lamina propria. There was
a significant rise in goblet cells and the proportion of collagen fibers. Ultrastructurally, the
enterocytes displayed nuclear irregularity, rough endoplasmic reticulum (rER) dilatation, and
increased mitochondria number. Sepsis induces a significant increase in iNOS and a decrease in
CD44 immune expressions. LPS+MSC-EVs group restored normal ileum structure and revealed
a significant elevation in CD44 and a reduction in iNOS immunoreactions. LPS-sepsis induced an
obvious ileum inflammatory deterioration ameliorated by MSC-exosomes, mostly through their
antioxidant, anti-inflammatory, and anti-apoptotic properties.