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.

KEYWORDS:

• CD44
• COX2
• LPS
• MSC-exosomes
• Sepsis
• TNFα

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions statement

Conceptualization, Heba Elnegris; Methodology, Heba Elnegris; Formal analysis, Eman S El-Roghy., Heba M Elnegris., Abeer ali Abdel Rahman; Investigation, Heba M Elnegris., Abeer ali Abdel Rahman; writing-original draft preparation; Heba M Elnegris, Eman S El-Roghy, Abeer ali Abdel Rahman; writing – review and editing, Heba M Elnegris, Eman S El-Roghy, Abeer ali Abdel Rahman; visualization, Heba M Elnegris, Eman S El-Roghy; supervision, Heba M Elnegris. All authors have read and agreed to the published version of the manuscript.

Ethical approval

Institutional Review Board Statement: The study was conducted according to the guidelines of the Institutional Animal Care and Use Committee and approved by ZU-IACUC at Zagazig University (code number: ZU-IACUC/3/F/214/2023; date of approval: 22 June 2023).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.