Do microvesicles derived from adipose mesenchymal stem cells have a therapeutic potential on Escherichia coli lipopolysaccharides-induced sepsis in Zona fasciculata of adult male albino rats? A histological study

Abstract

Introduction: Sepsis is a major health problem with high mortality rate, despite advanced medications. Although hypothalamic-pituitary-adrenal (HPA) axis activation can control its destructive inflammatory reactions, adrenal insufficiency (AI) is commonly associated with it. Mesenchymal Stem Cell-Derived Microvesicles (MSCs-MVs) were proved to be as effective as their origin cells in tissue repair. Aim of the work: To study the effects of Escherichia coli-lipopolysaccharides (E. coli-LPS) induced sepsis on Zona fasciculata of adult male albino rats and probable therapeutic effects of adipose derived mesenchymal stem cells-microvesicles (ADMSCs-MVs). Materials and Methods: Forty-four adult male albino rats were divided into three groups; (I) the controls, (II) LPS and (III) MV. Sepsis was induced in LPS and MV-groups using E. coli-LPS. Four hours later, MV-group received single intravenous (IV) injection of PKH26 labelled ADMSCs-MVs. All animals were sacrificed 48 hours after ADMSCs-MVs administration. Tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nitric oxide (NO) levels were measured in adrenal homogenates of each group. Sections from all groups were subjected to H&E, besides, immunohistochemical stains for CD44, inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen (PCNA). Unstained sections of subgroup IC and MV-group were examined by fluorescent microscope. Mean number of CD44 and PCNA positive cells and mean area percent of iNOS immunoreaction were measured and data were statistically analyzed. Results: LPS-group showed non-survivors (24 hours after LPS-injection) and survivors with features of Zona fasciculata inflammatory damage, besides increased TNF-α and NO and decreased COX-2. The MV-group revealed marked increase in CD44 and PCNA, but significant decrease in iNOS immunoreactions. Additionally, ADMSCs-MV homing was detected in Zona fasciculata. Conclusion: LPS-induced sepsis caused marked Zona fasciculata inflammatory degeneration improved by ADMSCs-MVs single IV injection; mostly through transfer of proteins, mRNA, microRNA and/or organelles with reparative functions from ADMSCs to the injured tissues.