The objective of our study was to evaluate the therapeutic potential of bone marrow mesenchymal stromal cells (MSC) in a rat model of severe chronic liver injury. Fourteen female Wistar rats were fed exclusively an alcoholic liquid diet and received intraperitoneal injections of carbon tetrachloride every other day during 15 weeks. After this period, eight animals (MSC group) had 1 ؋ 10 7 cells injected into the portal vein while six animals (placebo group) received vehicle. Blood analysis was performed to evaluate alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin before cell therapy and 1 and 2 months after cell or placebo infusion. Fibrosis was evaluated before and 1 month after cell or placebo injection by liver biopsies. Two months after cell delivery, animals were sacrificed and histological analysis of the livers was performed. Fibrosis was quantified by histomorphometry. Biopsies obtained before cell infusion showed intense collagen deposition and septa interconnecting regenerative nodules. One month after cell injection, this result was unaltered and differences in fibrosis quantification were not found between MSC and placebo groups. ALT and AST returned to normal values 2 weeks after cell or placebo infusion, without significant differences between experimental groups. Two months after cell or placebo injection, albumin had also returned to normal values and histological results were maintained, again without differences between MSC and placebo groups. Therefore, under our experimental conditions, MSC were unable to reduce fibrosis or improve liver function in a rat model of severe chronic liver injury.
Bone marrow-derived mononuclear cells from ARDSp and ARDSexp donors showed different characteristics but were as effective as cells obtained from healthy donors in reducing inflammation and remodeling, suggesting the utility of autologous transplant of bone marrow-derived mononuclear cells in the clinical setting.
BAI was associated with emerging CV risk markers in adolescents but further research is needed to evaluate its potential in clinical and epidemiological sets.
BackgroundDiabetes mellitus is a severe chronic disease leading to systemic
complications, including cardiovascular dysfunction. Previous cell therapy
studies have obtained promising results with the use bone marrow mesenchymal
stromal cells derived from healthy animals (MSCc) in diabetes animal models.
However, the ability of MSC derived from diabetic rats to improve functional
cardiac parameters is still unknown.ObjectivesTo investigate whether bone-marrow-derived MSC from diabetic rats (MSCd)
would contribute to recover metabolic and cardiac electrical properties in
other diabetic rats.MethodsDiabetes was induced in Wistar rats with streptozotocin. MSCs were
characterized by flow cytometry, morphological analysis, and
immunohistochemistry. Cardiac electrical function was analyzed using
recordings of ventricular action potential. Differences between variables
were considered significant when p < 0.05.ResultsIn vitro properties of MSCc and MSCd were evaluated. Both cell types
presented similar morphology, growth kinetics, and mesenchymal profile, and
could differentiate into adipogenic and osteogenic lineages. However, in an
assay for fibroblast colony-forming units (CFU-F), MSCd formed more colonies
than MSCc when cultured in expansion medium with or without hydrocortisone
(1 µM). In order to compare the therapeutic potential of the cells,
the animals were divided into four experimental groups: nondiabetic (CTRL),
diabetic (DM), diabetic treated with MSCc (DM + MSCc), and diabetic treated
with MSCd (DM + MSCd). The treated groups received a single injection of MSC
4 weeks after the development of diabetes. MSCc and MSCd controlled
hyperglycemia and body weight loss and improved cardiac electrical
remodeling in diabetic rats.ConclusionsMSCd and MSCc have similar in vitro properties and therapeutic potential in a
rat model of diabetes induced with streptozotocin.
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