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      AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats.

      1 , 1 , 2 , 3 , 2 , 4 , 5 , 6
      Saudi journal of biological sciences
      Elsevier BV
      AD-MSCs, Adipose-derived mesenchymal stem cells, AGEs, Advanced glycation end products, ALP, Alkaline phosphatase, ALT, Alanine aminotransferase, AST, Aspartate aminotransferase, BM-MSCs, Bone marrow-derived mesenchymal stem cells, BUN, Blood urea nitrogen, CD, Cluster of differentiation, D, Diabetic, DM, Diabetes mellitus, DMEM, Dulbecco's modified Eagle's medium, DN, Diabetic nephropathy, Diabetes, Diabetic nephropathy, FBG, Fasting blood glucose, FBS, Fetal bovine serum, HDL-C, High-density lipoprotein cholesterol, HO-1, Heme-oxygenase 1, HbA1c, Glycosylated hemoglobin, Hyperlipidemia, IPCs, Insulin producing cells, ISCT, International Society for Cellular Therapy, LDL-C, Low-density lipoprotein cholesterol, LPO, Lipid peroxidation, MSCs, MSCs, Mesenchymal stem cells, PBS, Phosphate-buffered saline, ROS, Reactive oxygen species, SEM, Standard error of mean, SPSS, Statistical Package for Social Scientists, STZ, Streptozotocin, T1DM, Type 1 diabetes mellitus, TC, Total cholesterol, TG, Triglycerides, TL, Total lipids, γ-GT, gamma glutamyl transferase

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          Abstract

          Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

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          Most cited references54

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          Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide.

          In this direct colorimetric procedure, serum triglycerides are hydrolyzed by lipase, and the released glycerol is assayed in a reaction catalyzed by glycerol kinase and L-alpha-glycerol-phosphate oxidase in a system that generates hydrogen peroxide. The hydrogen peroxide is monitored in the presence of horseradish peroxidase with 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone as the chromogenic system. The high absorbance of this chromogen system at 510 nm affords useful results with a sample/reagent volume ratio as low as 1:150, and a blank sample measurement is not needed. A single, stable working reagent is used; the reaction is complete in 15 min at room temperature. The standard curve is linear for triglyceride concentrations as great as 13.6 mmol/L. Average analytical recovery of triglycerides in human sera is 100.1%, and within-run and between-run precision studies showed CVs of less than or equal to 1.6 and less than or equal to 3.0%, respectively. The method is suitable for automation.
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            Immune Regulatory Properties of Allogeneic Adipose-Derived Mesenchymal Stem Cells in the Treatment of Experimental Autoimmune Diabetes

            Adipose-derived mesenchymal stem cells (ADMSCs) display immunosuppressive properties, suggesting a promising therapeutic application in several autoimmune diseases, but their role in type 1 diabetes (T1D) remains largely unexplored. The aim of this study was to investigate the immune regulatory properties of allogeneic ADMSC therapy in T cell–mediated autoimmune diabetes in NOD mice. ADMSC treatment reversed the hyperglycemia of early-onset diabetes in 78% of diabetic NOD mice, and this effect was associated with higher serum insulin, amylin, and glucagon-like peptide 1 levels compared with untreated controls. This improved outcome was associated with downregulation of the CD4+ Th1-biased immune response and expansion of regulatory T cells (Tregs) in the pancreatic lymph nodes. Within the pancreas, inflammatory cell infiltration and interferon-γ levels were reduced, while insulin, pancreatic duodenal homeobox-1, and active transforming growth factor-β1 expression were increased. In vitro, ADMSCs induced the expansion/proliferation of Tregs in a cell contact–dependent manner mediated by programmed death ligand 1. In summary, ADMSC therapy efficiently ameliorates autoimmune diabetes pathogenesis in diabetic NOD mice by attenuating the Th1 immune response concomitant with the expansion/proliferation of Tregs, thereby contributing to the maintenance of functional β-cells. Thus, this study may provide a new perspective for the development of ADMSC-based cellular therapies for T1D.
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              Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow-derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus.

              Stem cell therapy (SCT) is now the up-coming therapeutic modality for treatment of type 1 diabetes mellitus (T1DM).
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                Author and article information

                Journal
                Saudi J Biol Sci
                Saudi journal of biological sciences
                Elsevier BV
                1319-562X
                2213-7106
                Feb 2022
                : 29
                : 2
                Affiliations
                [1 ] Zoology Department, Faculty of Science, Arish University, North Sinai, Egypt.
                [2 ] Biotechnology Department, Faculty of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
                [3 ] Clinical Laboratory Science Department, Turabah University College, Taif University, Taif 21995, Saudi Arabia.
                [4 ] Fellow of Biochemistry, Genetic Unit, Children Hospital, Faculty of Medicine, Mansoura University, Egypt.
                [5 ] Biology Department, Faculty of Science, Taif University, Saudi Arabia.
                [6 ] Biology Department, College of Science, University of Bisha, Bisha 61922, P.O. Box 344, Saudi Arabia.
                Article
                S1319-562X(21)00871-8
                10.1016/j.sjbs.2021.09.067
                8847940
                35197774
                2fb0dcd4-9179-4bd5-80bd-3a66fab2dbaa
                History

                IPCs, Insulin producing cells,ALT, Alanine aminotransferase,AST, Aspartate aminotransferase,BM-MSCs, Bone marrow-derived mesenchymal stem cells,BUN, Blood urea nitrogen,CD, Cluster of differentiation,D, Diabetic,DM, Diabetes mellitus,DMEM, Dulbecco's modified Eagle's medium,DN, Diabetic nephropathy,Diabetes,Diabetic nephropathy,FBG, Fasting blood glucose,FBS, Fetal bovine serum,HDL-C, High-density lipoprotein cholesterol,HO-1, Heme-oxygenase 1,HbA1c, Glycosylated hemoglobin,Hyperlipidemia,ISCT, International Society for Cellular Therapy,LDL-C, Low-density lipoprotein cholesterol,LPO, Lipid peroxidation,MSCs,MSCs, Mesenchymal stem cells,PBS, Phosphate-buffered saline,ROS, Reactive oxygen species,SEM, Standard error of mean,SPSS, Statistical Package for Social Scientists,STZ, Streptozotocin,T1DM, Type 1 diabetes mellitus,TC, Total cholesterol,TG, Triglycerides,TL, Total lipids,γ-GT, gamma glutamyl transferase,AD-MSCs, Adipose-derived mesenchymal stem cells,AGEs, Advanced glycation end products,ALP, Alkaline phosphatase

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