Combined therapy of mesenchymal stem cells with a GLP-1 receptor agonist, liraglutide, on an inflammatory-mediated diabetic non-human primate model
| Autor: | Seyedeh-Nafiseh Hassani, Ensiyeh Hajizadeh-Saffar, Maryam Hezavehei, Roghayeh Navabi, Mohamad Pakzad, Mostafa Hajinasrollah, Mohammad Jafari-Atrabi, Babak Negahdari, Hossein Baharvand, Shahram Rabbani, Yaser Jenab, Yaser Tahamtani |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Agonist Combination therapy medicine.drug_class Pharmacology Mesenchymal Stem Cell Transplantation Glucagon-Like Peptide-1 Receptor General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Diabetes mellitus medicine Animals Hypoglycemic Agents General Pharmacology Toxicology and Pharmaceutics Glucagon-like peptide 1 receptor Inflammation Type 1 diabetes Liraglutide business.industry Mesenchymal stem cell Mesenchymal Stem Cells General Medicine medicine.disease Streptozotocin Combined Modality Therapy Macaca mulatta Female business medicine.drug |
| Zdroj: | Life Sciences. 276:119374 |
| ISSN: | 0024-3205 |
| Popis: | Aims Immunomodulation concurrent with the promotion of β-cell function is a strategy used to develop innovative therapies for type 1 diabetes (T1D). Here, we assessed the therapeutic potential of co-administration of human clonal mesenchymal stem (stromal) cells (hBM-cMSCs) and liraglutide as a glucagon-like peptide-1 agonist in a non-human primate model with streptozotocin (STZ)-induced diabetes. Main methods Diabetes was induced through intravenous (i.v.) multiple low-dose (MLD) infusions of STZ at a dose of 30 mg/kg body weight (b.w.) for five consecutive days, followed by two booster injections of 35 mg/kg on days 12 and 19. After 90 days, the diabetic animals were randomly allocated to two groups: The combination therapy group (n = 4) received injections of 1.5 × 106 hBM-cMSCs/kg b.w. through celiac artery by angiography on days 91 and 105 and daily subcutaneous injections of liraglutide (up to 1.8 mg/day) until day 160 while vehicle group received phosphate-buffered saline. The monkeys were assessed for functional, immunological, and histological analysis. Key findings The combined treatment group had continued reduction in FBG levels up to day 160, which was accompanied by increased b.w., C-peptide, and β-cell function, and decreased HbA1c and fructosamine levels compared to vehicle group. The combined treatment increased Tregs, IL-4, IL-10, and TGF-β1 and decreased IL-6 and IL-1β. Stereological analysis of the pancreatic tissue exhibited more total volume of insulin-secreting islets in the combined treatment group compared to vehicle group. Significance Our findings demonstrated this combined treatment impaired the clinical symptoms of diabetes in this animal model through immunomodulation and β-cell preservation. |
| Databáze: | OpenAIRE |
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