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Combined Therapy of Mesenchymal Stem Cells With a Glp-1 Receptor Agonist, Liraglutide, on an Inflammatory-Mediated Diabetic Non-Human Primate Model Publisher Pubmed



Navabi R1, 2 ; Negahdari B1 ; Hajizadehsaffar E2, 3, 4 ; Hajinasrollah M5 ; Jenab Y6 ; Rabbani S6 ; Pakzad M7 ; Hassani SN3, 7 ; Hezavehei M8 ; Jafariatrabi M7 ; Tahamtani Y4, 7 ; Baharvand H7, 9
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  3. 3. Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  4. 4. Department of Diabetes, Obesity, and Metabolism, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  5. 5. Animal Core Facility, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  6. 6. Tehran Heart Center, Tehran University of Medical Science, Tehran, Iran
  7. 7. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  8. 8. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  9. 9. Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran

Source: Life Sciences Published:2021


Abstract

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. © 2021