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Immunomodulatory Potential of Human Clonal Mesenchymal Stem Cells and Their Extracellular Vesicle Subpopulations in an Inflammatory-Mediated Diabetic Rhesus Monkey Model Publisher Pubmed



Kashani SA1 ; Navabi R1 ; Amini A1 ; Hajinasrollah M2 ; Jenab Y3 ; Rabbani S3 ; Nazari A1, 4 ; Pakzad M1 ; Moazenchi M1, 4 ; Atrabi MJ1 ; Samsonchi Z1 ; Hezavehei M5 ; Hosseinibeheshti E6, 7 ; Shekari F1, 4 Show All Authors
Authors
  1. Kashani SA1
  2. Navabi R1
  3. Amini A1
  4. Hajinasrollah M2
  5. Jenab Y3
  6. Rabbani S3
  7. Nazari A1, 4
  8. Pakzad M1
  9. Moazenchi M1, 4
  10. Atrabi MJ1
  11. Samsonchi Z1
  12. Hezavehei M5
  13. Hosseinibeheshti E6, 7
  14. Shekari F1, 4
  15. Hajizadehsaffar E4, 8
  16. Baharvand H1, 9
Show Affiliations
Authors Affiliations
  1. 1. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  2. 2. Animal Core Facility, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  3. 3. Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Advanced Therapy Medicinal Product Technology Development Center, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  5. 5. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  6. 6. School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, 2006, NSW, Australia
  7. 7. Sydney Nano Institute, The University of Sydney, Camperdown, 2006, NSW, Australia
  8. 8. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, 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:2023


Abstract

Aims: This study aimed to investigate the therapeutic potential of a homogenous clonal population of mesenchymal stem cells (cMSC) and their extracellular vesicles (cMSC-EV) subpopulations on isolated rat islets in vitro and in inflammatory-mediated type 1 diabetes (T1D) non-human primate models. Main methods: EV subpopulations were isolated from human bone marrow-derived cMSC supernatant by low- and high-speed ultracentrifuge (EV-20K and EV-U110K) and sucrose density gradient (EV-S110K). The EVs were characterized generally and for the level of albumin, acetylcholinesterase (AChE) activity, co-isolate apoptotic markers, and expression of CD63+/annexin V+. Rat islet-derived single cells (iSCs) proliferation was measured using a Ki-67 proliferation assay. Diabetes was induced by multiple low-dose administrations of streptozotocin in rhesus monkeys. The diabetic monkeys were divided into three groups: the cMSC group, received two injections of 1.5 × 106 cMSC/kg body weight; the EV group received two injections of EVs isolated from 1.5 × 106 cMSC/kg, and the vehicle group received phosphate-buffered saline. Key findings: EV-S110K showed higher AChE activity, lower expression of CD63+/annexin V+, and lower apoptotic co-isolates. EV-S110K induced β-cell proliferation in vitro in a dose-dependent manner. The administration of EV-S110K and/or cMSC in diabetic monkeys demonstrated no significant changes in general diabetic indices and β-cell mass in the pancreas of the monkeys. Both treatments demonstrated a lowering trend in blood glucose levels and reduced pro-inflammatory cytokines. In contrast, regulatory T cells and anti-inflammatory cytokines were increased. Significance: cMSC and cMSC-EV provided initial evidence to attenuate clinical symptoms in inflammatory-mediated T1D non-human primates through immunomodulation. © 2023
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