Immunomodulatory potential of human clonal mesenchymal stem cells and their extracellular vesicle subpopulations in an inflammatory-mediated diabetic Rhesus monkey model
Copyright © 2023. Published by Elsevier Inc..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:329 |
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| Enthalten in: |
Life sciences - 329(2023) vom: 15. Sept., Seite 121950 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kashani, Sara Assar [VerfasserIn] |
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| Links: |
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| Themen: |
Acetylcholinesterase |
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| Anmerkungen: |
Date Completed 14.08.2023 Date Revised 14.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.lfs.2023.121950 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Kashani, Sara Assar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Immunomodulatory potential of human clonal mesenchymal stem cells and their extracellular vesicle subpopulations in an inflammatory-mediated diabetic Rhesus monkey model |
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| 500 | |a Date Revised 14.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a SIGNIFICANCE: cMSC and cMSC-EV provided initial evidence to attenuate clinical symptoms in inflammatory-mediated T1D non-human primates through immunomodulation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Clonal mesenchymal stem cells | |
| 650 | 4 | |a Extracellular vesicles | |
| 650 | 4 | |a Immunomodulation | |
| 650 | 4 | |a Non- human primate | |
| 650 | 4 | |a Type 1 diabetes | |
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| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Immunologic Factors |2 NLM | |
| 700 | 1 | |a Navabi, Roghayeh |e verfasserin |4 aut | |
| 700 | 1 | |a Amini, Azadeh |e verfasserin |4 aut | |
| 700 | 1 | |a Hajinasrollah, Mostafa |e verfasserin |4 aut | |
| 700 | 1 | |a Jenab, Yaser |e verfasserin |4 aut | |
| 700 | 1 | |a Rabbani, Shahram |e verfasserin |4 aut | |
| 700 | 1 | |a Nazari, Abdoreza |e verfasserin |4 aut | |
| 700 | 1 | |a Pakzad, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Moazenchi, Maedeh |e verfasserin |4 aut | |
| 700 | 1 | |a Atrabi, Mohammad Jafari |e verfasserin |4 aut | |
| 700 | 1 | |a Samsonchi, Zakieh |e verfasserin |4 aut | |
| 700 | 1 | |a Hezavehei, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Hosseini-Beheshti, Elham |e verfasserin |4 aut | |
| 700 | 1 | |a Shekari, Faezeh |e verfasserin |4 aut | |
| 700 | 1 | |a Hajizadeh-Saffar, Ensiyeh |e verfasserin |4 aut | |
| 700 | 1 | |a Baharvand, Hossein |e verfasserin |4 aut | |
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