Trimetazidine Preconditioning Potentiates the Effect of Mesenchymal Stem Cells Secretome on the Preservation of Rat Pancreatic Islet Survival and Function In Vitro

Ahmadi, Fariborz; Lotfi, Abbas Sahebghadam; Navaei-Nigjeh, Mona; Kadivar, Mehdi

doi:10.1007/s12010-023-04532-8

Cited by 1 publication

(1 citation statement)

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“…In this respect, it was shown that growth factors secreted by MSCs like pro‐angiogenic vascular endothelial growth factor (VEGF) and neuroprotective glial cell‐derived neurotrophic factor (GDNF), neuron growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) have significant therapeutic effects by improving wound healing, tissue repair and survival of neuronal cells respectively (Bai et al, 2016; Guo et al, 2015). Moreover, MSCs‐derived CMs could be effective in treating autoimmune diseases thanks to their immune modulatory contents, including anti‐inflammatory cytokines like IL‐4, IL‐10 (Ahmadi et al, 2023; Doorn et al, 2012; Kay et al, 2017; Konala et al, 2020; Zhang et al, 2019) Extracellular vesicles secreted from MSCs have sizes changing from 30 to 2000 nm and investigated under three subgroups as exosomes, microvesicles, and apoptotic bodies (Kurian et al, 2021). Exosomes, the smallest ECVs with 30–120 μm, contain lipids, proteins, and RNAs.…”

Section: Introductionmentioning

confidence: 99%

Investigation of conditioned medium properties obtained from human umbilical cord mesenchymal stem/stromal cells preconditioned with dimethyloxalylglycine in a correlation with ultrastructural changes

Olcar,

Isildar,

Ozkan

et al. 2023

Microscopy Res & Technique

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Mesenchymal stem/stromal cells (MSCs) hold significant therapeutic value due to their regeneration abilities, migration capacity, and immunosuppressive and immunomodulatory properties. These cells secrete soluble and insoluble factors, and this complex secretome contributes to their therapeutic effect. Furthermore, stimulation of cells by various external stimuli lead to secretome modifications that can increase the therapeutic efficacy. So, this study examined the effect of dimethyloxalylglycine (DMOG), a hypoxia‐mimetic agent, on secretome profiles and exosome secretions of MSCs by evaluating conditioned medium (CM) and ultrastructural morphologies of the cells in comparison with unpreconditioned MSCs. The appropriate dose and duration of the use of DMOG were determined as 1000 μM and 24 h by evaluating the HIF‐1α expression. DMOG‐CM and N‐CM were collected from MSCs incubated in serum‐free medium with/without DMOG for 24 h, respectively. The content analysis of conditioned mediums (CMs) revealed that VEGF, NGF, and IL‐4 levels were increased in DMOG‐CM. Subsequently, exosomes were isolated from the CMs and were shown by transmission electron microscopy and Western blot analysis in both groups. The effects of CMs on proliferation and migration were determined by in vitro wound healing tests; both CMs increased the fibroblast's migratory and proliferative capacities. According to the ultrastructural evaluation, autophagosome, autolysosome, myelin figure, and microvesicular body structures were abundant in DMOG‐preconditioned MSCs. Consistent with the high number of autophagic vacuoles, Beclin‐1 expression was increased in those cells. These findings suggested that DMOG could alter MSCs' secretion profile, modify their ultrastructural morphology accordingly, and make the CM a more potent therapeutic tool.Research Highlights Preconditioning mesenchymal stem/stromal cells with dimethyloxalylglycine, a hypoxia‐mimetic agent, could modify cellular metabolism. Hypoxic mechanisms lead to alterations in the ultrastructural characteristics of mesenchymal stromal/stem cells. Preconditioning with dimethyloxalylglycine leads to ultrastructural and metabolic changes of mesenchymal stromal/stem cells along with modifications in their secretome profiles. Preconditioning of mesenchymal stromal/stem cells could render them a more potent therapeutic tool.

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