Adipose derived mesenchymal stem cell exosomes loaded with miR-10a promote the differentiation of Th17 and Treg from naive CD4+ T cell

Bolandi, Zohreh; Mokhberian, Neda; Eftekhary, Mohamad; Sharifi, Kazem; Soudi, Sara; Ghanbarian, Hossein; Hashemi, Seyed Mahmoud

doi:10.1016/j.lfs.2020.118218

Cited by 71 publications

(47 citation statements)

References 28 publications

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“…Internalization of EVs was also shown to be associated with decreased expression of signal transducer and activator of transcription 1 (STAT1), which has a crucial role in Th1 cell development [48]. Although simultaneous increases in Th17 and Treg by treatment with MSC exosomes have been reported [49], Th17 cells and Tregs are generally considered to be in a competitive relationship. Indeed, MSC exosomes have been reported to promote Tregs while suppressing the polarization of TH17 cells by SphK1-mediated SP1 enrichment in an aplastic anemia (AA) model [50] and increase miR-125a and miR-125b expression in an experimental colitis model [51].…”

Section: Immune-related Diseasesmentioning

confidence: 99%

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Lee

Kang

2021

JCM

115

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Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

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Section: Immune-related Diseasesmentioning

confidence: 99%

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Lee

Kang

2021

JCM

115

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“…Melatonin-stimulated exosomes derived from AD-MSCs can promote M2 macrophage differentiation and exerted superior anti-inflammatory modulation through miRNAs miR-34a, miR-124, and miR-135b [93]. Besides, several in vitro studies have also confirmed the immunosuppression and anti-inflammatory action of MSC-derived exosomes like miR-10a (facilitating Th17 and Treg responses) [94] and IDO (promoting the transformation of mononuclear cells to Tregs) [95]. Therefore, MSC-secreted exosomes exhibit strong immunoregulation effects on cardiac repair and will lay an important basis for the modification and optimization of engineered MSCs for better cardioprotective effects.…”

Section: Limited Inflammationmentioning

confidence: 93%

The Application Potential and Advance of Mesenchymal Stem Cell-Derived Exosomes in Myocardial Infarction

Wang

Tang

Liu

et al. 2021

Stem Cells International

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Myocardial infarction (MI) is a devastating disease with high morbidity and mortality caused by the irreversible loss of functional cardiomyocytes and heart failure (HF) due to the restricted blood supply. Mesenchymal stem cells (MSCs) have been emerging as lead candidates to treat MI and subsequent HF mainly through secreting multitudinous factors of which exosomes act as the most effective constituent to boost the repair of heart function through carrying noncoding RNAs and proteins. Given the advantages of higher stability in the circulation, lower toxicity, and controllable transplantation dosage, exosomes have been described as a wonderful and promising cell-free treatment method in cardiovascular disease. Nowadays, MSC-derived exosomes have been proposed as a promising therapeutic approach to improve cardiac function and reverse heart remodeling. However, exosomes’ lack of modification cannot result in desired therapeutic effect. Hence, optimized exosomes can be developed via various engineering methods such as pharmacological compound preconditioned MSCs, genetically modified MSCs, or miRNA-loaded exosomes and peptide tagged exosomes to improve the targeting and therapeutic effects of exosomes. The biological characteristics, therapeutic potential, and optimizing strategy of exosomes will be described in our review.

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“…Briefly, to every 30 ml of conditioned medium, 6 ml of reagent A was added and vigorously vortexed for 5 min followed by overnight incubation at 4°C with gentle shaking. To pellet sEVs particularly exosomes, the mixture was then centrifuged at 3000 g for 40 min at 4°C (Bolandi et al, 2020). Based on the following experiment, the resulting pellet was resuspended in PBS, RIPA lysis buffer, 2% paraformaldehyde or Trizol reagent.…”

Section: Methodsmentioning

confidence: 99%

Validation of common reference genes stability in exosomal mRNA‐isolated from liver and breast cancer cell lines

Gorji-Bahri

Moradtabrizi

Vakhshiteh

et al. 2021

Cell Biology International

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Accurate relative gene expression analysis by reverse transcription‐quantitative polymerase chain reaction relies on the usage of suitable reference genes for data normalization. The RNA content of small extracellular vesicles including exosomes is growingly considered as cancer biomarkers. So, reliable relative quantification of exosomal messenger RNA (mRNA) is essential for cancer diagnosis and prognosis applications. However, suitable reference genes for accurate normalization of a target gene in exosomes derived from cancer cells are not depicted yet. Here, we analyzed the expression and stability of eight well‐known reference genes namely GAPDH, B2M, HPRT1, ACTB, YWHAZ, UBC, RNA18S, and TBP in exosomes‐isolated from the liver (Huh7, HepG2, PLC/PRF/5) and breast (SK‐BR‐3) cancer cell lines using five different algorithms including geNorm, BestKeeper, Delta Ct, NormFinder, and RefFinder. Our results showed that ACTB, TBP, and HPRT1 were not expressed in exosomes‐isolated from studied liver and breast cancer cell lines. The geNorm and BestKeeper algorithms indicated GAPDH and UBC as the most stable candidates. Moreover, Delta Ct and NormFinder algorithms showed YWHAZ as the most stable reference genes. Comprehensive ranking calculated by the RefFinder algorithm also pointed out GAPDH, YWHAZ, and UBC as the first three stable reference genes. Taken together, this study validated the common reference genes stability in exosomal mRNA derived from liver and breast cancer cell lines for the first time. We believe that this study would be the first step in finding more stable reference genes in exosomes that triggers more accurate detection of exosomal biomarkers.

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Adipose derived mesenchymal stem cell exosomes loaded with miR-10a promote the differentiation of Th17 and Treg from naive CD4+ T cell

Cited by 71 publications

References 28 publications

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

The Application Potential and Advance of Mesenchymal Stem Cell-Derived Exosomes in Myocardial Infarction

Validation of common reference genes stability in exosomal mRNA‐isolated from liver and breast cancer cell lines

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