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Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation.

ABSTRACT: The immunosuppressive potential of mesenchymal stem cells has been extensively investigated in many studies in vivo and in vitro. In recent years, a variety preclinical and clinical studies have demonstrated that mesenchymal stem cells ameliorate immune-mediated disorders, including autoimmune diseases. However, to date mesenchymal stem cells have not become a widely used therapeutic agent due to safety challenges, high cost and difficulties in providing long term production. A key mechanism underpinning the immunomodulatory effect of MSCs is the production of paracrine factors including growth factors, cytokines, chemokines, and extracellular vesicles (EVs). MSCs derived EVs have become an attractive therapeutic agent for immunomodulation and treatment of immune-mediated disorders. In addition to many preclinical studies of MSCs derived EVs, their beneficial effects have been observed in patients with both acute graft-vs.-host disease and chronic kidney disease. In this review, we discuss the current findings in the field of MSCs derived EVs-based therapies in immune-mediated disorders and approaches to scale EV production for clinical use.

SUBMITTER: Gomzikova MO

PROVIDER: S-EPMC6889906 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation.

Gomzikova Marina O MO James Victoria V Rizvanov Albert A AA

Frontiers in immunology 20191115

The immunosuppressive potential of mesenchymal stem cells has been extensively investigated in many studies <i>in vivo</i> and <i>in vitro</i>. In recent years, a variety preclinical and clinical studies have demonstrated that mesenchymal stem cells ameliorate immune-mediated disorders, including autoimmune diseases. However, to date mesenchymal stem cells have not become a widely used therapeutic agent due to safety challenges, high cost and difficulties in providing long term production. A key ...[more]

PMID: 31849929

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Project description:BackgroundRetinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic.MethodsTo overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa.ResultsT-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dose-dependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat.ConclusionsTogether, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Dataset Information

Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation.

Publications

Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation.

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