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Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

ABSTRACT: Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective. Graphical Abstract.

SUBMITTER: Ozturk S

PROVIDER: S-EPMC7444453 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

Öztürk Selçuk S Elçin Ayşe Eser AE Koca Ayça A Elçin Yaşar Murat YM

Stem cell reviews and reports 20210401 2

Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have ...[more]

PMID: 32839921

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Project description:Endometrial-derived Mesenchymal Stem Cells (endMSCs) are involved in the regeneration and remodeling of human endometrium, being considered one of the most promising candidates for stem cell-based therapies. Their therapeutic effects have been found to be mediated by extracellular vesicles (EV-endMSCs) with pro-angiogenic, anti-apoptotic, and immunomodulatory effects. Based on that, the main goal of this study was to characterize the proteome and microRNAome of these EV-endMSCs by proteomics and transcriptomics approaches. Additionally, we hypothesized that inflammatory priming of endMSCs may contribute to modify the therapeutic potential of these vesicles. High-throughput proteomics revealed that 617 proteins were functionally annotated as Extracellular exosome (GO:0070062), corresponding to the 70% of the EV-endMSC proteome. Bioinformatics analyses allowed us to identify that these proteins were involved in adaptive/innate immune response, complement activation, antigen processing/presentation, negative regulation of apoptosis, and different signaling pathways, among others. Of note, multiplexed quantitative proteomics and Systems Biology analyses showed that IFNγ priming significantly modulated the protein profile of these vesicles. As expected, proteins involved in antigen processing and presentation were significantly increased. Interestingly, immunomodulatory proteins, such as CSF1, ERAP1, or PYCARD were modified. Regarding miRNAs expression profile in EV-endMSCs, Next-Generation Sequencing (NGS) showed that the preferred site of microRNAome targeting was the nucleus (n = 371 microTargets), significantly affecting signal transduction (GO:0007165), cell proliferation (GO:0008283), and apoptotic processes (GO:0006915), among others. Interestingly, NGS analyses highlighted that several miRNAs, such as hsa-miR-150-5p or hsa-miR-196b-5p, were differentially expressed in IFNγ-primed EV-endMSCs. These miRNAs have a functional involvement in glucocorticoid receptor signaling, IL-6/8/12 signaling, and in the role of macrophages. In summary, these results allowed us to understand the complexity of the molecular networks in EV-endMSCs and their potential effects on target cells. To our knowledge, this is the first comprehensive study based on proteomic and genomic approaches to unravel the therapeutic potential of these extracellular vesicles, that may be used as immunomodulatory effectors in the treatment of inflammatory conditions.

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Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

Publications

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives.

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