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      Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

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          Abstract

          Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well as their ability to improve tissue regeneration, these cells have attracted the attention of scientists and clinicians for the treatment of different inflammatory and immune system mediated disorders. However, various clinical trials using MSCs for the therapeutic purpose are conflicting and differ from the results of promising preclinical studies. This inconsistency is caused by several factors such as poor migration and homing capacities, low survival rate, low level of proliferation and differentiation, and donor-dependent variation of the cells. Enhancement and retention of persistent therapeutic effects of the cells remain a challenge to overcome in MSC-based therapy. In this review, we summarized various approaches to enhance the clinical outcomes of MSC-based therapy as well as revised current and future perspectives for the creation of cellular products with improved potential for diverse clinical applications.

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          Most cited references195

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          NF-κB signaling in inflammation

          The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.
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            Mechanism and medical implications of mammalian autophagy

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              Biological Functions of Autophagy Genes: A Disease Perspective

              The lysosomal degradation pathway of autophagy plays a fundamental role in cellular, tissue, and organismal homeostasis and is mediated by evolutionarily conserved autophagy-related (ATG) genes. Definitive etiological links exist between mutations in genes that control autophagy and human disease, especially neurodegenerative, inflammatory disorders and cancer. Autophagy selectively targets dysfunctional organelles, intracellular microbes, and pathogenic proteins, and deficiencies in these processes may lead to disease. Moreover, ATG genes have diverse physiologically important roles in other membrane-trafficking and signaling pathways. This Review discusses the biological functions of autophagy genes from the perspective of understanding-and potentially reversing-the pathophysiology of human disease and aging.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 September 2022
                2022
                : 13
                : 1010399
                Affiliations
                [1] 1Department of Medicine, School of Medicine, Nazarbayev University , Nur-Sultan, Kazakhstan
                [2] 2Laboratory of Stem Cells, National Center for Biotechnology , Nur-Sultan, Kazakhstan
                Author notes

                Edited by: Qunzhou Zhang, University of Pennsylvania, United States

                Reviewed by: Scott R. Burks, Clinical Center (NIH), United States; Huanxiang Zhang, Soochow University, China

                *Correspondence: Arman Saparov, asaparov@ 123456nu.edu.kz

                This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.1010399
                9537745
                36211399
                15cffd09-84fd-4c73-b636-cd282168ee70
                Copyright © 2022 Sarsenova, Kim, Raziyeva, Kazybay, Ogay and Saparov

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 August 2022
                : 07 September 2022
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 195, Pages: 22, Words: 12961
                Categories
                Immunology
                Review

                Immunology
                mesenchymal stem cells,cell therapy,preconditioning,cytokines,3d culturing,hypoxia,genetic modifications,immunomodulation

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