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      Controversies regarding transplantation of mesenchymal stem cells

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          Abstract

          Mesenchymal stem cells (MSCs) have tantalized regenerative medicine with their therapeutic potential, yet a cloud of controversies looms over their clinical transplantation. This comprehensive review navigates the intricate landscape of MSC controversies, drawing upon 15 years of clinical experience and research. We delve into the fundamental properties of MSCs, exploring their unique immunomodulatory capabilities and surface markers. The heart of our inquiry lies in the controversial applications of MSC transplantation, including the perennial debate between autologous and allogeneic sources, concerns about efficacy, and lingering safety apprehensions. Moreover, we unravel the enigmatic mechanisms surrounding MSC transplantation, such as homing, integration, and the delicate balance between differentiation and paracrine effects. We also assess the current status of clinical trials and the ever-evolving regulatory landscape. As we peer into the future, we examine emerging trends, envisioning personalized medicine and innovative delivery methods. Our review provides a balanced and informed perspective on the controversies, offering readers a clear understanding of the complexities, challenges, and potential solutions in MSC transplantation.

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          Most cited references87

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          Multilineage potential of adult human mesenchymal stem cells.

          Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.
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            Mesenchymal Stem Cells for Regenerative Medicine

            In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.
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              Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

              The mesenchymal stroma harbors an important population of cells that possess stem cell-like characteristics including self renewal and differentiation capacities and can be derived from a variety of different sources. These multipotent mesenchymal stem cells (MSC) can be found in nearly all tissues and are mostly located in perivascular niches. MSC have migratory abilities and can secrete protective factors and act as a primary matrix for tissue regeneration during inflammation, tissue injuries and certain cancers. These functions underlie the important physiological roles of MSC and underscore a significant potential for the clinical use of distinct populations from the various tissues. MSC derived from different adult (adipose tissue, peripheral blood, bone marrow) and neonatal tissues (particular parts of the placenta and umbilical cord) are therefore compared in this mini-review with respect to their cell biological properties, surface marker expression and proliferative capacities. In addition, several MSC functions including in vitro and in vivo differentiation capacities within a variety of lineages and immune-modulatory properties are highlighted. Differences in the extracellular milieu such as the presence of interacting neighbouring cell populations, exposure to proteases or a hypoxic microenvironment contribute to functional developments within MSC populations originating from different tissues, and intracellular conditions such as the expression levels of certain micro RNAs can additionally balance MSC function and fate.
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                Author and article information

                Contributors
                Journal
                World J Transplant
                WJT
                World Journal of Transplantation
                Baishideng Publishing Group Inc
                2220-3230
                18 June 2024
                18 June 2024
                : 14
                : 2
                : 90554
                Affiliations
                Department of Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
                Department of Genetics, Faculty of Biology, Sofia University St. Kliment Ohridski, Sofia 1164, Bulgaria. dekova@ 123456biofac.uni-sofia.bg
                Department of Genetics, Faculty of Biology, Sofia University St. Kliment Ohridski, Sofia 1164, Bulgaria
                Author notes

                Author contributions: Velikova T and Miteva DG designed the research study, analyzed the data and wrote the manuscript; Velikova T and Dekova T contributed new reagents and analytic tools; Dekova T and Miteva DG performed the research; All authors have read and approve the final manuscript.

                Supported by The National Recovery and Resilience Plan of the Republic of Bulgaria, No. BG-RRP-2.004-0008-C01.

                Corresponding author: Tereza Dekova, PhD, Assistant Professor, Department of Genetics, Faculty of Biology, Sofia University St. Kliment Ohridski, 8 Dragan Tzankov Str, Sofia 1164, Bulgaria. dekova@ 123456biofac.uni-sofia.bg

                Article
                jWJT.v14.i2.eid90554 90554
                10.5500/wjt.v14.i2.90554
                11212595
                4b0a02df-518b-49eb-911d-67ed15f3859a
                ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 18 December 2023
                : 7 February 2024
                : 3 April 2024
                Categories
                Minireviews

                mesenchymal stem cells,transplantation controversies,regenerative medicine,autoimmune diseases,chronic inflammatory illnesses,tumor growth,metastasis,therapeutic potential,clinical use of mesenchymal stem cell

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