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      Glial-restricted progenitor cells: a cure for diseased brain?

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          Abstract

          The central nervous system (CNS) is home to neuronal and glial cells. Traditionally, glia was disregarded as just the structural support across the brain and spinal cord, in striking contrast to neurons, always considered critical players in CNS functioning. In modern times this outdated dogma is continuously repelled by new evidence unravelling the importance of glia in neuronal maintenance and function. Therefore, glia replacement has been considered a potentially powerful therapeutic strategy. Glial progenitors are at the center of this hope, as they are the source of new glial cells. Indeed, sophisticated experimental therapies and exciting clinical trials shed light on the utility of exogenous glia in disease treatment. Therefore, this review article will elaborate on glial-restricted progenitor cells (GRPs), their origin and characteristics, available sources, and adaptation to current therapeutic approaches aimed at various CNS diseases, with particular attention paid to myelin-related disorders with a focus on recent progress and emerging concepts. The landscape of GRP clinical applications is also comprehensively presented, and future perspectives on promising, GRP-based therapeutic strategies for brain and spinal cord diseases are described in detail.

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          Most cited references192

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

            The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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              Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

              Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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                Author and article information

                Contributors
                lstanaszek@imdik.pan.pl
                Journal
                Biol Res
                Biol Res
                Biological Research
                BioMed Central (London )
                0716-9760
                0717-6287
                12 March 2024
                12 March 2024
                2024
                : 57
                : 8
                Affiliations
                [1 ]GRID grid.413454.3, ISNI 0000 0001 1958 0162, NeuroRepair Department, , Mossakowski Medical Research Institute, Polish Academy of Sciences, ; 02-106 Warsaw, Poland
                [2 ]Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, ( https://ror.org/04rq5mt64) Baltimore, MD USA
                Author information
                http://orcid.org/0000-0003-3205-5949
                Article
                486
                10.1186/s40659-024-00486-1
                10935984
                38475854
                b87836d4-c3f4-4455-84e0-8c3b31d5234b
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 3 March 2023
                : 26 February 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005632, Narodowe Centrum Badań i Rozwoju;
                Award ID: 1/233209/12/NCBR/2015 “GRP&ALS”
                Award ID: 12/EuroNanoMed/2016
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004281, Narodowe Centrum Nauki;
                Award ID: SONATA 2017/26/D/NZ3/00721
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004895, European Social Fund;
                Award ID: POWR.03.02.00-00-I028/17-00
                Award Recipient :
                Funded by: the National Science Centre grant
                Award ID: SONATA 2017/26/D/NZ3/00721
                Categories
                Review
                Custom metadata
                © Sociedad de Biologia de Chile 2024

                glial-restricted progenitor,oligodendrocyte precursor cell,oligodendrocyte,myelin,pre-clinical study,cell therapy

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