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      Mesenchymal stem cell perspective: cell biology to clinical progress

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          Abstract

          The terms MSC and MSCs have become the preferred acronym to describe a cell and a cell population of multipotential stem/progenitor cells commonly referred to as mesenchymal stem cells, multipotential stromal cells, mesenchymal stromal cells, and mesenchymal progenitor cells. The MSCs can differentiate to important lineages under defined conditions in vitro and in limited situations after implantation in vivo. MSCs were isolated and described about 30 years ago and now there are over 55,000 publications on MSCs readily available. Here, we have focused on human MSCs whenever possible. The MSCs have broad anti-inflammatory and immune-modulatory properties. At present, these provide the greatest focus of human MSCs in clinical testing; however, the properties of cultured MSCs in vitro suggest they can have broader applications. The medical utility of MSCs continues to be investigated in over 950 clinical trials. There has been much progress in understanding MSCs over the years, and there is a strong foundation for future scientific research and clinical applications, but also some important questions remain to be answered. Developing further methods to understand and unlock MSC potential through intracellular and intercellular signaling, biomedical engineering, delivery methods and patient selection should all provide substantial advancements in the coming years and greater clinical opportunities. The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.

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          Most cited references88

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          Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.

          Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO2, Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P < .001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. clinicaltrials.gov Identifier: NCT01087996.
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            THE DEVELOPMENT OF FIBROBLAST COLONIES IN MONOLAYER CULTURES OF GUINEA-PIG BONE MARROW AND SPLEEN CELLS

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              The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells.

                Author and article information

                Contributors
                mfpittenger@comcast.net
                bpeault@mednet.ucla.edu
                Journal
                NPJ Regen Med
                NPJ Regen Med
                NPJ Regenerative Medicine
                Nature Publishing Group UK (London )
                2057-3995
                2 December 2019
                2 December 2019
                2019
                : 4
                : 22
                Affiliations
                [1 ]ISNI 0000 0001 2175 4264, GRID grid.411024.2, Department of Surgery, , University of Maryland School of Medicine, ; 10S. Pine Street, Baltimore, MD 21212 USA
                [2 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Biophysical Engineering Labs, , University of Pennsylvania, ; 129 Towne Bldg, Philadelphia, PA 19104-6393 USA
                [3 ]ISNI 0000 0000 9632 6718, GRID grid.19006.3e, Orthopedic Hospital Research Center, , UCLA/Orthopedic Surgery, ; 615 Charles E. Young Drive, Los Angeles, CA 90095 USA
                [4 ]ISNI 0000 0004 1936 7988, GRID grid.4305.2, MRC Centre for Regenerative Medicine, , University of Edinburgh, ; 5 Little France Drive, Edinburgh, EH16 4UU UK
                [5 ]ISNI 0000000122199231, GRID grid.214007.0, Department of Molecular Medicine, A231, , The Scripps Research Institute, ; 130 Scripps Way, Jupiter, FL 33458 USA
                [6 ]ISNI 0000 0004 1936 8606, GRID grid.26790.3a, Interdisciplinary Stem Cell Institute, , University of Miami Miller School of Medicine, ; Biomedical Research Building/Room 908, PO Box 016960 (R-125), Miami, FL 33101 USA
                [7 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Department of Biology and Skeletal Research Center, , Case-Western University, ; Millis Science Center, Room 118, 10900 Euclid Ave, Cleveland, OH 44106 USA
                Author information
                http://orcid.org/0000-0003-2744-1765
                http://orcid.org/0000-0002-8688-2619
                Article
                83
                10.1038/s41536-019-0083-6
                6889290
                31815001
                7026811c-8aba-48f9-ae67-8e0f2a3cc996
                © The Author(s) 2019

                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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 January 2019
                : 20 September 2019
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2019

                mesenchymal stem cells,stem-cell research
                mesenchymal stem cells, stem-cell research

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