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      Stem cell therapy for heart failure in the clinics: new perspectives in the era of precision medicine and artificial intelligence

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          Abstract

          Stem/progenitor cells have been widely evaluated as a promising therapeutic option for heart failure (HF). Numerous clinical trials with stem/progenitor cell-based therapy (SCT) for HF have demonstrated encouraging results, but not without limitations or discrepancies. Recent technological advancements in multiomics, bioinformatics, precision medicine, artificial intelligence (AI), and machine learning (ML) provide new approaches and insights for stem cell research and therapeutic development. Integration of these new technologies into stem/progenitor cell therapy for HF may help address: 1) the technical challenges to obtain reliable and high-quality therapeutic precursor cells, 2) the discrepancies between preclinical and clinical studies, and 3) the personalized selection of optimal therapeutic cell types/populations for individual patients in the context of precision medicine. This review summarizes the current status of SCT for HF in clinics and provides new perspectives on the development of computation-aided SCT in the era of precision medicine and AI/ML.

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          Most cited references145

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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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              Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association

              Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. Results: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. Conclusions: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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                Author and article information

                Contributors
                Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2250493/overviewRole: Role: Role:
                Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1761084/overviewRole: Role: Role: Role: Role: Role: Role: Role: Role:
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                09 January 2024
                2023
                : 14
                : 1344885
                Affiliations
                [1] 1 Division of Basic Biomedical Sciences , Sanford School of Medicine , University of South Dakota , Vermillion, SD, United States
                [2] 2 Department of Public Health and Health Sciences , Health Sciences Ph.D. Program , School of Health Sciences , University of South Dakota , Vermillion, SD, United States
                [3] 3 Department of Cardiology , North Central Heart , Avera Heart Hospital , Sioux Falls, SD, United States
                [4] 4 Department of Computer Science , University of South Dakota , Vermillion, SD, United States
                Author notes

                Edited by: Meijing Wang, Indiana University Bloomington, United States

                Reviewed by: Jia Yao, Emory University, United States

                Wei Jaing, Sichuan University, China

                *Correspondence: William C. W. Chen, William.Chen@ 123456usd.edu
                Article
                1344885
                10.3389/fphys.2023.1344885
                10803627
                38264333
                af0ccb8f-54e4-4818-821b-a4c25957dca4
                Copyright © 2024 Chowdhury, Zhang, Rizk and Chen.

                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
                : 26 November 2023
                : 26 December 2023
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the U.S. Department of Defense (W81XWH2110089 to WC), the American Heart Association Career Development Award (855260 to WC), and the University of South Dakota Sanford School of Medicine (Startup Fund to WC).
                Categories
                Physiology
                Mini Review
                Custom metadata
                Clinical and Translational Physiology

                Anatomy & Physiology
                stem cells,heart failure,cell therapy,precision medicine,artificial intelligence,machine learning,clinical trial,regenerative medicine

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