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      Effects of Lipids and Lipoproteins on Mesenchymal Stem Cells Used in Cardiac Tissue Regeneration

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          Abstract

          Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is quite low; it cannot repair itself after injury, as the heart cells are replaced by fibroblasts and lose function. It is therefore important to search for a feasible way to repair and restore heart function through stem cell therapy. Stem cells can differentiate and provide a source of progenitor cells for cardiomyocytes, endothelial cells, and supporting cells. Studies have shown that the concentrations of blood lipids and lipoproteins affect cardiovascular diseases, such as atherosclerosis, hypertension, and obesity. Furthermore, the MSC lipid profiles, such as the triglyceride and cholesterol content, have been revealed by lipidomics, as well as their correlation with MSC differentiation. Abnormal blood lipids can cause serious damage to internal organs, especially heart tissue. In the past decade, the accumulated literature has indicated that lipids/lipoproteins affect stem cell behavior and biological functions, including their multiple lineage capability, and in turn affect the outcome of regenerative medicine. This review will focus on the effect of lipids/lipoproteins on MSC cardiac regenerative medicine, as well as the effect of lipid-lowering drugs in promoting cardiomyogenesis-associated MSC differentiation.

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          Most cited references69

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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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            Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair.

            Adult mammalian hearts respond to injury with scar formation and not with cardiomyocyte proliferation, the cellular basis of regeneration. Although cardiogenic progenitor cells may maintain myocardial turnover, they do not give rise to a robust regenerative response. Here we show that extracellular periostin induced reentry of differentiated mammalian cardiomyocytes into the cell cycle. Periostin stimulated mononucleated cardiomyocytes to go through the full mitotic cell cycle. Periostin activated alphaV, beta1, beta3 and beta5 integrins located in the cardiomyocyte cell membrane. Activation of phosphatidylinositol-3-OH kinase was required for periostin-induced reentry of cardiomyocytes into the cell cycle and was sufficient for cell-cycle reentry in the absence of periostin. After myocardial infarction, periostin-induced cardiomyocyte cell-cycle reentry and mitosis were associated with improved ventricular remodeling and myocardial function, reduced fibrosis and infarct size, and increased angiogenesis. Thus, periostin and the pathway that it regulates may provide a target for innovative strategies to treat heart failure.
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              Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects.

              A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model. MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-I-labeled MSCs (6 x 10(7)) were implanted into the infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation. Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% +/- 2.2% versus -3.37% +/- 2.7% in control). In addition, the extent of wall thinning after myocardial infarction was markedly reduced in treated animals. Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with myocardial infarction.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                05 July 2020
                July 2020
                : 21
                : 13
                : 4770
                Affiliations
                [1 ]Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; caminolin@ 123456gmail.com (Y.-H.L.); hans0426@ 123456gmail.com (W.-H.F.); k920265@ 123456gap.kmu.edu.tw (W.-C.T.)
                [2 ]Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [3 ]Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
                [4 ]Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [5 ]Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; kanglin@ 123456mail.ncku.edu.tw
                [6 ]Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 801, Taiwan
                [7 ]Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan; junglecc@ 123456gmail.com (T.-L.C.); hthuang@ 123456kmu.edu.tw (H.-T.H.)
                [8 ]Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [9 ]Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [10 ]Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [11 ]Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [12 ]Departments of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [13 ]Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 807, Taiwan
                [14 ]Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
                [15 ]Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804, Taiwan
                Author notes
                [* ]Correspondence: hclee@ 123456kmu.edu.tw (H.-C.L.); hwan@ 123456kmu.edu.tw (C.-H.C.); Tel.: +886-7-3209209 (C.-H.C.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-2232-9037
                https://orcid.org/0000-0002-1994-6205
                https://orcid.org/0000-0001-7080-8652
                https://orcid.org/0000-0002-1123-6954
                https://orcid.org/0000-0002-5877-9059
                https://orcid.org/0000-0001-8941-4792
                Article
                ijms-21-04770
                10.3390/ijms21134770
                7369828
                32635662
                2a9e6e15-2d17-4213-b592-4480939616d0
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 June 2020
                : 03 July 2020
                Categories
                Review

                Molecular biology
                cardiac tissue regeneration,lipid,lipid-lowering drug,lipoprotein,mesenchymal stem cell,simvastatin

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