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      The potential and challenges of using stem cells for cardiovascular repair and regeneration

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          Abstract

          Recent progress in using stem cells for tissue repair and functional restoration has aroused much attention due to its potential to provide a cue for many diseases such as myocardial infarction. Stem cell therapy for cardiovascular disease has been studied extensively at both experimental and clinical levels. Pluripotent stem cells and mesenchymal stem cells were proven to be effective for myocardial regeneration, angiogenesis, and cardiac functional restoration. In this review, we will concisely discuss advantages and disadvantages of currently-used stem cells for cardiovascular repair and regeneration. The limitations and uniqueness of some types of stem cells will also be discussed. Although substantial progress has been made over the last decade about stem cells in cardiovascular regeneration, many challenges lie ahead before the therapeutic potentials of stem cells can be fully recognized.

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          Establishment in culture of pluripotential cells from mouse embryos.

          Sydney M. Evans, H Kaufman (1981)
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            Endothelial progenitor cells: characterization and role in vascular biology.

            Carmen Urbich, Stefanie Dimmeler (2004)
            Infusion of different hematopoietic stem cell populations and ex vivo expanded endothelial progenitor cells augments neovascularization of tissue after ischemia and contributes to reendothelialization after endothelial injury, thereby, providing a novel therapeutic option. However, controversy exists with respect to the identification and the origin of endothelial progenitor cells. Overall, there is consensus that endothelial progenitor cells can derive from the bone marrow and that CD133/VEGFR2 cells represent a population with endothelial progenitor capacity. However, increasing evidence suggests that there are additional bone marrow-derived cell populations (eg, myeloid cells, "side population" cells, and mesenchymal cells) and non-bone marrow-derived cells, which also can give rise to endothelial cells. The characterization of the different progenitor cell populations and their functional properties are discussed. Mobilization and endothelial progenitor cell-mediated neovascularization is critically regulated. Stimulatory (eg, statins and exercise) or inhibitory factors (risk factors for coronary artery disease) modulate progenitor cell levels and, thereby, affect the vascular repair capacity. Moreover, recruitment and incorporation of endothelial progenitor cells requires a coordinated sequence of multistep adhesive and signaling events including adhesion and migration (eg, by integrins), chemoattraction (eg, by SDF-1/CXCR4), and finally the differentiation to endothelial cells. This review summarizes the mechanisms regulating endothelial progenitor cell-mediated neovascularization and reendothelialization.
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              Adult cardiac stem cells are multipotent and support myocardial regeneration.

              Antonio P Beltrami, Laura Barlucchi, Daniele Torella … (2003)
              The notion of the adult heart as terminally differentiated organ without self-renewal potential has been undermined by the existence of a subpopulation of replicating myocytes in normal and pathological states. The origin and significance of these cells has remained obscure for lack of a proper biological context. We report the existence of Lin(-) c-kit(POS) cells with the properties of cardiac stem cells. They are self-renewing, clonogenic, and multipotent, giving rise to myocytes, smooth muscle, and endothelial cells. When injected into an ischemic heart, these cells or their clonal progeny reconstitute well-differentiated myocardium, formed by blood-carrying new vessels and myocytes with the characteristics of young cells, encompassing approximately 70% of the ventricle. Thus, the adult heart, like the brain, is mainly composed of terminally differentiated cells, but is not a terminally differentiated organ because it contains stem cells supporting its regeneration. The existence of these cells opens new opportunities for myocardial repair.
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                Author and article information

                Contributors
                Zhongjie Sun
                Journal
                Journal ID (nlm-ta): Genes Dis
                Journal ID (iso-abbrev): Genes Dis
                Title: Genes & Diseases
                Publisher: Chongqing Medical University
                ISSN (Print): 2352-4820
                ISSN (Electronic): 2352-3042
                Publication date PMC-release: 28 July 2014
                Publication date Collection: September 2014
                Publication date (Electronic): 28 July 2014
                Volume: 1
                Issue: 1
                Pages: 113-119
                Affiliations
                [a ]Yale University, New Haven, CT 06520, USA
                [b ]Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
                Author notes
                [∗ ] Corresponding author. Research Committee, The Robert & Mary Cade Laboratory, BMSB 662A, Box 26901, Department of Physiology, BMSB 662A, College of Medicine, University of Oklahoma Health Sciences Center (OUHSC), 940 S.L. Young Blvd., Oklahoma City, OK 73126-0901, USA. Tel.: +1 405 271 2226x56237; fax. +1 405 271 3181. Zhongjie-sun@ 123456ouhsc.edu
                Article
                Publisher ID: S2352-3042(14)00008-7
                DOI: 10.1016/j.gendis.2014.07.003
                PMC ID: 4307803
                PubMed ID: 25642448
                SO-VID: b00681ff-2a47-492b-8666-b7d17f270906
                Copyright © Copyright © 2014, Chongqing Medical University. Production and hosting by Elsevier B.V. All rights reserved.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                Date received : 11 July 2014
                Date accepted : 17 July 2014
                Categories
                Subject: Article

                Keywords: adult stem cells,cardiovascular disease,embryonic stem cells,endothelial progenitor cells,hematopoietic stem cells,mesenchymal stem cells,myocardial repair,pluripotent potent stem cells
                Data availability:
                Keywords: adult stem cells, cardiovascular disease, embryonic stem cells, endothelial progenitor cells, hematopoietic stem cells, mesenchymal stem cells, myocardial repair, pluripotent potent stem cells

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