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      Regenerating the Cardiovascular System Through Cell Reprogramming; Current Approaches and a Look Into the Future

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          Abstract

          Cardiovascular disease (CVD), despite the advances of the medical field, remains one of the leading causes of mortality worldwide. Discovering novel treatments based on cell therapy or drugs is critical, and induced pluripotent stem cells (iPS Cells) technology has made it possible to design extensive disease-specific in vitro models. Elucidating the differentiation process challenged our previous knowledge of cell plasticity and capabilities and allows the concept of cell reprogramming technology to be established, which has inspired the creation of both in vitro and in vivo techniques. Patient-specific cell lines provide the opportunity of studying their pathophysiology in vitro, which can lead to novel drug development. At the same time, in vivo models have been designed where in situ transdifferentiation of cell populations into cardiomyocytes or endothelial cells (ECs) give hope toward effective cell therapies. Unfortunately, the efficiency as well as the concerns about the safety of all these methods make it exceedingly difficult to pass to the clinical trial phase. It is our opinion that creating an ex vivo model out of patient-specific cells will be one of the most important goals in the future to help surpass all these hindrances. Thus, in this review we aim to present the current state of research in reprogramming toward the cardiovascular system's regeneration, and showcase how the development and study of a multicellular 3D ex vivo model will improve our fighting chances.

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          Most cited references98

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          Angiogenesis in life, disease and medicine.

          The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
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            Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.

            G Martin (1981)
            This report describes the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice. The pluripotency of these embryonic stem cells was demonstrated conclusively by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types. Such embryonic stem cells were isolated from inner cell masses of late blastocysts cultured in medium conditioned by an established teratocarcinoma stem cell line. This suggests that such conditioned medium might contain a growth factor that stimulates the proliferation or inhibits the differentiation of normal pluripotent embryonic cells, or both. This method of obtaining embryonic stem cells makes feasible the isolation of pluripotent cells lines from various types of noninbred embryo, including those carrying mutant genes. The availability of such cell lines should made possible new approaches to the study of early mammalian development.
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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                20 August 2018
                2018
                : 5
                : 109
                Affiliations
                The Wellcome-Wolfson Building, Centre for Experimental Medicine, Queen's University Belfast , Belfast, United Kingdom
                Author notes

                Edited by: Gabor Foldes, Imperial College London, United Kingdom

                Reviewed by: Koralia Paschalaki, Imperial College London, United Kingdom; Elisa Avolio, University of Bristol, United Kingdom

                *Correspondence: Andriana Margariti a.margariti@ 123456qub.ac.uk

                This article was submitted to Cardiovascular Biologics and Regenerative Medicine, a section of the journal Frontiers in Cardiovascular Medicine

                Article
                10.3389/fcvm.2018.00109
                6109758
                3f6e0c26-0227-42e0-9424-30a928d487e9
                Copyright © 2018 Tsifaki, Kelaini, Caines, Yang and Margariti.

                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
                : 04 June 2018
                : 24 July 2018
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 138, Pages: 12, Words: 9598
                Categories
                Cardiovascular Medicine
                Mini Review

                reprogramming,vascular cells,regeneration,cardiovascular system,induced pluripotent stem cells (ips cells)

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