Cardiac tissue engineering and regeneration using cell-based therapy

Stem Cells and Cloning: Advances and Applications Dovepress open access to scientific and medical research Review Stem Cells and Cloning: Advances and Applications downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Cardiac tissue engineering and regeneration using cell-based therapy This article was published in the following Dove Press journal: Stem Cells and Cloning: Advances and Applications 14 May 2015 Number of times this article has been viewed Mohammad T Alrefai 1–3 Divya Murali 4 Arghya Paul 4 Khalid M Ridwan 1,2 John M Connell 1,2 Dominique Shum-Tim 1,2 Division of Cardiac Surgery, Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA 1 2 Correspondence: Dominique Shum-Tim The Royal Victoria Hospital, Suite S8.73.B, 687 Pines Avenue West, Montreal, QC H3A 1A1, Canada Tel +1 514 934 1934 ext 36873 Fax +1 514 843 1602 Email Introduction It is well known that cardiovascular disease is a main cause of morbidity and mortality worldwide.1 Traditional medical and surgical therapies have had success in the treatment of many cardiovascular diseases, such as coronary artery disease and valvular diseases, but have had limited success in the therapy of damaged myocardium. Acute ischemic myocardial damage and chronic myocardial failure have been challenging conditions for which to provide an adequate long-term prognosis, although a recent study by Beltrami et al,2 demonstrated the ability of cardiac cells (cardiomyocytes) to divide after the occurrence of myocardial infarction (MI), and reentering the human cell cycle, but that may not be enough to provide the needed quantity of cells to restore the damage; the common belief before that study was that myocytes are unable to divide depending on the interpretation of the scar formation after the infarction. This aspect widens our perspective of the management approach – from being dependent solely on medical, percutaneous coronary intervention (PCI) and a surgical approach, to include a new side for management that includes the application of stem cell therapy – as these conditions have so far exceeded the reach of traditional medicine. The use of stem cells and tissue engineering has been tested in the laboratories and clinical trials as a potential solution for future treatment. When engineering tissue for use as a cardiovascular therapy, there are three main points to consider: scaffolds, cell sources, and signaling factors. 81 submit your manuscript | www.dovepress.com Stem Cells and Cloning: Advances and Applications 2015:8 81–101 Dovepress © 2015 Alrefai et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/SCCAA.S54204 Powered by TCPDF (www.tcpdf.org) Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering Dovepress Alrefai et al Stem Cells and Cloning: Advances and Applications downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Scaffolds A “scaffold” is a substitute that provides a structural platform for a new cellular microenvironment that supports new tissue formation. It allows cell attachment, migration, differentiation, and organization that can aid in delivering soluble and bound biochemical factors.3 Cell sources The choice of cells to populate a scaffold depends on the purpose of the new tissue graft. The new cells will synthesize the bulk of the mass of a tissue matrix, and will form the integrating connections with existing native tissues. They also maintain tissue homeostasis in general and provide various metabolic supports to other tissues and organs. Terminally differentiated cells have been used with variable degrees of success and there are some limitations to their use in tissue engineering, but stem cells, and more recently adult stem cells, have become the major players in most new tissue replacement strategies.4 Their favorable properties are being harnessed to drive most new tissue engineering processes.5 Signaling factors Signaling factors can influence, and even direct, a new tissue’s phenotype. Their application has been learned from signals observed during native tissue formation and they have direct and indirect effects on cell metabolism, migration, and organization.3 Stem cell types used for cardiac repair Xenogeneic cells from nonhuman species have limitations in therapeutic strategies due to significant differences in antigens between species, potentially leading to graft rejection. Meanwhile, allogeneic cells from human donors are likely to have greater success after implantation. Allogeneic stem cells include umbilical cord-derived cells, fetal cardiomyocytes, and embryonic mesenchymal stem cells (EmSCs). These cells, however, are still potentially subjected to immune surveillance and rejection. To eliminate the potential for allogeneic rejection, autologous cells from the same individual have become a central focus of stem cell research. This category of cells includes skeletal myoblasts, adipose-derived stem cells (AdSCs), resident cardiac stem cells (RCSCs) and bone marrow-derived (BMD) stem cells, such as CD34+ cells, induced pluripotent stem cells (iPSCs), mesenchyma (...truncated)