Strategies in cardiac tissue engineering Richard Tee,* Zerina Lokmic,*† Wayne A. Morrison*†‡ and Rodney J. Dilley*‡§ *O’Brien Institute, Fitzroy †The Department of Surgery, University of Melbourne ‡The Department of Plastic Surgery, St Vincent’s Hospital §Australian Tissue Engineering Centre, Melbourne, Victoria, Australia Key words heart transplantation, myocardium, review, stem cells, tissue engineering. Abbreviations AD-MSCs, Adipose-derived mesenchymal stem cells; AVL, Arteriovenous loop; BM-MSCs, Bone marrow-derived mesenchymal stem cells; CTE, Cardiac Tissue Engineering; CMs, Cardiomyocytes; EC, Endothelial cells; ESCs, Embryonic stem cells; EHT, Engineered heart tissue; ECM, Extracellular matrix; iPS, Induced pluripotent stem; PC, Pericytes; PDGF-B, Platelet-derived growth factor-B; PGA, Polyglycolic acid; PLA, Poly(lactic acid); PU, Polyurethrane. Correspondence Dr Richard Tee, O’Brien Institute, 42 Fitzroy Street, Fitzroy, Vic. 3065, Australia. Email: richard.tee@svhm.org.au R. Tee MB BS; Z. Lokmic PhD; W. A. Morrison MD, FRACS; R. J. Dilley PhD. The corresponding author was a recipient of a Reg Worchester Foundation of Surgery Fellowship. Accepted for publication 21 April 2010. doi: 10.1111/j.1445-2197.2010.05435.x Abstract In heart failure, post-myocardial infarction and some congenital cardiac anomalies, organ transplantation is the only effective cure. Shortage of organ donors and com- plications of orthotopic heart transplant remain major challenges to the modern field of transplantation. Tissue engineering using cell-based strategies presents itself as a new way of generating functional myocardium. Engineering functional myocardium de novo requires an abundant source of cells that can form cardiomyocytes. These cells may be used with biocompatible scaffold materials to generate a contractile myocar- dium. Lastly, to sustain the high metabolism of the construct, a functional vasculature needs to be developed with the forming cardiac tissue. This review provides an update on the progress of stem cell research in the context of cardiac tissue development, types of biomaterials used in cardiac tissue engineering (CTE) and currently employed strategies for vascularization in CTE. In addition, a brief overview of strategies utilized in CTE is provided. Introduction In end-stage heart failure and many congenital cardiac anomalies, the requirement for heart transplantation is inevitable. While various surgical procedures and pharmacological therapies can prolong the life span, neither provides a cure. Heart transplantation results in an effective treatment; however, there is a shortage of donor organs. In addition, organ rejection and/or failure, life-long requirement for immunosuppression therapy and complications of that therapy further threaten the long-term success of heart transplants. 1 An alter- native cardiac tissue source is required to address a growing need. This alternative source of cardiac tissue is most likely to arise from the collective efforts of the tissue engineering field, where through a multi-disciplinary approach to in vivo and in vitro tissue development, new organs may be generated for transplantation and tissues for reconstruction, referred to as organoids or constructs. For the purpose of this review, a term ‘cardiac construct’ will be used to describe tissue-engineered myocardium products. The National Science Foundation (USA) defined tissue engineering as, ‘an inter- disciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain or improve tissue function’. 2 Over the last two decades, early successes in cartilage, skin and bone tissue engineer- ing has received widespread media attention, none more than the ‘human ear on the mouse back’ model from Cao et al. 3 However, this attention generated high expectation of the young field, whose CLINICAL REVIEW ANZJSurg.com © 2010 The Authors ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons ANZ J Surg •• (2010) ••–••