Current outlook of cardiac stem cell therapy towards a clinical application
- University Medical Center Utrecht, Division Cardiology & Pulmonology, Interventional Cardiology Department, Utrecht, The Netherlands
- Correspondence to Dr Henricus J Duckers, University Medical Center Utrecht, Division Cardiology & Pulmonology, Interventional Cardiology Department, Room E04-201 Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;
Cardiovascular diseases are the major cause of death worldwide and currently affect 36.3% of the US population.w1 The majority of this population comprises patients with acute myocardial infarction (AMI) and chronic ischaemic heart failure. Despite the considerable contribution of percutaneous coronary revascularisation and coronary artery bypass grafting (CABG) in coronary artery disease (CAD) patients, the long term benefits remain unsatisfactory. Moreover, heart transplantation, as a last resort, is available for a very limited patient population.
Cell transplantation emerged initially as a potential therapy to treat heart failure. Cardiomyocytes are generally considered to be post-mitotic, and do not regenerate upon loss or damage. However, recently Bergmann and co-workers were able to demonstrate that 50% of adult cardiomyocytes are exchanged during a normal lifespan,1 which has propelled investigations into the potential use of cardiovascular regenerative therapy. Moreover, recent improvements in preparation techniques of stem cells, the creation of stable stem cell lines (master cell banks), as well as the isolation of omnipotent embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells, underscore the potential of stem cell therapy as a viable new avenue in the treatment regimen of cardiac patients.
The majority of preclinical studies and clinical trials to date have evaluated the efficacy of cell therapy mainly in AMI. Cell therapy in the acute phase of a myocardial infarction (MI) is geared towards prevention of cardiomyocyte apoptosis, promotion of local neoangiogenesis, improving myocardial perfusion, and reduction of the local inflammatory response. These will all result in sustained contractile function and a reduction of adverse post-AMI cardiac remodelling, ultimately decreasing major adverse cardiac events and progression into overt chronic heart failure. Numerous preclinical studies and meta-analyses of randomised controlled clinical trials suggest that stem cell therapy by either intravascular or intramyocardial injection in ischaemic heart disease is safe, feasible …