Cardiac cell therapy: Lessons from clinical trials

Cardiac cell therapy has now been in clinical use since 10 years. Both autologous skeletal myoblasts and bone marrow-derived different cell subsets (mononuclear cells, hematopoietic progenitors, mesenchymal stem cells) have been investigated in different settings (acute myocardial infarction, refractory angina and chronic heart failure). Despite the huge variability in cell processing techniques, dosing, timing of delivery and route for cell transfer, some lessons can yet be drawn, primarily from randomized controlled trials and summarized as follows: Techniques used for cell preparation are reasonably well controlled although better standardization and improvement in scale-up procedures remain necessary; cell therapy is overall safe, with the caveat of ventricular arrhythmias which still require careful scrutinization; the cell type needs to be tailored to the primary clinical indication, whereas the paracrine effects of bone marrow cells may be therapeutically efficacious for limitation of remodelling or relief of angina, only cells endowed with a true cardiomyogenic differentiation potential are likely to effect regeneration of chronic scars; autologous cells are primarily limited by their variable and unpredictable functionality, thereby calling attention to banked, consistent and readily available allogeneic cell products provided the immunological issues inherent in their use can be satisfactorily addressed; regardless of the cell type, a meaningful and sustained therapeutic benefit is unlikely to occur until cell transfer and survival techniques are improved to allow greater engraftment rates; and trial end points probably need to be reassessed to focus on mechanistic issues or hard end points depending on whether new or already extensively used cells are investigated. Hopefully, these lessons may serve as a building block whose incorporation in the design of second-generation trials will help making them more clinically successful. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".