Enhancing the Outcome of Cell Therapy for Cardiac Repair

Abstract

Cell therapy has emerged as a promising option to treat myocardial infarction or heart failure; more than 1500 patients with cardiovascular diseases are treated with adult progenitor cells worldwide. The treatment of acute and chronic myocardial infarction with adult bone marrow-derived cells provided a modest benefit in most but not all studies. A number of plausible reasons have been discussed to explain the modest effects, sending researchers back to the bench to elucidate strategies to overcome the limitations of cell therapy and to develop more efficient approaches. Such strategies include the use of other sources to isolate adult progenitor cells (eg, adipose or cardiac tissue) or the generation of pluripotent cells by the reprogramming of somatic cell types. Successful cardiac cell therapy in clinical practice also depends on the efficient delivery and the appropriate integration and alignment of injected or infused cells. The pretreatment of cells with activators to augment cell homing and survival or the improvement of cell delivery tools may provide an opportunity to increase the number of active cells in ischemic or diseased tissues, thereby increasing their therapeutic potential. Finally, the identification of molecules guiding cardiac differentiation provides novel tools to enforce the formation of new functionally active cardiomyocytes to augment cardiac regeneration in its pure sense. This section provides a short overview of the different cell types that have been or are currently being tested for the treatment of patients with acute myocardial infarction or chronic heart failure (Figure 1). Most of the clinical studies performed so far have used bone marrow-derived mononuclear cells (BMCs) for treating patients with acute or chronic infarcts (for review, see elsewhere1). Overall, a modest but significant benefit was seen in meta-analyses of all published studies.2,3 Particularly in the acute setting, the infusion of BMCs via balloon catheters into …