Stem Cells and Cardiac Repair

Discovery of tissue specific stem cells capable of forming cardiac cell types has revolutionized cardiac medicine. Not long ago, cardiac tissue regeneration was considered an impossible task. The last ten years however has seen an explosion of cell based therapeutic approaches stimulating cardiac regeneration and in the process augmenting function in the heart following injury. Encouraging preclinical results have paved the way for clinical applications of cell therapy and preliminary results obtained from various clinical trials indicate that stem cell transplantation increases cardiac function comparable to the existing interventions for treatment of heart diseases. These are promising outcomes that indicate that the cells have the ability to modulate cardiac repair programs leading to replacement of the lost tissue. Nevertheless, the search continues for the optimal cell type that can promote " true cardiac regeneration, " supplement the lost cardiomyocytes, and at the same time form the angiogenic support structure. One of the first stem cell types to be used for cardiac regeneration was derived from the mononuclear fraction of the bone marrow and the cells were designated as bone marrow mononuclear cells [1]. Ensuing years saw establishment of the finding that the bone marrow is host to a variety of distinct stem/progenitor cell populations possessing cardiogenic repair potential. The study by D. Orlic et al. in the early part of the last decade showed that transplantation of lin − /c-kit+ cells effectively transdifferentiates into cardiac lineages leading to enhanced cardiac function after infarction [2]. At the same time, a large body of evidence pointed towards a role for bone marrow derived mesenchymal stem cells (MSCs) in the repair of the damaged heart [3]. Nevertheless, the search for a heart resident stem cell population continued till A. P. Beltrami et al. showed that the adult heart contains a resident stem cell population capable of differentiating into all three cardiac lineages (myocytes, endothelial, and smooth muscle cells) [4]. In addition to these widely studied stem cell types, researchers have used other extra cardiac stem cell types such as adipose derived stem cells [5], cortical bone derived stem cells [6], and cord blood stem cells for cardiac repair. Despite the excitement, significant concerns persist around the ability of adoptively transferred cells to survive in the ischemic heart and some reports suggest as low as 1% of cells make it in the heart past the first few days of transplantation. Most of the salutary …