Cell Therapy for Cardiac Regeneration after Myocardial Infarct: Which Cell is the Best?

Federico      Mosna; Francesco      Annunziato; Giovanni      Pizzolo; Mauro      Krampera

Abstract

In the last decade several attempts have been made to achieve the goal of cardiac regeneration after myocardial infarction. To date, two cell types have completed phase-III clinical trials: Skeletal Myoblasts and Bone-Marrow Mononuclear Cells (BM-MNCs). In the first case, all benefits have been limited by an increased risk of arrhythmia. In the case of BM-cells, most studies showed a significant, although limited, advantage in the cell-treated group. This may be due to the choice of the wrong BM cell type: other candidates would be e.g. CD34+ HSCs, or non-hematopoietic Mesenchymal Stem Cells. After positive results from the experimental studies, phase I/II clinical trials are currently on-going for both.

Ideally, the best cell to use to regenerate the heart would be a precursor of all cardiac lineages; until the isolation and expansion of Cardiac Stem Cells (CSCs), such a cell was thought to exist only during embryogenesis. Using CSCs researchers managed to generate electrically-coupled contractile tissue within the infarct of animal models. Still, some doubts persist over the possibility to translate such results in real-life patients.

Another approach, therefore, involves the use of induced Pluripotent Stem Cells (iPS) obtained from fibroblasts after genetic reprogramming. This new type of cell would combine the pluripotency of embryonal stem cells with the advantages of an autologous use. Nevertheless, iPS cells form teratomas, and their effective differentiation in vivo is largely unknown.

This review will critically compare the data from the Literature concerning cell therapy after myocardial infarction. Can we name the best cell?

Keywords: Adult stem cells, cardiac regeneration, cell therapy, bone marrow, mesenchymal stem cells, cardiac stem cells, induced pluripotent stem cells, acute myocardial infarction