Drugs, gene transfer, signaling factors: a bench to bedside approach to myocardial stem cell therapy

Abstract

In the past few years, the dogma that the heart is a terminally differentiated organ has been challenged. Evidence from preclinical investigations emerged that there are cells, even in the heart itself, that may be able to restore impaired cardiac function after myocardial infarction. Although the exact mechanisms by which the infarcted heart can be repaired by stem cells are not yet fully defined, there is a new optimism among cardiologists that this treatment will prove successful in addressing the cause of heart failure after myocardial infarction-myocyte loss. Despite the promising preliminary data of human myocardial stem cell trials, scientists have also focused on the possibility of enhancing the underlying mechanisms of stem cell repair to gain healthier myocardial tissue. Attempts to induce neo-angiogenesis by transfecting stem cells with signaling factors (such as VEGF), to raise the number of endothelial progenitor cells with medical treatments (such as statins), to transfect stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and to enhance the healing process after myocardial infarction with the use of various forms of stimulating factors (G-CSF, SCF, GM-CSF) have been made with notable results. In this article, we summarize the evidence from preclinical and clinical myocardial stem cell studies that have addressed the possibility of enhancing the regenerative capacity of cells used after myocardial infarction.

Intra-myocardial delivery of mesenchymal stem cells ameliorates left ventricular and cardiomyocyte contractile dysfunction following myocardial infarction

“…Consistent with our current experimental findings, several alternate avenues have been recommended to improve the survival rate and differentiation of stem cell to combat with the myocyte loss following MI. In particular, facilitated angiogenesis through signaling molecules (e.g., VEGF), increased endothelial progenitor cell number using medical treatments (such as statins), transfection of stem cells with heat shock protein 70 (as a cardioprotective agent against ischemia) and enhanced stem cell survival with various forms of stimulating factors (G-CSF, SCF, GM-CSF) have all been suggested to produce favorable outcomes (Vertesaljai et al 2008). …”

Targeting VEGF‐encapsulated immunoliposomes to MI heart improves vascularity and cardiac function

“…Recently, there has been much excitement and interest in developing regenerative strategies for curing heart disease using cell-based therapies. However, stemcell therapies have only resulted in modest improve-ments, if any, in cardiac function (1)(2)(3), and in some cases, these modest improvements may be a result of angiogenic cytokines released from transplanted stem cells, and not the division, differentiation, and incorporation of new stem cells into the existing myocardium (4 -6). The lack of a supporting microenvironment, and especially a microvascular framework, that is essential for stem-cell survival, engraftment, and proliferation, may be the key to unlocking the full potential of stem-cell therapies (7).…”

Effectiveness of Stem Cell Therapies in Improving Clinical Outcomes in Patients With Heart Failure

“…Evidence has emerged that suggests the possibility of regeneration of myocardial tissue using cardiac stem cells, based upon which numerous clinical trials are probing the use of stem cells from multiple origins as a therapeutic alternative in HF [5]. Available cell types that have the potential to replace lost myocardium include mesenchymal stem cells (MSCs), bone-marrow-derived cells (BMCs), embryonic stem cells (ESCs), cardiac progenitor cells (CPCs), skeletal myoblasts, and hematopoietic stem cells (HSCs) [6,7,8]. Multiple studies conducted in the last decade address the use of stem cells in patients of HF due to variable etiologies.…”