Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

Abstract

Heart failure (HF), a common sequela of cardiovascular diseases, remains a staggering clinical problem, associated with high rates of morbidity and mortality worldwide. Advances in pharmacological, interventional, and operative management have improved patient care, but these interventions are insufficient to halt the progression of HF, particularly the end-stage irreversible loss of functional cardiomyocytes. Innovative therapies that could prevent HF progression and improve the function of the failing heart are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many potential gene-and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell-and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies. The principles and mechanisms of action of gene and cell therapies for HF are discussed along with the limitations of current approaches. Finally, we highlight the emerging technologies that hold promise to revolutionize the biological therapies for cardiovascular diseases. STEM CELLS 2017;35:1131-1140 SIGNIFICANCE STATEMENTInnovative therapies that could treat heart failure and improve the function of failing hearts are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many gene-and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell-and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies that have entered the clinical arena.

Cardiac Stem Cells in the Postnatal Heart: Lessons from Development

“…Comprehensive surveys of these trials concluded an overall modest efficacy in improving cardiac function, indicating considerable variance and discrepancy with animal studies, while the long-term benefits remained uncertain [ 134 – 138 ]. For instance, of a dozen studies using injected bone marrow mononuclear cells, three noted an improved left ventricular ejection fraction, whereas other studies did not record differences in the patients' cardiac parameters, and the optimal timing of these injections after cardiac injury also remained unclear [ 135 ]. The much larger BAMI randomised controlled trial may be more conclusive on bone marrow mononuclear cells [ 134 ].…”

Expansion of Human Pluripotent Stem Cell-derived Early Cardiovascular Progenitor Cells by a Cocktail of Signaling Factors

“…In this regard, researchers propose the use of different cell sources, including those which have been isolated from both non-cardiac and cardiac origins 3 . Among these various cell sources, adult stem cells isolated from non-cardiac origins such as bone marrow-derived stem cells, could not efficiently differentiate into three major cardiac lineages and their regenerative benefits for cardiovascular diseases remain controversial 4 . However, the majority of these cells appear to be clinically safe and their positive impacts on heart performance are mostly attributed to paracrine effects.…”

CCN5/WISP2 and metabolic diseases

“…In fact, studies investigating the effect of MSC transplantation, or other stem cell-like cells, in patients with heart failure have shown that the retention and engraftment of transplanted MSCs in the myocardium is disproportional in size and duration to the functional benefits reported. These indirect effects have been attributed to both cell-cell contact and the production and release of positive endocrine factors (Chen et al 2017 ; Gnecchi et al 2008 ; Leiker et al 2008 ).…”