Unlocking the Pragmatic Potential of Regenerative Therapies in Heart Failure with Next-Generation Treatments

Abstract

Patients with chronic heart failure (HF) have a poor prognosis due to irreversible impairment of left ventricular function, with 5-year survival rates <60%. Despite advances in conventional medicines for HF, prognosis remains poor, and there is a need to improve treatment further. Cell-based therapies to restore the myocardium offer a pragmatic approach that provides hope for the treatment of HF. Although first-generation cell-based therapies using multipotent cells (bone marrow-derived mononuclear cells, mesenchymal stem cells, adipose-derived regenerative cells, and c-kit-positive cardiac cells) demonstrated safety in preclinical models of HF, poor engraftment rates, and a limited ability to form mature cardiomyocytes (CMs) and to couple electrically with existing CMs, meant that improvements in cardiac function in double-blind clinical trials were limited and largely attributable to paracrine effects. The next generation of stem cell therapies uses CMs derived from human embryonic stem cells or, increasingly, from human-induced pluripotent stem cells (hiPSCs). These cell therapies have shown the ability to engraft more successfully and improve electromechanical function of the heart in preclinical studies, including in non-human primates. Advances in cell culture and delivery techniques promise to further improve the engraftment and integration of hiPSC-derived CMs (hiPSC-CMs), while the use of metabolic selection to eliminate undifferentiated cells will help minimize the risk of teratomas. Clinical trials of allogeneic hiPSC-CMs in HF are now ongoing, providing hope for vast numbers of patients with few other options available.

In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging

“…In recent years, transplantation of cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) has shown promise in replenishing lost cardiomyocytes and, a few clinical trials are ongoing ( 3 , 4 ). However, no clinical method has been established to confirm the engraftment and viability of transplanted human iPSC-derived cardiomyocytes (iPSC-CMs).…”

Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells

“…If the implantation process does not achieve this, most of the cells were not retained in myocardium. Since the blade tip of a normal injection needle would cause bleeding that interferes with the process of transplantation, recent research has found that an injection needle with a cone-shaped blind end without a blade at the tip would reduce the bleeding interference that otherwise caused by conservative blade [36]. It has six holes on the side for injecting CM Spheroids into heart tissue.…”

Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells

“…If the implantation process does not achieve this, most of the cells are not retained in the myocardium. Furthermore, since the blade tip of a normal injection needle would cause bleeding that interferes with the process of transplantation, recent research has found that an injection needle with a cone-shaped blind end without a blade at the tip would reduce the bleeding interference that is otherwise caused by a conservative blade [ 45 ]. It has six holes on the side for injecting CM Spheroids into heart tissue.…”