Cell therapy trials for heart regeneration — lessons learned and future directions

Abstract

The effects of cell therapy on heart regeneration in patients with chronic cardiomyopathy have been assessed in several clinical trials. These trials can be categorized as those using noncardiac stem cells, including mesenchymal stem cells, and those using cardiac-committed cells, including KIT cardiac stem cells, cardiosphere-derived cells, and cardiovascular progenitor cells derived from embryonic stem cells. Although the safety of cell therapies has been consistently reported, their efficacy remains more elusive. Nevertheless, several lessons have been learned that provide useful clues for future studies. This Review summarizes the main outcomes of these studies and draws some perspectives for future cell-based regenerative trials, which are largely based on the primary therapeutic target: remuscularization of chronic myocardial scars by exogenous cells or predominant use of these cells to activate host-associated repair pathways though paracrine signalling. In the first case, the study design should entail delivery of large numbers of cardiac-committed cells, supply of supportive noncardiac cells, and promotion of cell survival and appropriate coupling with endogenous cardiomyocytes. If the primary objective is to harness endogenous repair pathways, then the flexibility of cell type is greater. As the premise is that the transplanted cells need to engraft only transiently, the priority is to optimize their early retention and possibly to switch towards the sole administration of their secretome.

Efficient Cardiac Differentiation of Human Amniotic Fluid-Derived Stem Cells into Induced Pluripotent Stem Cells and Their Potential Immune Privilege

“…However, there are several hurdles that have to be overcome prior to the clinical application of cell therapy for cardiac regeneration. One of these major obstacles is the post-transplant rejection of allogeneic cell transplantation [22][23][24]. Owing to the mismatch of HLA antigens, transplanted cells can be rejected.…”

Wearable and Implantable Devices for Cardiovascular Healthcare: from Monitoring to Therapy Based on Flexible and Stretchable Electronics

“…Hence, cell‐based therapies have gained attention for their capability to treat damaged cardiac tissue . Cell therapies for ischemic heart diseases and heart failure have been performed in clinical trials . In most of these clinical trials, cells were directly injected into an infarcted area or the corresponding coronary artery ( Figure a) .…”

Turning regenerative technologies into treatment to repair myocardial injuries

“…MSCs exhibit limited cardiomyogenic potential and are currently considered for the high secretory profile rather than as exogenous cells to replace lost heart cardiomyocytes . Excellent reviews that were recently published describe the most relevant pre‐clinical and clinical studies of cell‐based therapies …”