Phases I-III Clinical Trials Using Adult Stem Cells

Abstract

First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomized clinical trials and their limitations, discuss the key points in the design of future trials, and depict new directions of research in this fascinating field.

Figure 1

Autologous adipose-derived mesenchymal stem cells during mitosis (a) and growing in colonies in the 6th day of culture (magnification ×10, (b)). These cells were expanded from the adipose tissue stroma-vascular fraction under good manufacturing practice (GMP) conditions in our Cell Production Unit (Hospital Gregorio Marañón, Madrid).

Figure 2

Electromechanical mapping of the left ventricle with the NOGA XP System (BDS, Cordis Corporation, Johnson and Johnson) from a patient enrolled in the PRECISE trial in our centre. Myocardial areas with low contractility and impaired endocardial voltage are identified as viable and targeted for cell injection (brown dots).

Figure 3

Proposed mechanisms of stem cell function after homing into the damaged heart. Note that differentiation processes and paracrine effects activate a cascade of events that interact actively to create new blood vessels and cardiomyocytes, with the final objective of functional cardiac repair. CSCs: cardiac stem cells.