The Marbán Laboratory focuses on two disease themes. The first builds on the long-standing interest of Eduardo Marbán, MD, PhD, in the molecular basis of excitability to create novel, biologically based treatments for cardiac arrhythmias.
The Marbán Lab was the first to create a de novo biological pacemaker, work that is now proceeding toward first-in-human clinical testing. The laboratory is also developing extracellular vesicles as therapeutic agents for refractory ventricular tachycardia.
The second broad category of the Marbán Laboratory's research is in stem cells and regenerative medicine, which the team has pursued for 15 years. The Marbán Lab was the first to isolate and characterize cardiosphere-derived cells (CDCs), which are now in advanced clinical trials. The first manuscripts defined the engraftment, differentiation and functional benefit of CDCs in murine and porcine models of myocardial infarction. At Cedars-Sinai, the work has gone from proof-of-concept through completion of the first-in-human CADUCEUS clinical trial, which was a randomized clinical study funded by the National Institutes of Health. Autologous CDCs proved to be safe and effective in decreasing infarct size and improving regional function in post-MI patients with ventricular dysfunction.
Notably, the amount of living heart muscle increased (by about 22 grams at one year) in CDC-treated patients, but not in controls. This was the first demonstration in humans of therapeutic regeneration — the intentional regrowth of living tissue in an organ previously thought to be irreversibly damaged.
In other studies, the laboratory has shown that the mechanism of benefit is largely indirect, mediated by extracellular vesicles (exosomes). These insights form the basis of the ongoing clinical trials of allogenic CDCs — ALLSTAR (the ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration trial for moderate heart failure after myocardial infarction), HOPE (the Halt cardiomyOPathy progrEssion in Duchenne trial for Duchenne muscular dystrophy), Regress-HFpEF (Regression-Heart Failure with Preserved Ejection Fraction trial for heart failure with preserved ejection fraction) and ALPHA (ALlogeneic CDCs for Pulmonary Hypertension therapy). Work in the lab spans from mechanistic discovery science through advanced clinical trial design and analysis, a continuum to which trainees are rigorously exposed.
The Marbán Laboratory is affiliated with the Smidt Heart Institute, Department of Medicine and Barbra Streisand Women's Heart Center.