Cardiac Progenitor Cell Therapy for Heart Repair — Regenerative Therapies

Heart-derived progenitor cells and cardiosphere-derived cells (CDCs) for myocardial regeneration after infarction and in cardiomyopathy.

Overview

Cardiac Progenitor Cell (CPC) therapy encompasses several approaches to regenerate damaged myocardium, primarily using cardiosphere-derived cells (CDCs) and c-kit+ cardiac progenitor cells. CDCs, pioneered by Eduardo Marban at Cedars-Sinai, are harvested from endomyocardial biopsy, grown as self-assembling cardiospheres, and expanded as CDCs. The CADUCEUS trial (2012) demonstrated that intracoronary CDC infusion reduced scar size by 42% at 12 months post-MI. The ALLSTAR trial, a larger Phase 2 study, showed safety but did not meet its primary endpoint of scar reduction. The c-kit+ cardiac stem cell field was severely damaged by the HARVARD/Piero Anversa scandal - 31 papers retracted for fabrication, and Brigham and Women's Hospital paid $10 million to settle.

Indications

  • Post-myocardial infarction (scar reduction and remodeling)
  • Ischemic cardiomyopathy with reduced ejection fraction
  • Duchenne muscular dystrophy cardiomyopathy (HOPE-Duchenne trial)
  • Heart failure with reduced ejection fraction (HFrEF)
  • Non-ischemic dilated cardiomyopathy (investigational)

Mechanism of Action

Endomyocardial biopsy tissue explanted and cultured. Cardiac progenitors migrate out and form self-assembling cardiospheres - 3D clusters containing c-kit+ cells, MSC-like cells, and cardiac progenitors

Dosing

CompoundDoseFrequencyNotes
Cardiosphere-Derived Cells (CDCs)25 million CDCsSingle infusion 1.5-3 months post-MIIntracoronary infusion via balloon catheter (CADUCEUS trial)
CAP-1002 (Allogeneic CDCs)150 million allogeneic CDCsSingle infusion, may repeat quarterlyCAP-1002 for DMD cardiomyopathy (HOPE-Duchenne)

Evidence Grade

GRADE C

Safety & Contraindications

  • Intracoronary delivery requires cardiac catheterization
  • Risk of coronary microembolization and slow flow/no-reflow phenomenon
  • Endomyocardial biopsy for autologous harvest carries perforation risk
  • c-kit+ cardiac stem cell field tainted by Anversa data fabrication scandal
  • Allogeneic CDCs may trigger immune response
  • Arrhythmia risk from cell transplantation into scarred myocardium
  • ALLSTAR Phase 2 trial failed primary endpoint - efficacy uncertain
  • Long-term durability of scar reduction benefits unclear
  • Limited to specialized cardiac centers with interventional capabilities