The Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis Pilot Study (The POSEIDON-Pilot Study)

The technique of transplanting progenitor cells into a region of damaged myocardium, termed
cellular cardiomyoplasty, is a potentially new therapeutic modality designed to replace or
repair necrotic, scarred, or dysfunctional myocardium. Ideally, graft cells should be
readily available, easy to culture to ensure adequate quantities for transplantation, and
able to survive in host myocardium; often a hostile environment of limited blood supply and
immunorejection. Whether effective cellular regenerative strategies require that
administered cells differentiate into adult cardiomyocytes and couple electromechanically
with the surrounding myocardium is increasingly controversial, and recent evidence suggests
that this may not be required for effective cardiac repair. Most importantly,
transplantation of graft cells should improve cardiac function and prevent adverse
ventricular remodeling. To date, a number of candidate cells have been transplanted in
experimental models, including fetal and neonatal cardiomyocytes, embryonic stem
cell-derived myocytes, tissue engineered contractile grafts, skeletal myoblasts, several
cell types derived from adult bone marrow, and cardiac precursors residing within the heart
itself. There has been substantial clinical development in the use of whole bone marrow and
skeletal myoblast preparations in studies enrolling both post-infarction patients, and
patients with chronic ischemic left ventricular dysfunction and heart failure. The effects
of bone-marrow derived mesenchymal stem cells (MSCs) have also been studied clinically.

Currently, bone marrow or bone marrow-derived cells represent highly promising modality for
cardiac repair. The totality of evidence from trials investigating autologous whole bone
marrow infusions into patients following myocardial infarction supports the safety of this
approach. In terms of efficacy, increases in ejection fraction are reported in the majority
of the trials.

Chronic ischemic left ventricular dysfunction resulting from heart disease is a common and
problematic condition; definitive therapy in the form of heart transplantation is available
to only a tiny minority of eligible patients. Cellular cardiomyoplasty for chronic heart
failure has been studied less than for acute MI, but represents a potentially important
alternative for this disease.