Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 403

The adult heart contains cardiac stem cells (CSCs) that express the unique surface receptor tyrosine kinase c-kit as well as other markers, such as Sca-1, and Isl-1. These cells are self-renewing, clonogenic, and multipotent, which allows them to differentiate into myocytes, vascular smooth muscle, and endothelial cells. CSCs are harvested via a minimally invasive biopsy or during cardiac surgery, isolated from others cells by markers, expanded in vitro, and can be frozen for subsequent use.

The first clinical trial to publish results on CSC treatment in heart disease was the SCIPIO Phase 1 trial, in which CSCs were harvested from right atrial appendages during coronary artery bypass graft (CABG) and eventually readministered via intracoronary injection. After one year, LVEF increased by 12.3 percent and post-AMI size decreased by 30 percent.

Another SCIPIO Phase I trial at the University of Louisville that analyzed results through cardiac magnetic resonance (CMR) found that at one year LVEF increased by 41.2 percent, global and regional LV function improved, post-AMI size decreased by 30 percent, and viable tissue increased.

Cardiosphere-derived SCs (CDCs) are clusters of core c-kit-positive SCs, differentiating cells, and outer MSCs that form from myocardial tissue under appropriate culture conditions. Studies importantly demonstrate that CDCs express connexin-43 and form gap junctions, which allows electrical coupling.

The 2012 CADUCEUS trial at Cedars-Sinai Heart Institute found via CMR that autolo-gous endomyocardial-CDCs 1.5 to three months post-AMI resulted in reduction of post-AMI size and an increase in both viable cardiac mass and regional contractility. Although this trial did not demonstrate significant changes in LVEF, recent studies suggest the importance of SC therapies would be missed if EF were the sole endpoint, as EF is dependent upon non-cardiac factors, such as the neurohormonal state.

Measures of LV remodeling, such as decrease in chamber volume, sphericity index, and reduction of post-AMI size prove more clinically meaningful to elucidate SC treatment efficacy.