Introducción

The overall patient mortality from coronary artery disease (CAD) has declined because of several factors including improvements in pharmacologic therapy and revascularization techniques1. However, cardiovascular disease still remains the leading cause of death in the world2. The life-saving advances in management of acute and chronic CAD have been associated with an increased prevalence of patients with heart failure (HF), with an estimated 250,000–350,000 patients who may be candidates for more advanced therapies3. Additionally, HF, like all cardiovascular diseases, is highly age dependent, and the prevalence will potentially double by 2030 with the advancing age of the US and world populations4.

Standard therapeutic options for patients who develop advanced HF are limited and include heart transplantation or the use of ventricular assist devices (VADs), both of which are limited by cost, availability, and complications5. This results in a large HF patient population with progressive symptoms and limited treatment options6. Firstgeneration autologous cell therapies (derived from bone marrow, blood, or adipose tissue) for advanced HF have shown promise but have had limited and nondurable results due to lack of potency, low cell number, low retention, or limited biological function7–10. The goal of cell therapy, which utilizes the body’s native repair mechanisms, is to reverse or restore the function of organs, tissues, and blood vessels. The newest generation of cell therapies will involve the use of autologous or allogeneic cultured and expanded cell products, ideally with defined potency, doses, low immunogenicity, and potential reproducibility. Umbilical cord tissue-derived cells, such as umbilical cord subepithelial cells (UCSECs), have some of these qualities, as they have been shown to have low to no immunogenicity in in vitro, preclinical, and early clinical studies11–19.

In addition to having better cell therapy options for HF patients, safer, more cost-effective, and reproducible 1714 Tuma ET AL. delivery techniques are required. There are robust preclinical models of retrograde delivery of cells demonstrating safety and efficacy20. Our group has previously demonstrated the safety and reproducibility of retrograde delivery of first-generation cell types in both chronic angina and HF patients21,22. The goal of this study was to evaluate the safety and feasibility of retrograde delivery of a large dose range of xeno-free allogeneic UCSECs in patients with HF (RESCUE-HF).