Development of a Human Cardiac Tissue-Based Angiogenesis Model

Abstract

Previous angiogenesis models use animal tissues such as the chicken chorioallantoic membrane (CAM) or the rabbit cornea. These models may not accurately reflect the mechanisms responsible for human angiogenesis. We hypothesized that fragments of human myocardial tissue would develop an angiogenic response from the cut edges of vessels contained within the tissue. To test these hypotheses, we obtained human atrial appendage tissue at the time of cardiac bypass. Fragments of atrial tissue were then incorporated into fibrin thrombin clots. Tissue fragments were observed, and the percent of wells that developed neovessel invasion into the clot was calculated (%I). The subsequent growth of cardiac-derived microvessels was rated and scored over time (Angiogenic Index). There were 20 human atrial appendages plated (n = 24 to 60 wells/specimen) and evaluated in this model. Out of the 20, 16 (80%) atrial appendages developed an angiogenic response in the majority (>50%) of wells plated. Neovessel growth was progressive over 14 to 16 days in culture in all specimens tested. The mean angiogenic index of all specimens was 8.59 +/- 0.91. This human cardiac tissue-based assay might be useful to screen compounds designed for use in human trials or provide highly vascularized cardiac tissue for autotransplantation. Additionally, the assay provides the foundation to study an individual patent's cardiac tissue and its response to angiogenesis stimulators or inhibitors. This may allow the development of patient-specific therapies designed to enhance revascularization or repair of injured cardiac muscle.