Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self.

BACKGROUND: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. METHODS: We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. RESULTS: In addition to macrophages, we found a high proportion of αß T cells in the coronary plaques. Most of these T cells lack high expression of CCR7 and L-selectin, indicating that they are primarily antigen-experienced memory cells. Notably, nearly one-third of these cells express the HLA-DRA surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated αß T cells (CD4

Molecular Imaging of Inflammation in Ischemic Heart Disease.

PURPOSE OF REVIEW: Ischemic heart disease is caused by atherosclerosis, the build-up of plaque in the coronary arteries, which can lead to the development of heart attacks and heart muscle damage. Despite the advent of medical and surgical therapy to prevent and treat atherosclerosis and its adverse clinical effects, ischemic heart disease remains a leading cause of morbidity and mortality. Recent studies have suggested that the immune system may play a greater role in the development of plaque rupture and adverse left ventricular remodeling after myocardial infarction. Understanding the molecular processes by which inflammation contributes to the pathophysiology of ischemic heart disease is, therefore, worthwhile. This review focuses on new molecular imaging techniques to visualize immune cells to study their contribution to ischemic heart disease. RECENT FINDINGS: A common technique applied to imaging inflammation in ischemic heart disease is targeting the up-regulation and trafficking of immune cells, which may contribute to the adverse consequences associated with atherosclerosis. In the past five years, advances in cell labeling for imaging with PET and MRI, including radioisotopes and nanoparticles, have confirmed that inflammatory cells can be visualized in vivo and in greater abundance in unstable cardiovascular disease and in areas of ischemic damage. The major criticisms of these studies to date include their small sample size, lack of histological correlation, limited association with long-term outcomes, and bias toward macrophage imaging. SUMMARY: While much progress has been made in imaging inflammation in ischemic heart disease over the past five years, additional studies in larger cohorts with histological validation and outcome correlation are needed. Nevertheless, imaging inflammation using PET or MRI has the potential to become an important adjunct tool to improve the diagnosis, risk stratification, and therapeutic monitoring of patients with ischemic heart disease.

Brief Report: External Beam Radiation Therapy for the Treatment of Human Pluripotent Stem Cell-Derived Teratomas.

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs), have great potential as an unlimited donor source for cell-based therapeutics. The risk of teratoma formation from residual undifferentiated cells, however, remains a critical barrier to the clinical application of these cells. Herein, we describe external beam radiation therapy (EBRT) as an attractive option for the treatment of this iatrogenic growth. We present evidence that EBRT is effective in arresting growth of hESC-derived teratomas in vivo at day 28 post-implantation by using a microCT irradiator capable of targeted treatment in small animals. Within several days of irradiation, teratomas derived from injection of undifferentiated hESCs and hiPSCs demonstrated complete growth arrest lasting several months. In addition, EBRT reduced reseeding potential of teratoma cells during serial transplantation experiments, requiring irradiated teratomas to be seeded at 1 × 103 higher doses to form new teratomas. We demonstrate that irradiation induces teratoma cell apoptosis, senescence, and growth arrest, similar to established radiobiology mechanisms. Taken together, these results provide proof of concept for the use of EBRT in the treatment of existing teratomas and highlight a strategy to increase the safety of stem cell-based therapies. Stem Cells 2017;35:1994-2000.