Obstructive arterial disease is a major cause of morbidity and mortality in the developed world. Venous bypass graft surgery is one of the most frequently used revascularization strategies despite... Show moreObstructive arterial disease is a major cause of morbidity and mortality in the developed world. Venous bypass graft surgery is one of the most frequently used revascularization strategies despite its considerable short and long time failure rate. Due to vessel wall remodeling, inflammation, intimal hyperplasia, and accelerated atherosclerosis, vein grafts may (ultimately) fail to revascularize tissues downstream to occlusive atherosclerotic lesions. In the past decades, little has changed in the prevention of vein graft failure (VGF) although new insights in the role of innate and adaptive immunity in VGF have emerged. In this review, we discuss the pathophysiological mechanisms underlying the development of VGF, emphasizing the role of immune response and associated factors related to VG remodeling and failure. Moreover, we discuss potential therapeutic options that can improve patency based on data from both preclinical studies and the latest clinical trials. This review contributes to the insights in the role of immunomodulation in vein graft failure in humans. We describe the effects of immune cells and related factors in early (thrombosis), intermediate (inward remodeling and intimal hyperplasia), and late (intimal hyperplasia and accelerated atherosclerosis) failure based on both preclinical (mouse) models and clinical data. Show less
Cell transplantation studies have shown that injection of progenitor cells can improve cardiac function after myocardial infarction (MI). Transplantation of human cardiac progenitor cells (hCPCs)... Show moreCell transplantation studies have shown that injection of progenitor cells can improve cardiac function after myocardial infarction (MI). Transplantation of human cardiac progenitor cells (hCPCs) results in an increased ejection fraction, but survival and integration are low. Therefore, paracrine factors including extracellular vesicles (EVs) are likely to contribute to the beneficial effects. We investigated the contribution of EVs by transplanting hCPCs with reduced EV secretion. Interestingly, these hCPCs were unable to reduce infarct size post-MI. Moreover, injection of hCPC-EVs did significantly reduce infarct size. Analysis of EV uptake showed cardiomyocytes and endothelial cells primarily positive and a higher Ki67 expression in these cell types. Yes-associated protein (YAP), a proliferation marker associated with Ki67, was also increased in the entire infarcted area. In summary, our data suggest that EV secretion is the driving force behind the short-term beneficial effect of hCPC transplantation on cardiac recovery after MI. Show less
Intramyocardial bone marrow cell injection is currently being investigated as a new therapeutic option for the treatment of chronic myocardial ischemia. Experimental studies and early phase... Show moreIntramyocardial bone marrow cell injection is currently being investigated as a new therapeutic option for the treatment of chronic myocardial ischemia. Experimental studies and early phase clinical trials established a favorable safety profile of this approach and suggested that bone marrow cell injection was associated with clinical and functional improvements. Recently, a randomized, double-blind, placebo-controlled trial demonstrated that intramyocardial bone marrow cell injection was associated with beneficial effects on myocardial perfusion and anginal symptoms. However, the mechanisms by which bone marrow cells may improve myocardial perfusion are only partially understood, and several issues remain to be addressed. This review aims to provide a summary of the current experience with bone marrow cell therapy as a novel treatment option for patients with chronic myocardial ischemia. Therefore, the most frequently used cell types will be reviewed along with the mechanisms through which bone marrow cells may improve myocardial perfusion and function. In addition, possible routes of delivery are compared, and the results of currently available experimental and clinical studies are discussed. Show less
