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Clinical Trials of Hematopoietic Stem Cells for Cardiac and Peripheral Vascular Diseases
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Preclinical studies have indicated that angiogenic growth factors promote the development of collateral arteries, a concept called “therapeutic angiogenesis”.2 Angiogenesis can be achieved either by the use of growth factor proteins or genes encoding these proteins. Limited clinical data from protein- and gene-delivery trials suggested that both approaches are safe. However, a great deal more clinical experience will be necessary to resolve the safety concerns such as potentiation of pathological angiogenesis (e.g., malignancy) and “bystander” effects of the delivered factors (e.g., effects on kidney or atheroma).3 Given the investment of the formed mature vessels with periendothelial matrix and pericyte/smooth muscle cells, combinations of various angiogenic growth factors may be preferable in future therapies.
Imaging Angiogenesis
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Careful interpretation of these results revealed few potential factors found attributable to this unexpected failure, including suboptimal delivery strategies, use of a single growth factor at suboptimal dose, and duration of the therapy, which could lead to insufficient growth of new vessels or formation of nonfunctional vessels. Moreover, the evaluation of therapeutic angiogenesis in these trials was performed using rather insensitive techniques and focused on several clinical endpoints, including exercise tolerance, measures of quality of life and survival, peripheral pressure measurements, and imaging of tissue perfusion. Therefore, in recent years more focus was placed on the development of both novel therapeutic strategies, including genetic and cell-based approaches, and novel noninvasive imaging techniques to evaluate molecular events associated with angiogenesis (Dobrucki and Sinusas 2005a,b; Morrison and Sinusas 2010).
The role of the interventionalist in peripheral vascular interventions
Published in Ever D. Grech, Practical Interventional Cardiology, 2017
Alfred Hurley, Jayant Khitha, Tanvir Bajwa
Therapeutic angiogenesis is a type of gene therapy aimed at creating new mature collateral vessels to better perfuse an ischaemic limb. Early trials have been encouraging; however, only a modest benefit has been observed. Studies are ongoing as long-term effects are not yet known.25
Therapeutic angiogenesis in coronary artery disease: a review of mechanisms and current approaches
Published in Expert Opinion on Investigational Drugs, 2021
Bharat Narasimhan, Harish Narasimhan, Marta Lorente-Ros, Francisco Jose Romeo, Kirtipal Bhatia, Wilbert S. Aronow
A fundamental response of ischemic tissues, is the generation of new collateral vessels in an effort to overcome obstruction. This process is however often insufficient to provide a clinically meaningful mitigation of ischemia. The goal of therapeutic angiogenesis is to develop a more ‘physiological bypass’ by stimulating the de novo formation of new coronary vessels. Earliest recognition of this phenomenon dates back to 1939 when Sandison and colleagues [1234] postulated the existence of vascular growth factors that aid in angiogenesis within tumors – this laid the foundation for the isolation of vascular endothelial growth factor by Ferrara et al. nearly half a century later in 1989 [5]. In recent years, oncologic research into mechanisms of neovascularization in tumors has helped improve our basic understanding of this process and the pathways involved. This has been successfully extrapolated to a cardiovascular setting mainly in animal models, with limited success in humans. The sheer scale of benefits and paradigm shift that successful therapeutic angiogenesis could afford explains the continued interest in this challenging field. In this paper, we provide a comprehensive overview of the current state of therapeutic coronary angiogenesis. Following a brief description of the mechanisms involved in neonatal and adult neovascularization, we proceed to outline the various approaches that have been studied with a review of the clinical data supporting their use.