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Biomedical subjects

Ron Waksman

Publications and source records attributed to Ron Waksman.

204 records · Page 12Linked to original sources
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Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium.

Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

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Beta emitter systems and results from clinical trials. state of the art.

Vascular brachytherapy has been established as the standard of care for the treatment of in-stent restenosis (ISR). Both beta and gamma emitters are currently in use for the prevention of ISR recurrence. The use of beta sources for vascular application is attractive from both the radiation exposure and safety points of view, and a wide variety of beta sources are available for this application. This review is intended to summarize the clinical trials utilizing beta emitter systems for the treatment of ISR and de novo lesions and their subsequent results.

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Radiation-induced atherosclerotic plaque progression in a hypercholesterolemic rabbit: a prospective vulnerable plaque model?

PURPOSE: Human observations provide rich soil for making hypotheses, but good animal models are essential for understanding the disease and to test treatment modalities. Currently, there is no standard animal model of vulnerable plaque; therefore, the purpose of this study is to develop a pathophysiologically relevant vulnerable plaque model. METHODS: New Zealand White rabbits were fed with 1% hypercholesterolemic (HC) diet for 7 days, followed by balloon denudation of both the iliac arteries, and continued on 1% HC diet. Four weeks later, in 12 rabbits one of the iliac arteries was radiated (192-Ir, 15 Gy), and in five rabbits both the iliac arteries were sham treated. Following that, rabbits were fed with 0.15% HC diet. Four weeks later, arteries were processed for histomorphometry or immunohistochemistry. RESULTS: Serum cholesterol levels were similar in all the groups. In radiated arteries, plaque area was significantly larger (32% larger then in sham). Macrophage-positive area in radiated arteries was 2.4 times greater than the macrophage-positive area in the nonradiated arteries. The area positive for macrophages is also positive for metalloproteinases (MMP)-1. The extent of alpha-actin positive area was significantly less (2.3-fold) in radiated arteries. CONCLUSION: The atherosclerotic plaque developed in the current model is predominantly composed of macrophages expressing metalloproteinases with few smooth muscle cells (SMC)--a characteristic of vulnerable plaque. The animal model presented in this study can elucidate at least part of the mechanism of plaque vulnerability and could be used to test treatment modalities to test plaque stability.

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Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model.

HYPOTHESIS: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. METHODS: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. RESULTS: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63+/-1.99 vs. 4.77+/-.1.71 mm2, respectively, P<.05). CONCLUSION: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

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