Biomedical subjects

Helen M Nugent

Publications and source records attributed to Helen M Nugent.

3 recordsLinked to original sources

PubMed2005

Matrix embedding alters the immune response against endothelial cells in vitro and in vivo.

BACKGROUND: Endothelial cell (EC) dysfunction represents the first manifestation of atherosclerotic disease. Restoration of endothelium via seeding or transfection is hampered by local alterations in flow, inflammation, and metabolic activation. Perivascular EC matrix implants are shielded from these forces and still control vascular repair. The host immune response to such implants, however, remains largely unknown. We investigated the effect of embedding of ECs within 3-dimensional matrices on host immune responses in vitro and in vivo. METHODS AND RESULTS: We compared expression of major histocompatibility complex (MHC), costimulatory, and adhesion molecules by free aortic ECs or ECs embedded in Gelfoam matrices by flow-cytometry. T-cell proliferation was assessed by [3H] thymidine incorporation. Humoral immune response (ELISA and FACS analysis) and cellular (histopathology) infiltration were investigated after subcutaneous injection of free porcine aortic ECs (PAEs) or of a Gelfoam/EC block, or after concomitant injection of PAEs adjacent to Gelfoam in rats. Aortic ECs embedded in Gelfoam expressed lower levels of MHC class II, costimulatory, and adhesion molecules compared with free ECs (P<0.001), and induced 3-fold less proliferation of human CD4+ T-cells (P<0.0005). Implantation of a Gelfoam/EC block in rats nearly abrogated the immune response with 1.75- to 9.0-fold downregulation in tumor necrosis factor-alpha, interleukin-6, monocyte chemotactic protein-1, and PAE-specific immunoglobulin G (P<0.005) and 3.3- to 4.5-fold reduction in leukocytic tissue infiltration. Injecting PAEs adjacent to Gelfoam induced a significant response comparable to that of free implanted PAEs. CONCLUSIONS: Embedding ECs within 3-dimensional matrices alters the host immune response by inhibiting expression of MHC class II, costimulatory, and adhesion molecules, offering the rationale to develop novel therapies for vascular diseases.

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PubMed2003

Tissue engineering therapy for cardiovascular disease.

The present treatments for the loss or failure of cardiovascular function include organ transplantation, surgical reconstruction, mechanical or synthetic devices, or the administration of metabolic products. Although routinely used, these treatments are not without constraints and complications. The emerging and interdisciplinary field of tissue engineering has evolved to provide solutions to tissue creation and repair. Tissue engineering applies the principles of engineering, material science, and biology toward the development of biological substitutes that restore, maintain, or improve tissue function. Progress has been made in engineering the various components of the cardiovascular system, including blood vessels, heart valves, and cardiac muscle. Many pivotal studies have been performed in recent years that may support the move toward the widespread application of tissue-engineered therapy for cardiovascular diseases. The studies discussed include endothelial cell seeding of vascular grafts, tissue-engineered vascular conduits, generation of heart valve leaflets, cardiomyoplasty, genetic manipulation, and in vitro conditions for optimizing tissue-engineered cardiovascular constructs.

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PubMedDate not supplied

Perivascular endothelial implants inhibit intimal hyperplasia in a model of arteriovenous fistulae: a safety and efficacy study in the pig.

Vascular access complications are a major problem in hemodialysis patients. Native arteriovenous fistulae, historically the preferred mode of access, have a patency rate of only 60% at 1 year. The most common mode of failure is due to progressive stenosis at the anastomotic site. We have previously demonstrated that perivascular endothelial cell implants inhibit intimal thickening following acute balloon injury in pigs and now seek to determine if these implants provide a similar benefit in the chronic and more complex injury model of arteriovenous anastomoses. Side-to-side femoral artery-femoral vein anastomoses were created in 24 domestic swine and the toxicological, biological and immunological responses to allogeneic endothelial cell implants were investigated 3 days and 1 and 2 months postoperatively. The anastomoses were wrapped with polymer matrices containing confluent porcine aortic endothelial cells (PAE; n = 14) or control matrices without cells (n = 10). PAE implants significantly reduced intimal hyperplasia at the anastomotic sites compared to controls by 68% (p < 0.05) at 2 months. The beneficial effects of the PAE implants were not due to differences in the rates of reendothelialization between the groups. No significant immunological response to the allogeneic endothelial cells that impacted on efficacy was detected in any of the pigs. No apparent toxicity was observed in any of the animals treated with endothelial implants. These data suggest that perivascular endothelial cell implants are safe and reduce early intimal hyperplasia in a porcine model of arteriovenous anastomoses.

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