Biomedical subjects

S K Williams

Publications and source records attributed to S K Williams.

113 records · Page 7Linked to original sources

PubMedDate not supplied

Endothelial cell transplantation.

Endothelial cells line the lumenal surface of all elements of the vascular system. These cells exhibit numerous metabolic functions necessary for the maintenance of homeostasis. The critical role of endothelium in maintaining normal blood vessel function is exemplified by the poor clinical performance of small diameter polymeric vascular grafts which fail due, in part, to the lack of a functional endothelium on the lumenal surface. Extensive research has explored the potentiality of transplanting endothelial cells onto polymeric vascular grafts to improve graft function. Several critical issues have been explored including the source of endothelial cells for transplantation, the interaction of endothelium with polymers and the healing process of endothelial cell transplanted grafts. The future of endothelial cell transplantation will also include the use of these cells as vehicles for genetic engineering.

Adipose Tissue↗

PubMedDate not supplied

The neointima formed in endothelial cell sodded ePTFE vascular grafts results from both cellular-hyperplasia and extracellular-hypertrophy.

Endothelial cell transplantation onto polymeric vascular grafts results in the formation of a neointima. The formation of this neointima is often suggested to result from a chronic cellular hyperplasia where the terms intimal hyperplasia and intimal thickening are used interchangeably. While the formation of a midgraft neointima in sodded grafts involves a level of cell proliferation, the synthesis and deposition of extracellular matrix proteins is also a ubiquitous observation in these grafts. To assess the composition of midgraft neointima in sodded grafts, a morphometric method was developed to provide a differential quantitation of the cellular-hyperplastic and extracellular-hypertrophic elements of intimal thickening. The formed neointima on microvessel endothelial cell sodded and control (noncell-treated) ePTFE vascular grafts was quantified after 3, 12, and 52 wk of graft implantation in a canine carotid artery model. Midgraft sections of grafts were evaluated for both intimal thickness (IT) and cell density per unit volume and quantified using a PC-based image analysis program. Sodded grafts explanted at 3 wk exhibited an average neointimal cell density (3 x 10(9) cells/cm3; IT 30 microns) equivalent to cell densities observed in normal arterial media. After 12 wk the mean cell density approached a hyperplastic value (3.7 x 10(9) cells/cm3; IT 76 microns), while grafts explanted after 52 wk exhibited a mean cell density (2.8 x 10(9) cells/cm3; IT 30 microns) similar to 3-wk values. Control grafts that received no cells exhibited no midgraft cellular coverage. These results indicate that neointima formation in the midgraft region of sodded grafts occurred via mechanisms involving both a cellular hyperplasia and an extracellular hypertrophy. Differential responses occur presumably due to localized differences in cellular proliferation and cellular biosynthetic activity.

Animals↗

PubMedDate not supplied

Transfer and expression of the interferon gamma gene in human endothelial cells inhibits vascular smooth muscle cell growth in vitro.

Intimal hyperplasia in blood vessels is primarily caused by the migration and proliferation of vascular smooth muscle cells. Excessive intimal thickening characterizes atherosclerosis as well as bypass graft and angioplasty failures. Endothelial cell-smooth muscle cell interactions and local cytokine production are important regulators of smooth muscle cell growth. Interferon gamma (gamma-IFN), a product of T lymphocytes found in atherosclerotic lesions, inhibits smooth muscle cell proliferation in vitro. To determine if local delivery of gamma-IFN may be useful in the treatment or prevention of vascular proliferative diseases, we transferred the human gamma-IFN gene into endothelial cells isolated from human arteries and microvessels using a retroviral vector. Biologically active gamma-IFN was produced and secreted by gamma-IFN transduced endothelial cells, but not by control, nontransduced cells, or cells identically transduced with E. coli beta galactosidase (beta-gal). To more closely approximate the microenvironment of blood vessels, subconfluent smooth muscle cells were plated in coculture with control, nontransduced endothelial cells, gamma-IFN transduced endothelial cells, or beta-gal transduced endothelial cells. Smooth muscle cell growth was inhibited 30-70% by coculture with gamma-IFN transduced endothelial cells compared to coculture with beta-gal transduced or control endothelial cells (p < 0.05). Our results suggest endothelial cells modified to produce gamma-IFN may be a useful therapy in proliferative vascular diseases.

Cell Division↗

PubMedDate not supplied

Endothelial cell transplantation onto polymeric arteriovenous grafts evaluated using a canine model.

Prosthetic arteriovenous grafts (AVG) placed for hemodialysis access fail in humans due to the thrombogenicity of the flow surface and development of cellular intimal hyperplasia, particularly at the venous anastomosis. The poor patency rates of prosthetic AVG result in significant morbidity and mortality in dialysis patients. Consequently, investigators have been evaluating methods to improve the patency of prosthetic grafts by examining endothelial cell transplantation as a means of creating an antithrombogenic lining on artificial polymers. A canine model was developed to study the effects of cell transplantation of autologous, fat-derived microvessel endothelial cells (MVEC) onto the luminal surface of expanded polytetrafluoroethylene (ePTFE) grafts. Microvessel endothelial cells were isolated from falciform ligament fat, with each dog receiving its own endothelial cells. Isolated cells were subsequently placed into the lumen of the graft (4 mm by 20 cm ePTFE). The graft lumen was pressurized to 5 pounds per square inch (psi) resulting in the partial denucleation of the graft, due to the flow of buffer into the interstices of the graft, and the forced deposition of cells onto the luminal surface. Animals were maintained on aspirin and persantine during the implant phase. During the implant phase, grafts were evaluated by both duplex ultrasound and magnetic resonance angiography (MRA). At explant, gross observation of the sodded grafts revealed a glistening white flow surface with no evidence of thrombosis. Morphologic and scanning electron microscopic evaluations revealed the presence of a cellular lining on the luminal flow surface that exhibited characteristics of antithrombogenic endothelial cells. Midgraft samples were evaluated by immunocytochemistry and indicated that cells on the luminal surface react positively with antibodies to von Willebrand factor. Results from this study demonstrate that the canine model provides an excellent method of studying the effects of MVEC sodding on the thrombogenicity and hyperplastic response of prosthetic arteriovenous graft.

Animals↗

PubMedDate not supplied

Rapidly-frozen, cultured, human endothelial cells: an ultrastructural and morphometric comparison between freshly-frozen and glutaraldehyde prefixed cells.

Cultured, human endothelial cells from the iliac vein were divided into two groups for rapid-freezing using liquid helium in a Heuser-type cryopress freezing machine. The first group of cells was prefixed in buffered 2% glutaraldehyde solution whereas the second group was freshly-frozen. Following freeze substitution and embedding, morphometric analysis was carried out on thin sections of groups of endothelial cells. Measurements showed that glutaraldehyde prefixation significantly increases the numerical and volume densities of the vesicles compared to those of the freshly-frozen cells. However, the fact that no significant increase was demonstrated either in the numerical or volume densities of the caveolae, and that no significant change was observed in the ratio of the cell perimeter to area, suggests that the membrane source for these extra vesicles is internally generated. Studies are currently under way to identify the source of this membrane.

Cells, Cultured↗