Transplantation of enterocytes utilizing polymer-cell constructs to produce a neointestine.
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Animals↗
Biomedical subjects
D J Mooney
Publications and source records attributed to D J Mooney.
Welding arc maculopathy and fluphenazine.
A 45-year-old male patient presented with a bilateral maculopathy following unprotected exposure of less than two minutes' duration to a manual metal arc welding unit. He had been receiving the drug fluphenazine for the previous 10 years for treatment of depression. We believe that the drug fluphenazine, which had accumulated in his retinal pigment epithelium, may have rendered him particularly susceptible to retinal photic damage.
Fluphenazine↗
Deciphering bloody imprints through chemical enhancement.
Obliterated bloody impressions are occasionally submitted to the crime laboratory, and potentially to the document examiner, for decipherment. Nondestructive methods often lead to inconclusive results in these circumstances. With this point in mind, the researchers explored a series of chemical reagents with the intent to enhance bloody imprints to a legible degree. The reagents selected for this comparison include rhodamine dye, luminol, and Coomassie Blue stain.
Blood Stains↗
Anaphylaxis following oral fluorescein angiography.
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Administration, Oral↗
Angioid streaks in beta thalassaemia minor.
We report what we believe to be the first recorded case of angioid streaks in a patient with beta thalassaemia minor. The occurrence of angioid streaks in a patient with a relatively normal iron balance and only very mild haemolysis may be explained by the combination of pregnancy with associated multiple transfusions in a myopic patient where an inherent defect in Bruch's membrane may exist.
Adult↗
Retinal function in Stargardt's disease and fundus flavimaculatus.
Ten patients with Stargardt's disease and 14 with fundus flavimaculatus underwent thorough ophthalmic examinations, retinal photography, and, when possible, fluorescein angiography. Retinal function was also assessed by static and kinetic perimetry, the Farnsworth-Munsell 100-hue test, electro-oculography, and electroretinography. Visual acuity and color discrimination were reduced in all patients (mean visual acuity, 20/120; mean error score, 365). On electroretinography all patients had some significant abnormality of cone function and 24 eyes had abnormal rod function (mean Vmax, 298.3). Electrooculographic findings were abnormal in 24 eyes and borderline in ten others. These abnormalities were similar in both groups but more severe in fundus flavimaculatus. Stargardt's disease and fundus flavimaculatus did not co-exist in any family studied and the mean duration of disease was similar in both, indicating that Stargardt's disease did not progress to fundus flavimaculatus. Both the age of onset and duration significantly affected the severity of fundus flavimaculatus but neither had a significant effect on Stargardt's disease.
Adolescent↗
The additional pressure-lowering effect in patients with glaucoma of pilocarpine 2 per cent, adrenaline 1 per cent, or guanethidine 3 per cent with adrenaline 0.5 per cent and timolol 0.25 per cent: a double-blind cross-over study.
A group of twelve comparable patients with primary open angle glaucoma were treated with Timolol 0.25 per cent drops to which was added pilocarpine 2 per cent, adrenaline 1 per cent or guanethidine 3 per cent plus adrenaline 0.5 per cent in a cross-over study. The initial intraocular pressure (IOP) reduction due to timolol was statistically significant. The mean additional IOP lowering due to pilocarpine 2 per cent was 1.37 mm Hg, that due to adrenaline 1 per cent was 1.79 mm Hg and that due to guanethidine 3 per cent plus adrenaline 0.5 per cent was 5.29 mm Hg.
Aged↗
Basal skin resistance of premature infants.
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Arousal↗
Congenital keratolenticular adhesion.
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Anterior Chamber↗
The pattern ERG in Best's disease.
The aim of this study was to assess inner retinal function in patients with Best's disease using the pattern ERG (PERG). Nine patients with Best's disease, who had good visual acuity, were studied. Five of the nine had abnormal PERGs. All five had some reduction in central visual acuity. We believe that the abnormal PERGs in these patients represents photoreceptor cell loss which is occurring at an early stage in Best's disease.
Adult↗
Regenerative signals for tissue-engineered small intestine.
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Animals↗
Degradation of partially oxidized alginate and its potential application for tissue engineering.
Alginate has been widely used in a variety of biomedical applications including drug delivery and cell transplantation. However, alginate itself has a very slow degradation rate, and its gels degrade in an uncontrollable manner, releasing high molecular weight strands that may have difficulty being cleared from the body. We hypothesized that the periodate oxidation of alginate, which cleaves the carbon-carbon bond of the cis-diol group in the uronate residue and alters the chain conformation, would result in promoting the hydrolysis of alginate in aqueous solutions. Alginate, oxidized to a low extent (approximately 5%), degraded with a rate depending on the pH and temperature of the solution. This polymer was still capable of being ionically cross-linked with calcium ions to form gels, which degraded within 9 days in PBS solution. Finally, the use of these degradable alginate-derived hydrogels greatly improved cartilage-like tissue formation in vivo, as compared to alginate hydrogels.
Absorbable Implants↗
Engineering dental pulp-like tissue in vitro.
Injury or infection of adult dental pulp often necessitates root canal therapy. This terminates dentin formation and subsequent tooth maturation. In addition, the synthetic materials currently utilized to replace lost tooth structure are not capable of completely replacing the function of the lost tissue, and often fail over time. This report describes a technique to engineer new pulp-like tissues utilizing cultured cells and synthetic extracellular matrices. Fibroblasts were obtained from human adult dental pulps and multiplied in culture. These cells were subsequently seeded onto synthetic matrices fabricated from fibers (approximately 15 microns in diameter) of polyglycolic acid (PGA). The pulp-derived fibroblasts adhered to the fibers, proliferated, and formed a new tissue over 60 days in culture with a cellularity similar to that of native pulp. These tissues may find application in the regeneration of oral tissues and may provide novel systems in which to study the biocompatibility of materials and chemicals used in dentistry.
Adult↗
Development of technologies aiding large-tissue engineering.
There are many clinical situations in which a large tissue mass is required to replace tissue lost to surgical resection (e.g., mastectomy). It is possible that autologous cell transplantation on biodegradable polymer matrices may provide a new therapy to engineer large tissue which can be used to treat these patients. A number of challenges must be met to engineer a large soft tissue mass. These include the design of (1) a structural framework to maintain a space for tissue development, (2) a space-filling matrix which provides for localization of transplanted cells, and (3) a strategy to enhance vascularization of the forming tissue. In this paper we provide an overview of several technologies which are under development to address these issues. Specifically, support matrices to maintain a space for tissue development have been fabricated from polymers of lactide and glycolide. The ability of these structures to resist compressive forces was regulated by the ratio of lactide to glycolide in the polymer. Smooth muscle cell seeding onto polyglycolide fiber-based matrices has been optimized to allow formation of new tissues in vitro and in vivo. Finally, polymer microsphere drug delivery technology is being developed to release vascular endothelial growth factor (VEGF), a potent angiogenic molecule, at the site of tissue formation. This strategy, which combines several different technologies, may ultimately allow for the engineering of large soft tissues.
Animals↗
Controlled growth factor release from synthetic extracellular matrices.
Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.
Alginates↗
Thrombospondin-1 induces endothelial cell apoptosis and inhibits angiogenesis by activating the caspase death pathway.
Thrombospondin-1 (TSP1) is a potent natural inhibitor of angiogenesis. Although TSP1 has been reported to induce endothelial cell apoptosis in vitro and to downregulate neovascularization in vivo, the molecular mechanisms that link these two processes have yet to be established. Here we report that TSP1 mediates endothelial cell apoptosis and inhibits angiogenesis in association with increased expression of Bax, decreased expression of Bcl-2, and processing of caspase-3 into smaller proapoptotic forms. The ability of TSP1 to induce both endothelial cell apoptosis in vitro and to suppress angiogenesis in vivo was blocked by the caspase-3 inhibitor z-DEVD-FMK. TSP1 also attenuated VEGF-mediated Bcl-2 expression in endothelial cells in vitro and angiogenesis in vivo. Furthermore, TSP1 induced endothelial cell apoptosis and inhibited neovascularization in sponge implants in SCID mice. We conclude that TSP1 induces endothelial cell apoptosis and inhibits neovascularization by altering the profile of survival gene expression and activating caspase-3.
3T3 Cells↗
Design and fabrication of biodegradable polymer devices to engineer tubular tissues.
Engineering new tissues by transplanting cells on polymeric delivery devices is one approach to alleviate the vast shortage of donor tissue. However, it will be necessary to fabricate cell delivery devices that deliver cells to a given location and promote the formation of specific tissue structures from the transplanted cells and the host tissue. This report describes the design and fabrication of a polymeric device for guiding the development of tubular vascularized tissues, which may be useful for engineering a variety of tissues including intestine, blood vessels, tracheas, and ureters. Porous films of poly (D, L-lactic-co-glycolic acid) have been formed and fabricated into tubes capable of resisting compressional forces in vitro and in vivo. These devices promote the ingrowth of fibrovascular tissue following implantation into recipient animals, resulting in a vascularized, tubular tissue. To investigate the utility of these devices as cell delivery devices, enterocytes (intestinal epithelial cells) were seeded onto the devices in vitro. Enterocytes were found to attach to these devices and form an organized epithelial cell layer. These results suggest that these devices may be an appropriate delivery vehicle for transplanting cells and engineering new tubular tissues.
Animals↗
Highly porous polymer matrices as a three-dimensional culture system for hepatocytes.
Hepatocyte-based therapies (e.g., hepatocyte transplantation and extracorporeal support devices) may provide alternative therapies to treat patients with liver disease, but suitable approaches to localize these cells to a given location while maintaining liver-specific gene expression must be developed. The suitability of highly porous three-dimensional sponges fabricated from poly (L-lactic acid) [PLLA] as an hepatocyte culture system was evaluated in this study. Sponges were fabricated utilizing a particulate leaching technique, and were approximately 95% porous, with an average pore diameter of 180 microns. Hepatocytes seeded into these sponges adhered and remained viable for 14 days. However, the secretion rate of albumin from these cells, an indication of liver-specific gene expression, was low (approximately 6 pg/cell/day at day 1), and decreased steadily over the 14 days of the experiment. Coating sponges with collagen, and more preferably, immobilizing cells within the PLLA sponges with a collagen gel, led to enhanced cell survival and albumin secretion at all time points. These data suggest that porous PLLA sponges may provide a novel system for long-term culture of hepatocytes, and proper design of the system may allow the liver-specific gene expression of hepatocytes transplanted in these matrices to be enhanced.
Albumins↗