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Biomedical subjects

G M O'Shea

Publications and source records attributed to G M O'Shea.

10 recordsLinked to original sources
PubMed1990

The fate of transplanted encapsulated islets in spontaneously diabetic BB/Wor rats.

The present study was undertaken to determine whether the transplantation of encapsulated MHC identical islets into diabetic BB/Wor/BB rats could cure their diabetes. Islets were isolated from diabetes-resistant BB/Wor/WB rats and encapsulated in alginate-polylysine-alginate membranes. Five thousand islets were transplanted into the peritoneal cavity of spontaneously diabetic BB/Wor/BB rats (n = 9) that had been insulin dependent for more than five weeks. Similar diabetic animals were transplanted with 5,000 unencapsulated islets (n = 10) or with empty capsules (n = 3). After transplantation of free islets, the animals reverted to the insulin-dependent state after a median of 16 days (17 +/- 4 days, mean +/- SEM). After transplantation of encapsulated islets, the animals reverted to the diabetic state after a median of 59 days (54 +/- 10 days, mean +/- SEM). Light microscopic and electron microscopic analyses of capsules recovered from the peritoneal cavity after failure of graft function showed no evidence either of lymphocytic invasion of the capsules or of specific destruction of the islets. The capsules were, however, overgrown by a layer of histiocytes and numerous layers of fibroblasts. Empty capsules recovered after 15 and 60 days were overgrown to the same extent.

Alginates↗
PubMed1988

Microencapsulated hepatocytes for bioartificial liver support.

Free hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, were encapsulated within alginate-polylysine membranes and served as a liver support system. The encapsulated hepatocytes remained viable and were able to synthesize protein for up to 3 weeks in culture. Allografts of encapsulated hepatocytes replaced the function of a damaged liver and reduced the mortality rate among rats with galactosamine-induced fulminant hepatic failure.

Albumins↗
PubMed1987

Microencapsulated hepatocytes: an in vitro and in vivo study.

Using a modified alginate-polylysine membrane, we have successfully encapsulated rat hepatocytes with little loss of viability. Urea and albumin release from encapsulated liver cells was comparable to that from non-encapsulated cells during the first 4 days in culture. Histological studies also showed that more than 50% of the encapsulated hepatocytes remained viable 35 days after implantation in the peritoneal cavity of both normal rats and rats with galactosamine induced fulminant hepatic failure. Transplantation of microencapsulated hepatocytes provides a potential clinical treatment for liver failure.

Albumins↗
PubMed1986

Encapsulation of rat islets of Langerhans prolongs xenograft survival in diabetic mice.

Rat islets encapsulated in alginate-polylysine membranes were implanted intraperitoneally into nonimmunosuppressed streptozocin-induced diabetic mice. Diabetes was reversed within 3 days, and the animals remained normoglycemic for up to 144 days, with a mean xenograft survival of 80 days. This was significantly greater than nonencapsulated islets, which functioned for less than 14 days. The graft survival rate at 50 days was greater than 80%. Xenografts of rat islets encapsulated in alginate-polyornithine membranes also had a prolonged survival rate. This study demonstrates that encapsulation of pancreatic islets in semipermeable membranes can prolong xenograft survival in the absence of immunosuppression.

Alginates↗
PubMed1984

Prolonged survival of transplanted islets of Langerhans encapsulated in a biocompatible membrane.

Prolonged survival of islet allografts in streptozotocin-induced diabetic rats was achieved by encapsulating individual islets in protective, biocompatible alginate-polylysine-alginate membranes. A single intraperitoneal transplant of encapsulated islets reversed the diabetic state for up to 1 year. In contrast, a single injection of unencapsulated islets was effective for less than 2 weeks. The microencapsulation procedure, by protecting transplanted tissue from the components of the immune system, has great clinical potential in the treatment of diseases requiring organ transplantation, such as diabetes and liver disease.

Alginates↗
PubMed1984

Injectable microencapsulated islet cells as a bioartificial pancreas.

Rat islets encapsulated in semipermeable membranes remained viable in culture for 4 months. Multiple allotransplants of islets encapsulated in alginate-polylysine-polyethyleneimine membranes restored normoglycemia in recipient diabetic rats for most of a 90-day experimental period. Each individual transplant restored normal fasting plasma glucose levels for 15-20 d. The failure of the encapsulated islets was caused by an inflammatory response induced by polyethyleneimine. In contrast a single transplant of islets encapsulated in a biocompatible alginate-polylysine-alginate membrane restored normoglycemia in recipient animals for up to 10 months. Capsules with intact membranes and containing viable islets were recovered from the abdominal cavity 5 months post-transplantation. SEM studies on capsule membranes revealed essentially smooth surfaces. Differences between wet and dry wall thicknesses indicated that the membrane is a hydrogel, 4.00 +/- 0.28 micron thick in an aqueous environment. The clinical potential of transplanting cells encapsulated in biocompatible semipermeable hydrogel membranes is demonstrated by this study.

Animals↗
PubMed1983

Microencapsulation of crystalline insulin or islets of Langerhans: an insulin diffusion study.

Microcapsules containing insulin crystals or islets of Langerhans were made by extruding a mixture of insulin crystals or islets and sodium alginate into a calcium chloride solution, and then coating it with poly-l-lysine. When these microcapsules were incubated at 37 degrees C, insulin could be detected readily in the medium, indicating that the microcapsular membrane is permeable to insulin. The efficiency of insulin encapsulation with crystalline insulin declined as the concentration in the sodium alginate mixture increased. Over 90% of the entrapped insulin was released after 3 days of incubation at 37 degrees C, indicating that the rate of insulin release from the microcapsules requires modification if the microcapsules are to be used as a long-term insulin delivery system. The amount of insulin secreted by the encapsulated islets was not significantly different from that of unencapsulated islets, suggesting the islets were not affected by the modified encapsulation process.

Alginates↗
PubMed1983

Slow release of insulin from a biodegradable matrix implanted in diabetic rats.

This report describes the development of a long-acting insulin accomplished by the slow release of hormone from an implantable, biodegradable matrix. Rats made diabetic with streptozotocin received a single subcutaneous implant of insulin-albumin microbeads that released biologically active insulin for periods up to 3 wk. The mean fasting blood glucose level for treated animals was 88 mg/dl as compared with 392 mg/dl for untreated diabetic controls. With a mean starting body weight of 187 g, treated animals gained weight reaching a mean weight of 228 g; in contrast, untreated animals lost weight to a mean of 175 g. When insulin-albumin microbeads were periodically implanted and removed, lower blood glucose levels were only associated with the presence of the implants. The microbead implants biodegraded in 4-8 wk, thus obviating the need for surgical removal. These results suggest that a long-acting insulin may be produced by the entrapment of insulin within a biodegradable matrix.

Animals↗