Search PubMed⌕ Search

Biomedical subjects

A M Sun

Publications and source records attributed to A M Sun.

At least 55 records · Page 3Linked to original sources
PubMed1991

Prolonged reversal of diabetic state in NOD mice by xenografts of microencapsulated rat islets.

Transplantation of the islets of Langerhans could be the most promising approach to the clinical treatment of insulin-dependent (type I) diabetes mellitus. In this study, we report on a modified encapsulation technique that produces small alginate-polylysine capsules (0.25-0.35 mm diam). In an in vitro study, both encapsulated and unencapsulated islets showed comparable responses to glucose challenge in terms of insulin secretion. With the new capsules, 16 spontaneously diabetic NOD mice received transplants of 800 encapsulated rat islets/animal. Nonfasting blood glucose concentration decreased from 24.4 +/- 1.4 to 4.0 +/- 1.3 mM. At 4 and 5 mo posttransplantation, the capsules were removed from 2 recipients. Both animals regressed to a hyperglycemic state after capsule removal. However, after another islet transplantation, normoglycemia was again restored in these 2 animals. In control mice, which received unencapsulated islets, the xenografts remained functional for less than 10 days. A high mortality rate was observed among these animals within 2 mo of the recurrence of the hyperglycemic state. Our results clearly indicate that encapsulation of pancreatic islets in the improved capsules can effectively prolong xenograft survival without immunosuppression in an animal model that mimics human type I diabetes mellitus.

Animals↗
PubMed1990

Reversal of diabetes in BB rats by transplantation of encapsulated pancreatic islets.

Prolonged survival of pancreatic islet allografts implanted in diabetic BB rats was achieved by encapsulation of individual islets in a protective biocompatible alginate-polylysine-alginate membrane without immunosuppression. Intraperitoneal transplantation of the encapsulated islets reversed the diabetic state of the recipients within 3 days and maintained normoglycemia for 190 days. Normal body weight and urine volume were maintained during this period, and no cataracts were detected in the transplant recipients. In contrast, control rats receiving transplants of unencapsulated islets experienced normoglycemia for less than 2 wk. These results demonstrated that microencapsulation can protect allografted islets from both graft rejection and autoimmune destruction without immunosuppression in an animal model that mimics human insulin-dependent diabetes.

Alginates↗
PubMed1989

Development and evaluation of a system of microencapsulation of primary rat hepatocytes.

To determine the in vitro function of microencapsulated hepatocytes, viable hepatocytes were isolated from rats and encapsulated within biocompatible alginate-polylysine membranes for in vitro studies. Urea formation, prothrombin and cholinesterase activity, the incorporation of tritiated leucine into intracellular proteins and the immunolocation of synthesized albumin were monitored in culture. Despite a decrease in some of these activities, the cultured hepatocytes continued to function throughout the 5-week observation period, producing and excreting urea, prothrombin and cholinesterase activity into the medium. In addition, albumin could be demonstrated within encapsulated hepatocytes for up to 5 weeks. Scanning and transmission electron microscopy showed the cells to be embedded within the alginate matrix and to retain a globular shape.

Albumins↗
PubMed1989

Sodium-coupled ion cotransport and the volume regulatory increase response.

In conclusion, maintenance of volume homeostasis is a fundamental requirement of all cells. For many cell types, this process requires expression of ion cotransport mechanisms as well as accumulation of osmotically-active organic compounds. Recent observations have indicated that the cellular mechanisms responsible for modulating hypertonic volume regulation are complex and appear to involve hormonal, biochemical and physico-chemical stimuli. Knowledge of the specific ion-transport mechanisms involved in the initial phase of VRI, the factors that control their expression, and the interrelationships between inorganic and organic solute accumulation will be required before an in depth understanding of hypertonic cell volume regulation in medullary nephron segments can be achieved.

Animals↗
PubMed1989

Microencapsulated parathyroid cells as a bioartificial parathyroid. In vivo studies.

Parathyroid cells were isolated from healthy rats, encapsulated in alginate-polylysine membranes, and injected intraperitoneally into rats on which total parathyroidectomies had been performed. Three days posttransplant, serum calcium and PTH-M concentrations had increased to near-normal levels in the recipient animals. Similar results were observed in a separate group of parathyroidectomized rats 3 days after free parathyroid cells were implanted, but within 4 weeks serum calcium and PTH-M concentrations had decreased almost to pretransplant levels in these rats. In the rats with encapsulated cell transplants, by contrast, serum calcium and PTH-M levels were significantly higher, even after 8 weeks. No therapeutic effects were observed in rats injected with empty capsules or in the control group, which received no capsules or cells. These results indicate that transplants of microencapsulated parathyroid cells can temporarily reverse aparathyroidism in rats without the use of immunosuppressive drugs, and that further studies are warranted to investigate possible future clinical applications of this treatment.

Animals↗
PubMed1989

Stimulative effect of substance P on insulin secretion from isolated rat islets under normobaric oxygen incubation.

The effects of substance P (SP), physalaemin, and [D-Pro2, D-Phe7, D-Trp9]-SP on insulin release from isolated, cultured rat islets were investigated. Substance P stimulated insulin secretion in a dose-dependent manner at 0.1-100 nmol/L under one atmosphere of air with glucose 2.75, 5.5 and 20 mmol/L in the culture medium. Physalaemin 100 nmol/L was added to the culture medium, also stimulated insulin secretion. [D-Pro2, D-Phe7, D-Trp9]-SP 10 nmol/L reversed the stimulative effect of substance P. However, substance P 1 nmol/L inhibited insulin secretion from isolated rat islets under hyperbaric oxygen condations.

Animals↗
PubMed1988

Microencapsulation of pancreatic islet cells: a bioartificial endocrine pancreas.

It was about two decades ago that Chang proposed the use of microencapsulated islets as artificial beta cells. By using alginate-poly(L-lysine)-alginate membranes, biocompatible, durable capsules containing viable islet cells can be produced which are impermeable to cells and effector molecules of the immune system, thus providing a total protection to transplanted islets against rejection. The capsule wall contains 93% (w/w) water and can be classified as a hydrogel. Many hydrogels have gained general acceptance as being biocompatible materials. Microencapsulation of pancreatic islets for use as an artificial endocrine pancreas would not only obviate the need for immunosuppressive therapy but also has the potential to prevent the long-term complications of diabetes. Furthermore, the microencapsulation technique can be applied to other types of cells to produce antibodies or enzymes, and to treat a whole range of diseases requiring endocrine replacement therapy.

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↗
PubMed1987

Microencapsulated cells as hormone delivery systems.

Transplantation of pancreatic islets of Langerhans has been shown to prevent the development of many of the complications associated with diabetes. Transplanted islets, however, are readily rejected by the immune system. The use of artificial membranes to isolate the transplanted islets from the immune system of the host prolongs islet allografts in experimental animals. We have developed a method for encapsulating islets in semipermeable membranes composed of alginate and polylysine. The same technique can be applied to other endocrine cell types. The capsules are 700 to 800 micron in diameter with a hydrogel membrane approximately 4 micron thick. Intraperitoneal allografts of 5 x 10(3) encapsulated islets reversed diabetes in rats for up to 21 months and intact capsules with viable beta cells could be recovered from the recipients. Microencapsulation of endocrine cells for transplantation could potentially be used in the clinical treatment of hormone deficiency diseases.

Animals↗
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↗