Search PubMed⌕ Search

Biomedical subjects

W L Chick

Publications and source records attributed to W L Chick.

85 records · Page 5Linked to original sources
PubMed1969

Mitotic division in pancreatic beta cells.

Successful expansion of the islet cell mass occurs in genetically diabetic mice (C57 Bl/Ks-dbdb) following a period of dietary restriction, in the absence of a population of precursor cells. Differentiated cells that synthesize insulin retain the capability of undergoing mitotic division.

Animals↗
PubMedDate not supplied

Evaluation of the hybrid artificial pancreas in diabetic dogs.

Immunoisolation of nonsyngeneic tissue using a selectively permeable membrane is designed to facilitate transplantation without the use of immunosuppression. The authors' studies have evaluated a hybrid artificial pancreas device that is implanted as an arteriovenous vascular shunt. Devices containing allogeneic or xenogeneic islets were implanted in diabetic dogs who had undergone pancreatectomies, and the devices eliminated the requirement for exogenous insulin for control of fasting glycemia in 11 animals for periods ranging from 1 to 8 months. Furthermore, unseeded devices in normal dogs have been shown to remain patent for over 2 years with low doses of aspirin as the only anticoagulant. These results indicate that this approach has potential as a therapy for diabetes.

Animals↗
PubMedDate not supplied

Islet transplantation using an immunoprotective membrane in dogs that have undergone a pancreatectomy.

The use of a selectively permeable membrane to transplant nonsyngeneic tissue without accompanying immunosuppressive therapy has been investigated using two approaches. The first hybrid artificial pancreas is implanted as a vascular shunt in which blood circulates through the lumen of a tubular membrane. The islet tissue is distributed within a chamber surrounding the membrane enclosed by an acrylic housing. Studies with diabetic dogs that have had pancreatectomies have demonstrated that these devices could replace exogenous insulin therapy for at least 6 months in five animals. This report presents data on two of these dogs, demonstrating viability and function of the transplanted tissue after 1 year. As an alternative to the vascular device, islets sealed within cylindrical permselective membrane chambers have been implanted in the peritoneum. Preliminary data from three dogs indicate that the nonvascular implants can also regulate fasting glucose levels in the diabetic dog model.

Animals↗
PubMedDate not supplied

Secretory function of biohybrid pancreas devices containing isolated porcine islets.

Isolated porcine islets represent a potential source for discordant islet xenografts in diabetic patients. The authors therefore investigated insulin secretion from isolated porcine islets both in vitro and in vivo. For in vitro studies, islets were maintained in culture or placed in biohybrid perfusion devices consisting of a plastic housing containing a selectively permeable acrylic copolymer tubular membrane. Culture medium was circulated through the devices in a closed loop system. After 3 months the cultured islets secreted insulin at levels of 354 +/- 49 microU/equivalent islet number (EIN)/day (mean +/- standard error of the mean [SEM]; n = 10). They responded to glucose stimulation (5 to 16 mmol/L steps) with significant increases in insulin secretion. The biohybrid devices seeded with islets produced 23 +/- 2 (mean +/- SEM; n = 8) units insulin per day over periods of 83 +/- 8 days. For in vivo studies, islets were sealed within membrane chambers and implanted in the peritoneal cavity of streptozotocin induced diabetic Lewis rats. Chambers with a total of 2 x 10(4) islets per rat normalized the plasma glucose values of 10 rats, with the concentrations decreasing from 487 +/- 18 to 97 +/- 10 mg/dl during the first month. All grafts maintained normoglycemia for longer then 3 months. Histologic studies of long-term chamber implants in rats (1-20 months of age) showed viable islets, with varying degrees of beta cell granulation. These studies suggest the long-term functioning of porcine islets both in vitro and in vivo as discordant xenografts.

Animals↗
PubMedDate not supplied

Staining and in vitro toxicity of dithizone with canine, porcine, and bovine islets.

Dithizone (DTZ) is a recognized diabetogenic agent in vivo, and a supravital stain commonly used for identification of islets to be used for transplantation. In the present studies, we compared DTZ staining of freshly isolated and cultured canine, bovine, and porcine islets, and the effect of DTZ on the function and viability of islets. Incubation with DTZ resulted in staining of canine and porcine islets, but no discernible staining with bovine islets. Insulin content of porcine, canine, and bovine islet was 2.0 +/- 0.2, 2.2 +/- 0.3, and 1.9 +/- 0.2 mU/EIN, indicating a lack of correspondence of DTZ staining and insulin content. Seven days of culture with canine islets resulted in > or = 50% reduction of DTZ stained cells. Exposure to DTZ at 50 micrograms/mL resulted in a maximal number of stained cells in preparations of purified islets (80-85%; counted after dispersion), a lower percentage of cells stained faintly at 20 micrograms/mL (50-55%), with no discernible staining at 10 micrograms/mL. Prolonged exposure of islets (4-48 h) to 20 micrograms/mL DTZ led to reduced insulin secretion and islet cell death. Incubation of canine or porcine islets with 100 micrograms/mL of DTZ for 0.5 h resulted in a dramatic loss of viability and diminished insulin secretory function, which was not reversed with continued culture. The concentration dependence of toxic effects paralleled the concentration dependence of cellular staining. The minimally effective staining concentration (20 micrograms/mL) also resulted in a loss of viability. An additional assessment of DTZ toxicity was made using the RIN-38 beta-cell line, which shows no discernible staining with DTZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Relationship between insulin secretion and oxygen tension in hybrid diffusion chambers.

Oxygen tension is of potential importance in hybrid diffusion chambers, where both islet density and the site chosen for implantation can significantly affect the pO2 within the chambers. To investigate this, isolated islets were incubated at oxygen tensions of 38 mmHg ("low") and 154 mmHg ("ambient"). The mean (+/- SD) ratio between insulin secretion at low and at ambient oxygen tensions was 0.92 +/- 0.27 (n = 10) for porcine islets and 0.80 +/- 0.08 (n = 5) for canine islets. The pO2 was then determined in vivo in cylindrical diffusion chambers (inner diameter 4.5 mm) fabricated from acrylic copolymer, seeded with isolated porcine islets at densities of 0, 15, 30, and 45 islets/mm3, and implanted intraperitoneally in rats. The pO2 levels inside the chambers after 2 weeks were 57 +/- 6 (n = 12), 39 +/- 5 (n = 6), 38 +/- 6 (n = 6), and 43 +/- 3 (n = 6) mmHg, respectively. After 6 weeks, the results were 51 +/- 3 (n = 6), 26 +/- 8 (n = 3), 29 +/- 12 (n = 3), and 40 +/- 5 (n = 3) mmHg, respectively. In comparison, similar chambers containing 10 islets/mm3 cultured for 1 week at ambient oxygen had a pO2 of 120 +/- 9 (n = 4) mmHg immediately underneath the membrane and 67 +/- 7 (n = 4) mmHg at the axial center.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗