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Biomedical subjects

A M Sun

Publications and source records attributed to A M Sun.

71 records · Page 4Linked to original sources
PubMed1982

Insulin-albumin microbeads: an implantable, biodegradable system.

A feasibility study on developing an implantable, biodegradable insulin delivery system was carried out. Insulin-albumin microbeads (50-1,000 microns diameter) were implanted in diabetic rats. After a single subcutaneous implant of the glutaraldehyde crosslinked microbeads, elevated blood-insulin levels were detected in the diabetic animals for longer than two months. While the blood-insulin levels of the treated animals were sustained between 10 and 67 microU/ml during the initial two month post-implantation period, complete in-vivo biodegradation of the microbeads took longer than five months. The diabetic animals, with the insulin-albumin microbead implants, gained weight. In contrast, untreated diabetic controls lost weight. Fibrous capsules were found to have surrounded the microbeads when the implants were recovered at one and two months post-implantation. The results suggest that the fibrous capsules played a role in retarding insulin release from the albumin microbead system. Cross-linked serum albumin microbeads have the clinical potential of providing long-term in-vivo drug release. This system has the additional advantage of being biodegradable and also provides more options for the method and site of implantation.

Animals↗
PubMed1982

Ultrastructural differentiation in the nude mouse of transformed cells isolated from the human fetal pituitary gland.

Spontaneously transformed human fetal pituitary cells were isolated from first-passage cultures after 3 to 6 months of long-term maintenance in growth medium containing 15% fetal calf serum. The cells, when injected into nude mice, developed into large tumors in 1 to 2 weeks. Attempts to detect growth hormone, prolactin, follicle-stimulating hormone, luteinizing hormone, or thyroid-stimulating hormone from nude mouse plasma and tumor homogenate by radioimmunoassay were unsuccessful. These hormones could not be demonstrated in tumor cell cytoplasm by immunocytochemistry. Two human fetal pituitary (HFP) cell strains (HFP-T2, HFP-F4) from tissue culture examined at the electron microscopic level were undifferentiated by ultrastructural criteria. However, tumor cells in the nude mice showed signs of fine structural differentiation with well-developed rough endoplasmic reticulum profiles, secretory granules, and intercellular junctions. The tumor cells lost the features of morphological differentiation when returned to tissue culture. These changes could be repeated by alternate passage in nude mouse and tissue culture.

Animals↗
PubMed1981

Oncogenic transformation and the reductions of insulin secretion and proliferative calcium dependence during repeated passage of pancreatic islet cells in vitro.

Islet cells were isolated from 2 fetal bovine pancreas glands and cultivated in vitro. During the course of repeated passage in vitro, the B-cells in these cultures retained the ability to synthesize insulin, but rapidly lost the ability to secrete it. The cells also became progressively more able to proliferate in calcium-deficient medium which did not support the proliferation of cells from primary cultures. The reductions of insulin secretion and proliferative calcium dependence were accompanied by the acquisition of the ability to produce tumors in nude mice.

Animals↗
PubMed1980

Microencapsulated islets as bioartificial endocrine pancreas.

Single implantation of microencapsulated islets into rats with streptozotocin-induced diabetes corrected the diabetic state for 2 to 3 weeks. The microencapsulated islets remained morphologically and functionally intact throughout long-term culture studies lasting over 15 weeks.

Alginates↗
PubMed1977

The use, in diabetic rats and monkeys, of artificial capillary units containing cultured islets of Langerhans (artificial endocrine pancreas).

A unit was constructed that consisted of a core of hollow fibers through which low-molecular-weight substances, such as glucose and insulin, could pass freely but were impermeable to high-molecular-weight proteins, such as antibodies. Islets of Langerhans from normal rats were planted in the space surrounding the fibers, and either blood or nutrient medium was circulated through the fibers themselves. In experiments with animals, the units were attached to the vascular system of diabetic rats and monkeys. Blood glucose concentrations in the rats were reduced to nondiabetic levels within one hour and were maintained for the duration of the experiments. In monkeys the blood glucose level declined from 210 mg./100 ml. to 90 mg./100 ml. in four hours and insulin in the serum rose to 93 muU./ml. in one-half hour. Also, we have found that islets from monkeys cultivated in the artificial endocrine pancreas (AEP) continue to release insulin into circulating tissue culture medium for over eight months.

Animals↗
PubMedDate not supplied

Preliminary report on microencapsulated islet transplantation in experimental diabetes mellitus in China.

Pancreatic islets were encapsulated with sodium alginate-polylysine after procurement by collagenase digestion and Ficoll density-gradient-dispersion. The encapsulated islets were intact and during the first week of culture produced insulin 63 +/- 42 microU/d vs 69 +/- 42 microU/d by noncapsulated islets. Seven streptozotocin-induced diabetic rats each received 4.0-4.5 x 10(3) microencapsulated islets intraperitoneally. After transplantation, blood glucose dropped from 350 +/- 29 mg/dl to 142 +/- 12 mg/dl. To date, normoglycemia has been maintained for 222 days. Control animals either died or developed cataracts.

Animals↗
PubMedDate not supplied

In vitro culture and transplantation of encapsulated human fetal islets as an artificial endocrine pancreas.

There has been increasing evidence indicating that islet transplantation may offer an ideal endocrine replacement therapy for patients with Type I diabetes mellitus. However, allogenic islets are susceptible to immune rejection. In 1980, Lim and Sun first reported a novel technique of microencapsulation by which pancreatic islets used as transplants could be encapsulated and immunoisolated so as to survive and function for a period of 2-3 weeks. By further improving the biocompatibility of the capsular membrane, Sun's group demonstrated that islet allografts can be protected from rejection for up to 21 months in nonimmunosuppressed, streptozotocin-induced diabetic rats. The biocompatible polymer capsule membrane constitutes a physical barrier to the host's immune system. Permeability of the membrane can be controlled to allow free diffusion of small molecular nutrients, hormones, and metabolites, but exclude lymphocytes, leukocytes, and macromolecular immunoglobulins and complement. Darquy and Reach, in 1985, disclosed the role of the microcapsule membrane in protecting islets from cytotoxic antibodies. Sun's group further demonstrated that the microencapsulation technique effectively protected xenografts of rat islets transplanted into diabetic mice. In a previous report, we described the success of allotransplanted microencapsulated rat islets in treating streptozotocin-induced diabetes in Wistar rats. We now report the in vitro study of human fetal islets microencapsulated within an alginate-polylysine membrane. A preliminary clinical trial of allotransplants for the treatment of insulin-dependent diabetics is also presented.

Adult↗
PubMedDate not supplied

Migration of macrophage-like cells within encapsulated islets of Langerhans maintained in tissue culture.

Islets of Langerhans isolated from the pancreas and encapsulated in alginate-polylysine-alginate micro-spheres can potentially serve as a self-regulating supply of insulin in response to glucose loads. A longitudinal ultrastructural and immunohistochemical study of encapsulated rat islets cultured in CMRL-1969 media at a constant glucose concentration of 5.5 mmol/L (100 mg%) allowed several observations. First, acinar cells, which remain attached to isolated islets, disappeared within 1 wk in tissue culture. Damaged endocrine cells also disappeared at this time. Phagocytic cells having ultrastructural features suggesting that they are macrophages emerged from the islets within about a week and ingested portions of the inner layer of capsule polymer. These macrophage-like cells retained these polymers until their death which occurred at around 1-2 mo after isolation; at no time did we observe phagocytic cells actually breaching the microsphere capsules. Beta cells remained well-granulated over 90 days of culture but accumulated lipofuscin-like residual bodies. Under these conditions, these bodies began to accumulate appreciably after about one week in culture.

Animals↗
PubMedDate not supplied

In vitro and in vivo evaluation of microencapsulated porcine islets.

To provide a plentiful supply of pancreatic islets for future clinical transplants into diabetic patients, the authors have developed a simple and consistent method of isolation of porcine islets. Both in vitro and in vivo studies demonstrated that the islets were viable and functional. Xenotransplants of 1.5 x 10(3) - 2.5 x 10(3) of microencapsulated porcine islets into diabetic mice resulted in restoration of normoglycemia in 13 of 18 experimental animals for up to 10 months. A xenograft of 50 x 10(3) microencapsulated porcine islets into a spontaneously diabetic monkey normalized hyperglycemia for more than 150 days. This experiment indicated that the transplantation of encapsulated porcine islets has great potential as a clinical treatment in diabetes mellitus.

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