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A Mellgren

Publications and source records attributed to A Mellgren.

52 records · Page 3Linked to original sources

[Mother Kisa].

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Complementary Therapies↗

The renal subcapsular site offers better growth conditions for transplanted mouse pancreatic islet cells than the liver or spleen.

In order to investigate the importance of the transplantation site for the replication of grafted islet cells, we implanted syngeneic mouse pancreatic islets intrasplenically, intraportally and subcapsularly in the kidney. Fourteen days later the alloxan-diabetic mice were killed after an injection of tritiated thymidine, and the graft-bearing organs fixed and processed for autoradiography. The highest labelling indices were recorded for subcapsularly grafted islets, followed by intraportal and intrasplenic islets in that order. In separate experiments some islet-containing kidney sections were immune stained for insulin before the autoradiographic process. The labelling index of the insulin-positive cells was as high as in the entire islet cell population of the sections from the same mice stained with haematoxylin only. This indicates that the B cells of the islets replicate as often as the other islet cell types. The present data also suggest that the renal subcapsular space offers better growth conditions for transplanted islet cells than the liver or spleen.

Animals↗

Experimental studies of transplantation and regeneration of endocrine pancreatic cells.

Replacement of destroyed B-cells with new "healthy" ones appears to be the most physiological approach to treatment of insulin-dependent (type 1) diabetes. This could be achieved either by transplantation of isolated islets or pancreatic segments or by stimulation of the replicatory activity in the islet cells surviving the acute toxic or infectious insult. The results of our experimental investigations indicate that adult, mature insulin-producing cells can replicate very actively when challenged with a proper stimulus, such as when implanted into obese-hyperglycaemic mice. The growth of transplanted islets is, however, dependent on the site of implantation. Thus, the subcapsular space of the kidney is more favourable than the spleen. Furthermore, immunosuppressive therapy may impair islet cell replicatory activity, as demonstrated in this study for Cyclosporin A. In a search for factors stimulating islet cell replication, we found that the hepatotoxic agent galactosamine enhanced this process as observed autoradiographically one week after the injection. This fits in with previous case reports demonstrating increased mitotic activity in islets of patients suffering from various acute liver diseases. Altogether this series of experiments demonstrates that islet cell replication is a more dynamic process than has hitherto been believed. Obviously many conditions influence this process so significantly that an impact on the diabetic state of the patients can well be expected.

Animals↗

Tissue culture of human fetal pancreas. Development and function of B-cells in vitro and transplantation of explants to nude mice.

The present study evaluates the development and function of human fetal B-cells in vitro with a view to using such cells in future attempts for transplantation of human fetal pancreas to diabetic patients. A method previously described in our laboratory for preparing islets in vitro from the fetal rat pancreas has been applied and modified for use with human fetal pancreas. Pancreatic glands of different gestational ages were obtained from 37 consecutive prostaglandin-induced abortions. After a mild collagenase treatment, the partially disintegrated tissue was maintained in culture for 7 days in tissue culture medium RPMI 1640 plus 20% fetal calf serum to permit cell attachment and out-growth of endocrine cells. In 17 of the 37 consecutively cultured fetal pancreatic glands, islet-like cell clusters were formed. The 20 remaining glands were lost because of either bacterial contamination or lack of viability already before dissection had occurred. Sections of the newly formed cell clusters revealed well-preserved pancreatic cells showing frequent mitotic figures. The tissue exhibited a high rate of (pro)insulin biosynthesis and a modest insulin response to secretory stimuli, suggesting that the mechanism of glucose regulation by the fetal B-cells is not yet fully developed. Electron micrographs showed a large number of granule-containing cells, some of which were identified as B-cells. In nine cases, harvested cell clusters were implanted beneath the kidney capsule of nude mice. When these animals were killed after 2 mo, seven mice showed a considerable growth of the grafts with numerous islet-like structures containing insulin- and glucagon-positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗