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M S Cattral

Publications and source records attributed to M S Cattral.

At least 55 records · Page 3Linked to original sources
PubMed1993

The effect of cryopreservation on the survival and MHC antigen expression of murine islet allografts.

Cryopreservation is an effective method of islet storage that can facilitate clinical trials of islet transplantation. In the present study we examined the effect of cryopreservation on the survival of islet allografts and the quantity of islet MHC antigen expression. Islets isolated from CBA/J (H-2k) mice were transplanted into streptozotocin-induced diabetic BALB/c (H-2d) mice treated with or without antilymphocyte serum (ALS). Frozen/thawed (F/T) grafts were cooled slowly to -40 degrees C, stored at -196 degrees C, and thawed rapidly. Fresh and F/T isograft controls reversed diabetes promptly and maintained normoglycemia > 100 days. Allografts of fresh and F/T islets induced normoglycemia initially, but graft failure ensued at 18.2 +/- 1.5 and 16.4 +/- 1.9 days, respectively. ALS treatment prolonged allograft survival significantly to 35.3 +/- 3.9 and 37.5 +/- 6.3 days for fresh and F/T islets, respectively. Following cryopreservation, the quantity of class I antigen expression was reduced by 40%, while the quantity of class II expression was variable. These data indicate that murine islet MHC class I expression is reduced after cryopreservation. This decrease was not associated with altered survival of allogeneic grafts.

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PubMed1991

Transplantation of purified frozen/thawed canine pancreatic islet allografts with cyclosporine.

We studied the survival of defined volumes of highly purified frozen/thawed islets transplanted into the spleen of 4 groups of apancreatic mongrel dogs (total, 21), with or without cyclosporine from day -4 to day 30: group 1 (controls), without CsA, autograft of mean (+/- SE) islet volume 5 +/- 1 microliters/kg body weight; group 2, single-donor allograft, and group 3, multiple-donor allograft (both, 6 +/- 1 microliters/kg), both with CsA; and group 4, large-volume multiple-donor allograft (24 +/- 1 microliters/kg) with CsA. Grafts were cooled slowly to -40 degrees C, stored at -196 degrees C, and thawed rapidly. The CsA dose was adjusted to maintain whole-blood trough values of 600-800 micrograms/L, and allograft recipients manifesting early hyperglycemia were given insulin to maintain plasma glucose concentration below 150 mg/dl. In group 1, two dogs died early (graft failure in 1, intussusception in 1), but the remaining five were normoglycemic at 30 days. In groups 2 and 3, hyperglycemia ensued from about day 2.5, but 4 of 5 grafts in group 2 and all grafts in group 3 secreted insulin into the splenic vein at 30 days. In group 4, normoglycemia ensued within 24 hr of transplantation and was maintained in all 6 dogs for 30 days; the grafts failed 15 +/- 2 days after CsA was stopped. The data demonstrate prolonged function of purified frozen/thawed islets after transplantation into these outbred dogs but indicate a need for a greater volume of allogeneic islets from multiple donors than of autologous islets to achieve normoglycemia.

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PubMed1990

Critical mass of islets that function after implantation in a large mammalian.

A major problem that limits clinical islet transplantation is insufficient information on the critical quantity of islets needed to reverse insulin dependence. To address this problem, we have previously identified the critical number of purified islets of known size that consistently induced normoglycemia in a large mammal model of type I diabetes. In the present studies, we found that the dose-response relationship between the volume of islets transplanted and consistent normoglycemia in dogs corresponded to greater than 4.1 microliters islet tissue per kilogram body weight. The functional outcome of similar quantities of purified islets was then examined after autoimplantation into splenic or hepatic sites and after splenic implantation by venous reflux or pulp injection. During prolonged follow-up, four of five initially normoglycemic recipients of intrahepatic islets became hyperglycemic within 1 year and the other failed at 26 months. In contrast, function of intrasplenic islets was more durable with delayed onset of hyperglycemia observed in only two of six grafts at 13 and 18 months. Sustained normoglycemia was induced by splenic venous reflux of islets in six of seven dogs, but intrapulp injection succeeded in only two of six. Islet allografts implanted to the spleen (n = 10) or to the kidney capsule (n = 6) of Cyclosporine-treated recipients induced normoglycemia in all, but sustained function ensued in only the intrasplenic group when the islet mass was augmented by 40%. These data define the critical islet volume needed to induce normoglycemia in a large mammal. Islets implanted by venous reflux to spleen provide more durable long-term function than the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1989

Transplantation of purified single-donor canine islet allografts with cyclosporine.

We evaluated the survival of highly purified freshly isolated pancreatic islets transplanted from single canine donors into 20 outbred mongrel dogs immunosuppressed with cyclosporine or untreated. The grafts (mean weight +/- SE, 0.5 +/- 0.1 g, containing 122 +/- 8 X 10(3) islets; purity 91% by electron microscopy) were transplanted into 3 groups of dogs: group 1, autograft without CsA (5444 +/- 688 islets/kg body weight, n = 6); group 2, allograft without CsA (6669 +/- 1744, n = 4); and group 3, allograft with CsA (8645 +/- 1149, n = 10). The CsA was injected i.m. daily for 4 days before and 30 days after transplantation. Fasting plasma glucose (PG, mg/dl) and serum CsA trough values were determined daily. Intravenous glucose tolerance tests were done before and after transplantation, for calculation of K values (decline in glucose, %/min; preoperatively, mean K = 3.9 +/- 0.2). In group 1 all 6 dogs were normoglycemic (PG = 98 +/- 2 and K = 1.8 +/- 0.2) at 1 month; in group 2 the graft failed in all 4 dogs, at 4 +/- 1.2 days; in group 3 all 10 dogs were normoglycemic initially. Of the group 3 dogs, 4 died (intussusception developed in 2, and the graft failed at 3 and 9 days in 2 the CsA values of which were less than 300 micrograms/L preoperatively), but the other 6 were still normoglycemic when the CsA was stopped at 30 days (mean PG = 132 +/- 16 and K = 0.9 +/- 0.2; P less than 0.05 vs. group 1). Their CsA values were 708 +/- 197 before and 359 +/- 41 micrograms/L during the third week after transplantation; their grafts failed 12.3 +/- 3.4 days after the cessation of CsA. This data is unique in demonstrating prolonged function of purified allogeneic islets transplanted from individual outbred canine donors, but glucose tolerance was impaired. CsA at serum levels greater than 300 micrograms/L induced prolonged survival of purified canine islets and rejection was prompt when it was stopped.

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PubMed1988

Normoglycemia after implantation of purified islet cells in dogs.

A major problem that limits the effectiveness of clinical trials of islet transplantation is the inability to isolate sufficient pure viable islets from a single pancreas. The authors have evaluated this problem, using dogs rendered diabetic by total pancreatectomy. An average of 123 +/- 11 X 10(3) highly purified islets (mean graft weight 0.75 +/- 0.1 g) were implanted as splenic allografts (seven dogs), splenic autografts (six dogs) or liver autografts (six). In the autograft recipients, fasting normoglycemia was maintained during follow-up to 10 months; onset of hyperglycemia was delayed in three liver recipients and one splenic autograft recipient at 1.5, 2, 8 and 10 months respectively. The K values (decline in glucose levels in %/min) during intravenous glucose tolerance testing were more than 1.0. Six recipients of allografts and cyclosporine (CsA) were normoglycemic when CsA trough serum levels were greater than 300 micrograms/L, although the fasting plasma glucose level was higher than that in autograft recipients. These data show that purified islets isolated from a large mammal will maintain fasting normoglycemia for prolonged periods after auto- or alloimplantation.

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