Transplantation Of Fetal Pancreas Research Articles

Permeability of the 17-day fetal rat pancreas to glycerol and dimethylsulfoxide

Experimentally induced diabetes in rats can be reversed by the transplantation of several fresh or frozen-thawed fetal pancreases. An important question to both the mechanistic and practical aspects of cryobiology is the role played by the permeation of protective additives during freezing, thawing, and subsequent dilution. Answers require knowledge of the kinetics of permeation of the specific additive into the cell or tissue. In this paper, we report isotopic measurements of the rate of permeation of 2 M glycerol and 1 and 2 M dimethylsulfoxide (Me 2SO) into 17-day fetal pancreases at 0 and 22 °C. In Me 2SO, equilibrium was achieved in about 10–15 min at 0 °C and in less than 10 min at 22 °C. In glycerol, equilibrium was attained in about 60 min at 22 °C; but at 0 °C permeation was only 65% complete after 180 min. In general, Me 2SO permeated 10–30 times more rapidly than glycerol at 0 °C, and glycerol permeated about 10 times more rapidly at 22 than at 0 °C. The kinetics of permeation were more characteristic of a two-compartment than a single-compartment system. In all probability, the two compartments are the intercellular space and the intracellular space. The permeability data suggest that each compartment occupies about half the total volume.

Islet cells grow after transplantation of fetal pancreas and control of diabetes.

The capacity of a fetal rat pancreas to grow and function was assessed after its transplantation into adult diabetic rats. One month after induction of diabetes by streptozotocin (SZ) (72.5 mg/kg) in adult Lewis rats, one syngeneic 17-17½ day fetal pancreas was transplanted under the kidney capsule. Insulin, initially 3 U/day and decreasing to 0.5 U every other day, was given for 27.5 ± 1.7 (× ± SEM) days (total dose, 48 ± 4 U) until the diabetes reversed (45 ± 3 days). Plasma glucose, 481 ± 10 mg/dl after SZ, fell after transplantation and cessation of insulin injections during a 4-mo period to 129 ± 2 mg/dl. Urine volume fell from 82 ± 4 ml per day to normal (12 ± 2), and glucose excretion, which was 7.7 ± 0.4 g per day after SZ, completely disappeared from the urine. The disappearance rate of glucose injected into the circulation, which was 0.50 ± 0.07% per minute in untreated diabetes, reverted to normal, 2.78 ± 0.18% per minute, not different from that in the normal control, 2.55 ± 0.13% per minute. Plasma insulin in control diabetic rats was totally unresponsive to glucose injection, despite a rise in plasma glucose concentration from 471 ± 5 mg/dl to 621 ±18 mg/dl. In transplanted rats, plasma insulin was moderately higher than normal before and at most time points after glucose injection. After removal of the transplanted pancreases, plasma glucose, urine volume, and glucose excretion returned to pretransplant levels and ketones appeared in the urine of all rats. Analysis of the insulin content of the pancreases removed 77 to 279 days after transplantation gave a value of 818 ± 43 mil, which is 22% of the insulin content of normal rats. To achieve optimal growth and function of a transplanted fetal pancreas, careful control of the blood glucose is necessary during the period of growth and development.

Syngeneic Transplantation of Fetal Rat Pancreas: III. Effect of Insulin Treatment on the Growth and Differentiation of the Pancreatic Implants After Reversal of Diabetes

Eight 18-316 fetal pancreases were transplanted to syngeneic alloxan diabetic male rats. Some of the recipients were treated with insulin for a 7-day period immediately after transplant. By previously published clinical criteria, three groups of recipients could be identified after reversal of diabetes by the transplanted tissue: insulin-treated rapid reversal; insulin-treated slow reversal; and control (not treated with insulin). Five animals in each group were sacrificed after glucose tolerance testing for morphologic and hormonal analysis of the transplanted tissue. The insulin-,glucagon-, and somatostatin-positive islet cell masses of the fetal pancreatic implants were quantitated. There was a correlation between the beta cell mass of the implants and the glucose tolerance exhibited by the host animals. The rapid response insulin-treated recipients had significantly greater implant beta cell mass and insulin content compared with the other groups. There was no difference in implant alpha cell mass among the groups, but the insulin-treated implants had a significantly greater glucagon content. The delta cell mass of insulin-treated rapid response was less than that of the other two groups. The results are discussed in relation to previously reported morphometric analysis 15 days after transplantation. The relationships of transplanted beta cell mass, beta cell differentiation, transplant site, and cell-to-cell interactions within the transplanted islet to the control of glucose homeostasis are also discussed.

Syngeneic transplantation of fetal rat pancreas. III. Effect of insulin treatment on the growth and differentiation of the pancreatic implants after reversal of diabetes

Syngeneic transplantation of fetal rat pancreas. III. Effect of insulin treatment on the growth and differentiation of the pancreatic implants after reversal of diabetes

Syngeneic transplantation of fetal rat pancreas. II. Effect of insulin treatment on the growth and differentiation of pancreatic implants fifteen days after transplantation

Syngeneic transplantation of fetal rat pancreas. II. Effect of insulin treatment on the growth and differentiation of pancreatic implants fifteen days after transplantation

Syngeneic Transplantation of Fetal Rat Pancreas: II. Effect of Insulin Treatment on the Growth and Differentiation of Pancreatic Implants Fifteen Days After Transplantation

Eight 18-days-postcoitum fetal pancreases were transplanted to isogenic alloxan-diabetic male rats. Some recipients were treated with insulin for seven days immediately after transplantation. Eight animals in both the insulin-treated group and control group were killed 15days after transplantation for morphologic and hormonal studies of the transplanted tissue. Using the morphometric technique of linear scanning, the insulin, glucagon, and somatostatin immunocytochemically positive, cell masses of the fetal pancreatic implants were quantitated. The beta cell mass of the implants from the control animals increased roughly eightfold from the time of transplant; insulin treatment resulted in a further two- to threefold increase. The insulin content of the implants increased more than did the beta cell mass, resulting in the fivefold increase in insulin per beta cell. The alpha cell and delta cell masses did not change during the transplant site, the mass of functional beta cells, and the cell-to-cell content of the implanted tissue. These results are discussed in relation to previous quantitative studies of pancreatic islet cell growth. The relationships of the transplant site, the mass of functional beta cell, and the cell-to-cell interaction within the islet to the maintenance of glucose homeostasis are also discussed.

Feeding and metabolic patterns in rats with truncular vagotomy or with transplanted beta-cells.

The night- and daytime basal plasma insulin levels and insulin responses to an intravenous glucose load, basal blood glucose levels and rates of glucose uptake, and, finally, the diurnal patterns of blood glucose levels were investigated in normal compared to vagotomized Wistar rats. The same comparisons were made between normal and diabetic Lewis rats recovered after fetal pancreas transplantation in the kidney capsule. In an attempt to clarify the relationship between the metabolic and feeding diurnal patterns, a detailed study of the meal pattern of vagotomized and transplanted rats was performed. It was shown that 1) a truncular vagotomy abolished both the metabolic and feeding diurnal cyclicity; 2) both the metabolic and feeding diurnal rhythms were maintained in case of a selective denervation beta-cells. The relationship between the metabolic and feeding diurnal rhythms and the role of the vagus nerve are discussed.

Fetal pancreas transplantation for reversal of streptozotocin-induced diabetes in rats.

Streptozotocin-induced diabetes in rats was completely reversed by transplantation of syngeneic fetal pancreases placed beneath the kidney capsule. To accomplish complete reversal of diabetes, four or more pancreases were necessary; three resulted in partial reversal, and two produced a slight but significant effect in some recipients. Removal of the transplants resulted in the prompt return of diabetes. The islets of Langerhans in the transplants functioned homeostatically; this was indicated by regular normal blood glucose values, in addition to normal findings in blood IRI response and glucose disappearance rate after glucose injection. Disappearance of exocrine elements, with only ducts and fibrous tissue remaining, resulted in a pure endocrine organ. The advantages of this technie, such as ease of accessibility for placement, observation, and removal, are of great importance for possible application to humans.

Fetal pancreas transplantation for reversal of streptozotocin-induced diabetes in rats

Fetal pancreas transplantation for reversal of streptozotocin-induced diabetes in rats

Control of experimental diabetes mellitus in rats by transplantation of fetal pancreases.

Experimental diabetes mellitus in young adult Lewis rats was successfully treated by transplantation of fetal pancreases from syngeneic fetuses. Complete or partial control lasting up to 165 days was achieved in 64 percent of recipients by using two to three pancreases of fetal age (15 to 18(1/2) days) placed under each kidney capsule. Islets of Langerhans without exocrine elements were present in the transplants.