Fetal pig islet-like cell clusters (ICCs) were transplanted into the thymus or omentum of STZ-induced diabetic pigs immunosuppressed with cyclosporine (CsA) and deoxyspergualin (DSG), as a potential treatment for type 1 diabetes. C-peptide levels in response to glucagon and arginine significantly increased over time using 1 litter of ICCs with highest levels obtained at 100 days post-transplantation. Increasing the number of ICCs to 2 litters was not advantageous. Histology of the graft showed all 4 pancreatic endocrine cells. Normoglycaemia was achieved for transient periods without insulin administration in 4 out of 12 pigs. These results suggest sub-optimal insulin production, possibly due to the adverse effects of CsA on the grafted β cells. The effect of CsA on adult porcine β cells was investigated and adverse effects were shown. Renal toxicity and adverse changes to the haematological parameters did not occur despite high CsA levels although minimal toxicity to the liver was observed. The results indicate that the use of CsA monotherapy in the maintenance phase to prevent rejection of allografted pancreatic β cells may become a subsequent problem over time. As an alternative to chronic immunossuppression, anti-CD3 monoclonal antibody was administered for 10 days in pigs. Using anti-CD3 alone, only 1 out 4 pigs showed cells positive for insulin. The addition of a 5-day CsA course administered the day before transplantation did not promote allograft survival. The use of DSG for 10 days with anti-CD3 promoted graft survival with the histology showing the 4 endocrine cells 3 weeks post-transplantation. An attempt was made to replace any form of immunossuppression by encapsulating fetal pig ICCs in barium alginate, which were able to remain viable when transplanted in NOD/SCID mice. Fibrosis was detected in BALB/c mice transplanted with encapsulated fetal ICCs suggesting that fetal pig ICCs shed antigens that elicit an immune response. Results from this study show that although fetal pig ICCs may be a viable source of insulin-producing cells, the use of CsA to prevent rejection has adverse effects on graft function. Encapsulation as well as transient immunosuppression is worthy of further investigation to prevent rejection of fetal pig ICCs.

Fetal pig islet-like cell clusters (ICCs) were transplanted into the thymus or omentum of STZ-induced diabetic pigs immunosuppressed with cyclosporine (CsA) and deoxyspergualin (DSG), as a potential treatment for type 1 diabetes. C-peptide levels in response to glucagon and arginine significantly increased over time using 1 litter of ICCs with highest levels obtained at 100 days post-transplantation. Increasing the number of ICCs to 2 litters was not advantageous. Histology of the graft showed all 4 pancreatic endocrine cells. Normoglycaemia was achieved for transient periods without insulin administration in 4 out of 12 pigs. These results suggest sub-optimal insulin production, possibly due to the adverse effects of CsA on the grafted β cells. The effect of CsA on adult porcine β cells was investigated and adverse effects were shown. Renal toxicity and adverse changes to the haematological parameters did not occur despite high CsA levels although minimal toxicity to the liver was observed. The results indicate that the use of CsA monotherapy in the maintenance phase to prevent rejection of allografted pancreatic β cells may become a subsequent problem over time. As an alternative to chronic immunossuppression, anti-CD3 monoclonal antibody was administered for 10 days in pigs. Using anti-CD3 alone, only 1 out 4 pigs showed cells positive for insulin. The addition of a 5-day CsA course administered the day before transplantation did not promote allograft survival. The use of DSG for 10 days with anti-CD3 promoted graft survival with the histology showing the 4 endocrine cells 3 weeks post-transplantation. An attempt was made to replace any form of immunossuppression by encapsulating fetal pig ICCs in barium alginate, which were able to remain viable when transplanted in NOD/SCID mice. Fibrosis was detected in BALB/c mice transplanted with encapsulated fetal ICCs suggesting that fetal pig ICCs shed antigens that elicit an immune response. Results from this study show that although fetal pig ICCs may be a viable source of insulin-producing cells, the use of CsA to prevent rejection has adverse effects on graft function. Encapsulation as well as transient immunosuppression is worthy of further investigation to prevent rejection of fetal pig ICCs.

Sugar intake is linked to developmental programming of obesity and diabetes. We hypothesized that supplementing ground beef in place of sugar during pregnancy would reduce fetal and offspring developmental programming. Gestating sows were fed 1 of 4 isocaloric supplements: control, ground beef, granulated sugar, or beef plus sugar. In the fetal study supplements were fed from d 40 to 110 of gestation and in the offspring study from d 40 until weaning. Gene expression differences in fetal liver and muscle were observed for IGF2 (P = 0.04), FBPase (P = 0.03), and IGF2R (P = 0.02). Differences were also seen in offspring back fat (sex by day interaction, P = 0.01), longissimus dorsi muscle area (treatment by sex, P = 0.001), body weight (sex, P = 0.0006; sex by day interaction, P < 0.0001), and plasma insulin concentrations (treatment by sex, P = 0.0002). / North Dakota Beef Commission / Topigs Norsvin / North Dakota. State Board of Agricultural Research and Education

Eighty-six crossbred (Duroc x Yorkshire) gilts were used in two trials (50 gilts in Trial 1 and 36 gilts in Trial 2) for an assessment of the effect of supplemental dietary fat during early gestation on fetal survival, fetal development, and fatty acid concentration in gilt plasma and fetal head and body. Three diets contained 4% (w/w) added fat either as coconut, soybean, or fish (menhaden) oils. A fourth diet was used as a control. On d 37 to 45 postbreeding, gilts were slaughtered and numerous fetal and ovarian measurements made. Two sets of four randomly selected fetuses per gilt from Trial 1 were prepared. Blood samples from each gilt were obtained on the day of slaughter for determination of the plasma fatty acid profile. Across both trials, percentage fetal survival did not differ according to treatment, but in Trial 2 fetal survival was higher (P < .06) for gilts fed fish oil, compared with the controls. The fatty acid profile of plasma of gilts and the conceptus tissues were similar; both were influenced by the fatty acid concentration of the diets. The ratio of n-3/n-6 fatty acids was higher in conceptus tissue than in maternal plasma and the ratio was higher (P < .05) for the fish oil diet compared with the other diets. The relatively high concentration of omega-3 fatty acids in fetal tissues supports the hypothesis that omega-3 fatty acids play a role in the development of the pig conceptus and contributes to improve fetal survival. However, the high percentage fetal survival observed in all the treatments may have masked benefits of supplemental oil. / Master of Science