AUGMENTOR OF LIVER-REGENERATION ENHANCES THE SUCCESS RATE OF FETAL PANCREAS TRANSPLANTATION IN RODENTS

Background. Treatment of fetal pancreas (FP) isografts with insulin-li ke growth factor-I greatly improves the rate of conversion to euglycem ia in diabetic rats. Complete knowledge of other factors that may faci litate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers, ALR has trophic effects o n regenerating Liver. We studied the effects of in situ administration of this agent on FP isografts in rats, Methods. Streptozotocin-diabet ic Lewis rats (blood glucose >300 mg/dl) received 16 FP isografts tran splanted intramuscularly, ALR was delivered hom day 1 through day 14, in doses of 40 or 400 ng/kg/d, Animals were followed for 3 months with serial weights and blood glucose monitoring, These animals were compa red with those treated with vehicle alone. Results. Of the group treat ed with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) were eugl ycemic (P = 0.0003), Of the group treated with ALR at 400 ng/kg/day fo r 14 days, 88% (seven of eight) were euglycemic (P = 0.0007), Of the g roup treated with vehicle alone, none of the six were euglycemic. Eugl ycemia is defined here as glucose < 200 mg/dl for 3 days. Pathology of the intramuscular transplant site showed patches of islet tissue embe dded in fat. These patches demonstrated insulin immunoreactivity. Conc lusions. Diabetes was reversed in a significantly greater proportion o f FP + ALR-treated recipients than those animals treated with vehicle alone. Local delivery of growth factors may be used as an adjunct to F P transplantation to improve the rate of success. This in situ model m ay be useful to further evaluate other soluble factors.