New Exercise and Fitness Review
Hum Gene Ther. 2015 Mar 4;
Authors: Keswani SG, Balaji S, Katz AB, King A, Omar K, Habli M, Klanke C, Crombleholme TM
Abstract
Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intra-placental injection of adenoviral-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intra-placental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in early third trimester, brain sparing and a reduction in liver weight. Laparotomy was performed on New Zealand white rabbits at day 21 of 30 days gestation and litters were divided into 5 groups: Control(1st position)+PBS, Control+Ad-IGF-1, Runt(3rd position)+PBS, Runt+Ad-IGF-1, Runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal/fetal placenta interface (n=12) at 48 hours after gene therapy. There was very minimal gene transfer detected in the pups or maternal organs. At term, compared to the normally grown 1st position control, the runted third position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intra-placental Ad-IGF-1 gene therapy (p
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IGF - Intra-placental Gene Therapy with Ad-IGF-1 Corrects Naturally Occurring Rabbit
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