Related Experiment Video
Updated: Feb 26, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Recombinant human insulin-like growth factor 1 complex preserves lung development in mechanically ventilated preterm
Kurt H Albertine1, Andrew Rebentisch1, Elaine Dawson1
1Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, UT, United States.
Rationale:
Bronchopulmonary dysplasia is associated with low concentrations of insulin-like growth factor 1 (IGF-1) protein in preterm infants. Postnatal replenishment of IGF-1 protein is a potential approach to prevent the decline in preterm human infants. Our recent 3-day pilot study in mechanically ventilated preterm lambs (131 days' gestation; n = 6) demonstrated downstream signaling of human IGF-1 in sheep cells in vitro and that 1.5 mg/kg/d of recombinant human (rh) IGF-1 bound to binding protein 3 (IGFBP3; rhIGF-1 complex) delivered by continuous intravenous infusion provided physiological replacement of IGF-1 protein in plasma and suggested better pulmonary outcomes.
Objective:
This study assessed a longer period (7 days) of continuous treatment and larger sample size (10/group), using younger mechanically ventilated preterm lambs (128 days' gestation; equivalent to human lung development at ∼28 weeks' gestation) to allow evidence of preservation of respiratory gas exchange, alveolar formation and capillary growth, lung mechanics, and terminal bronchiole smooth muscle abundance.
Methods:
Preterm lambs were mechanically ventilated for 7 days. Lambs were randomized to blinded treatment with continuous intravenous infusion of either saline (vehicle control; 5 female/5 male) or rhIGF-1 complex (5 female/5 male), starting at 6 hours after operative delivery.
Measurements And Main Results:
RhIGF-1 complex significantly improved indices of respiratory gas exchange, alveolar formation, alveolar capillary growth, and VEGF-R2 messenger RNA expression, without adverse effects on liver or kidney function.
Conclusions:
RhIGF-1 complex may be an effective and safe therapy to promote functional and structural development underlying lung maturation in preterm infants and reduce the risk of developing bronchopulmonary dysplasia.
