IFATS Collection: The Conditioned Media of Adipose Stromal Cells Protect Against Hypoxia-Ischemia-Induced Brain Damage in Neonatal Rats

Abstract

Abstract Adipose tissue stroma contains a population of mesenchymal stem cells, which support repair when administered to damaged tissues, in large part through secreted trophic factors. We directly tested the ability of media collected from cultured adipose-derived stem cells (ASCs) to protect neurons in a rat model of brain hypoxic-ischemic (HI) injury. Concentrated conditioned medium from cultured rat ASCs (ASC-CM) or control medium was infused through the jugular vein of neonatal Sprague-Dawley rats subjected to HI injury. The ASC-CM was administered either 1 hour before or 24 hours after induction of injury. Analysis at 1 week indicated that administration at both time points significantly protected against hippocampal and cortical volume loss. Analysis of parallel groups for behavioral and learning changes at 2 months postischemia demonstrated that both treated groups performed significantly better than the controls in Morris water maze functional tests. Subsequent post-mortem evaluation of brain damage at the 2-month time point confirmed neuronal loss to be similar to that observed at 1 week for all groups. We have identified several neurotrophic factors in ASC-CM, particularly insulin-like growth factor-1 and brain-derived neurotrophic factor, which are important factors that could contribute to the protective effects of ASCs observed in studies with both in vitro and in vivo neuronal injury models. These data suggest that delivery of the milieu of factors secreted by ASCs may be a viable therapeutic option for treatment of HI, as well as other brain injuries.