Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis

• Published in: Neuroscience letters 2009-10, Vol.462 (1), p.76-79
• Main Authors: Wei, X., Zhao, L., Zhong, J., Gu, H., Feng, D., Johnstone, B.H., March, K.L., Farlow, M.R., Du, Y.
• Format: Article
• Language: English
• Subjects: Adipose stromal cells; Adipose Tissue - secretion; Animals; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Caspase 3 - metabolism; Caspase-3; Cell Survival - physiology; Cells, Cultured; Cerebella granule neuron; Cerebellum - blood supply; Cerebellum - physiology; Culture Media, Conditioned; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Insulin-Like Growth Factor I - metabolism; Neurons - physiology; Neuroprotection; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Potassium - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Inbred Lew; Signal Transduction; Stromal Cells - secretion; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.06.054

Transplantation of pluripotent adipose stem/stromal cells (ASC) alleviates tissue damage and improves functional deficits in both stroke and cardiovascular disease animal models. Recent studies indicate that the primary mechanism of ASC-induced repair may not be directly related to tissue regeneration through differentiation, but rather through paracrine mechanisms provided by secreted pro-survival and repair-inducing trophic factors. In this study, we have found that ASC-conditioned medium (ASC-CM) potently protected cerebellar granule neurons (CGN) from apoptosis induced by serum and potassium deprivation. Neural cell protection was mostly attributable to activated caspase-3 and Akt-mediated neuroprotective pathway signaling. Specific neutralization of neurotrophic factor activity demonstrated that serum and potassium deprivation-induced Akt-mediated neuroprotection and caspase-3-dependent apoptosis were mainly modulated by IGF-1. These data suggest that of the many neuroprotective factors secreted by ASC, IGF-1 is the major factor that mediates protection against serum and potassium deprivation-induced CGN apoptosis. This study establishes a mechanistic basis supporting the therapeutic application of ASC for neurological disorders, specifically through paracrine support provided by trophic factor secretion.