Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis.
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.
Wei
X
X
Department of Neurology, School of Medicine, Indiana University, 975 W. Walnut St. IB457, Indianapolis, IN 46202, USA.
Zhao
L
L
Zhong
J
J
Gu
H
H
Feng
D
D
Johnstone
B H
BH
March
K L
KL
Farlow
M R
MR
Du
Y
Y
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000098:blood supply / Q000502:physiology*; D017077:Culture Media, Conditioned; D004789:Enzyme Activation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011188:Potassium / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism*
D053148:Caspase 3; D017077:Culture Media, Conditioned; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011188:Potassium; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat