title: Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis.
abstract: Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1(G93A)). Treating symptomatic SOD1(G93A) mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1(G93A) mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1(G93A) mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1(G93A) mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1(G93A) mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS.
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Christine V
authors.initials: CV
authors.lastname: Fontanilla
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Huiying
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, P.R.C.
authors.forename: Qingpeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Timothy Z
authors.initials: TZ
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, P.R.C.
authors.forename: Changwei
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Johnstone
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.|Krannert Institute of Cardiology and the Indianapolis VA Center for regenerative medicine
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Pascuzzi
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Du
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D017354:Point Mutation; D013049:Spectrin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D013049:Spectrin; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases