title: Extracts of adipose derived stem cells slows progression in the R6/2 model of Huntington's disease.
abstract: Stem cell therapy is a promising treatment for incurable disorders including Huntington's disease (HD). Adipose-derived stem cell (ASC) is an easily available source of stem cells. Since ASCs can be differentiated into nervous stem cells, it has clinically feasible potential for neurodegenerative disease. In addition, ASCs secrete various anti-apoptotic growth factors, which improve the symptoms of disease from transplanted ASCs. Thus, cell-free extracts of ASCs (ASCs-E) could be a potential candidate for treatment of HD. Here, we investigated effects of ASCs-E on R6/2 HD mouse model and neuronal cells. In R6/2 HD model, injection of ASCs-E improved the performance in Rotarod test. ASCs-E also ameliorated striatal atrophy and mutant huntingtin aggregation in the striatum. In Western blot increased expressions of p-Akt, p-CREB and PGC1α were noted by injection of ASCs-E, when comparing to the R6/2 HD model. Neuro2A neuroblastoma cells treated with ASCs-E showed increased expression of p-CREB and PGC1α. In conclusion, ASCs-E delayed disease progression in animal model of HD by restoring of CREB-PGC1α pathway and could be a potential resource for treatment of HD.
authors.affiliation: Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Im
authors.forename: Jaejun
authors.initials: J
authors.lastname: Ban
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Lim
authors.forename: Mijung
authors.initials: M
authors.lastname: Lee
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001284:Atrophy; D001522:Behavior, Animal / Q000187:drug effects; D002457:Cell Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002457:Cell Extracts; D017362:Cyclic AMP Response Element-Binding Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2041-6
references.pmid: 12576549
references.citation: Hum Mol Genet. 2010 Aug 15;19(16):3190-205
references.pmid: 20529956
references.citation: Drugs. 2010 Mar 26;70(5):561-71
references.pmid: 20329804
references.citation: Biochem Biophys Res Commun. 2012 Oct 5;426(4):475-9
references.pmid: 22960177
references.citation: Int Clin Psychopharmacol. 2004 Mar;19(2):51-62
references.pmid: 15076012
references.citation: J Neurosci. 2009 Sep 16;29(37):11550-9
references.pmid: 19759302
references.citation: Nat Rev Neurosci. 2006 May;7(5):395-406
references.pmid: 16760919
references.citation: J Clin Invest. 2011 Feb;121(2):476-83
references.pmid: 21285520
references.citation: Stem Cells. 2007 Apr;25(4):818-27
references.pmid: 17420225
references.citation: J Comp Neurol. 2002 Jul 29;449(3):241-69
references.pmid: 12115678
references.citation: Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2542-7
references.pmid: 16224047
references.citation: Epilepsia. 2011 Sep;52(9):1617-26
references.pmid: 21777228
references.citation: EMBO Rep. 2004 Oct;5(10):958-63
references.pmid: 15459747
references.citation: Cell. 2006 Oct 20;127(2):397-408
references.pmid: 17055439
references.citation: Curr Opin Lipidol. 2007 Dec;18(6):645-9
references.pmid: 17993810
references.citation: Cell. 2006 Nov 3;127(3):465-8
references.pmid: 17081970
references.citation: Lancet. 2007 Jan 20;369(9557):218-28
references.pmid: 17240289
references.citation: Eur J Neurosci. 2005 Mar;21(6):1478-88
references.pmid: 15845076
references.citation: Stem Cells. 2011 Jun;29(6):913-9
references.pmid: 21506195
references.citation: Ann Neurol. 2000 Jan;47(1):80-6
references.pmid: 10632104
references.citation: Cell. 1996 Nov 1;87(3):493-506
references.pmid: 8898202
references.citation: Circulation. 2010 Aug 3;122(5):517-26
references.pmid: 20679581
references.citation: Neurobiol Dis. 2013 Jun;54:414-20
references.pmid: 23376682
references.citation: Nat Med. 2009 Dec;15(12):1407-13
references.pmid: 19915593
references.citation: Circulation. 2004 Mar 16;109(10):1292-8
references.pmid: 14993122
references.citation: Dev Cell. 2002 Jun;2(6):831-7
references.pmid: 12062094
references.citation: Mol Biol Cell. 2002 Dec;13(12):4279-95
references.pmid: 12475952
references.citation: Ann Neurol. 2009 Nov;66(5):671-81
references.pmid: 19938161
references.citation: J Invest Dermatol. 2011 Jul;131(7):1559-67
references.pmid: 21451545
references.citation: J Cereb Blood Flow Metab. 2000 Oct;20(10):1393-408
references.pmid: 11043902
references.citation: Mol Ther. 2009 Jun;17(6):939-46
references.pmid: 19337235
references.citation: Circ Res. 2008 Nov 21;103(11):1204-19
references.pmid: 19028920
references.citation: Curr Opin Mol Ther. 2010 Aug;12(4):442-9
references.pmid: 20677095
references.citation: Cell. 2006 Oct 6;127(1):59-69
references.pmid: 17018277