Human adipose-derived stem cells enhance the glutamate uptake function of GLT1 in SOD1(G93A)-bearing astrocytes.
Impaired glutamate uptake function of astrocytes associated with accumulation of extracellular glutamate is a well-documented feature of amyotrophic lateral sclerosis (ALS). Enhancing the uptake function of astrocytic glutamate transport 1 (GLT1) may be a potential treatment for this disease. Human adipose-derived stem cells (hADSCs) are capable of secreting a large number of cytokines which exhibit diverse pharmacological effects. Therefore, we investigate the influence of the soluble factors released by hADSCs on the GLT1 in primary astrocytes cultured from SOD1(G93A) mice, a widely studied mutant human SOD1 transgenic model of ALS. Our data indicate that soluble factors from hADSCs significantly upregulate the expression of GLT1 in SOD1(G93A)-bearing astrocytes, which result in enhanced glutamate uptake function. The upregulation of GLT1 is accompanied by the inhibition of caspase-3 activation in mutant astrocytes. In addition, we find that hADSCs cocultured with SOD1(G93A)-bearing astrocytes produce more VEGF, HGF and IGF-1, which are reported to have neuroprotective effects. Our results suggest that hADSCs may be a potential candidate in cellular therapy for ALS.
Gu
Ran
R
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
Hou
Xiaomei
X
Pang
Rongqing
R
Li
Ling
L
Chen
Fei
F
Geng
Jia
J
Xu
Yongfeng
Y
Zhang
Cheng
C
D000273:Adipose Tissue / Q000166:cytology*; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D018920:Coculture Techniques; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis*; D018698:Glutamic Acid / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D061945:Caspase Inhibitors; D027342:Excitatory Amino Acid Transporter 2; C000606290:SOD1 protein, human; D042461:Vascular Endothelial Growth Factor A; D018698:Glutamic Acid; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1