期刊
ANNALS OF NEUROLOGY
卷 66, 期 5, 页码 671-681出版社
WILEY
DOI: 10.1002/ana.21788
关键词
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资金
- Research Center for Rare Diseases [A080588]
- Korea Health 21 RD Project
- Ministry of Health Welfare [A080448]
- WCU-Neurocytomics [800-20080848]
- 21C Frontier Functional Proteomics [FPR08K1301-02210]
- Interdisciplinary Research Initiatives Program by College of Medicine
- Seoul National University
- Seoul National University Hospital Research Fund [03-2009-002]
Objective: Adipose-derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models. Methods. ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)-induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60-day-old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we created Mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media. Results: In the QA model, human ASCs reduced apomorphine-induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota-Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC-transplanted R6/2 mice expressed elevated levels of peroxisome proliferator-activated receptor gamma coactivacor-1 alpha (PGC-1 alpha) and reactive oxygen defense enzymes and showed activation of the Ak-t/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1 alpha expression. Interpretation: Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors.
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