S-T.L. and K.C. contributed equally to this work.
Slowed progression in models of huntington disease by adipose stem cell transplantation†
Article first published online: 29 JUN 2009
Copyright © 2009 American Neurological Association
Annals of Neurology
Volume 66, Issue 5, pages 671–681, November 2009
How to Cite
Lee, S.-T., Chu, K., Jung, K.-H., Im, W.-S., Park, J.-E., Lim, H.-C., Won, C.-H., Shin, S.-H., Lee, S. K., Kim, M. and Roh, J.-K. (2009), Slowed progression in models of huntington disease by adipose stem cell transplantation. Ann Neurol., 66: 671–681. doi: 10.1002/ana.21788
Potential conflict of interest: Nothing to report.
- Issue published online: 24 NOV 2009
- Article first published online: 29 JUN 2009
- Accepted manuscript online: 29 JUN 2009 12:00AM EST
- Manuscript Accepted: 12 JUN 2009
- Manuscript Revised: 8 JUN 2009
- Manuscript Received: 23 JUN 2008
- Research Center for Rare Diseases. Grant Number: A080588
- Korea Health 21 R&D Project, Ministry of Health & Welfare. Grant Numbers: A080448, 800-20080848
- 21C Frontier Functional Proteomics Project. Grant Number: FPR08K1301-02210
- Interdisciplinary Research Initiatives Program by College of Medicine, Seoul National University
- Seoul National University Hospital Research Fund. Grant Number: 03-2009-002
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.
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 treated mutant huntingtin gene-transfected cerebral neurons with ASC-conditioned media.
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 γ coactivator-1α (PGC-1α) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP-response element-binding proteins. ASC-conditioned media decreased the level of N-terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC-1α expression.
Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671–681