Slowed progression in models of Huntington disease by adipose stem cell transplantation.
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 treated 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 coactivator-1alpha (PGC-1alpha) 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-1alpha expression.


CONCLUSIONS
Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors.
Lee
Soon-Tae
ST
Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Chu
Kon
K
Jung
Keun-Hwa
KH
Im
Woo-Seok
WS
Park
Jeong-Eun
JE
Lim
Hun-Chang
HC
Won
Chong-Hyun
CH
Shin
Seung-Hyun
SH
Lee
Sang Kun
SK
Kim
Manho
M
Roh
Jae-Kyu
JK
D017667:Adipocytes / Q000637:transplantation*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D006816:Huntington Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D017378:Quinolinic Acid / Q000008:administration & dosage; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D033581:Stem Cell Transplantation / Q000379:methods
D017077:Culture Media, Conditioned; D017382:Reactive Oxygen Species; D017378:Quinolinic Acid