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.
Interpretation: Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors.