Get access

Slowed progression in models of huntington disease by adipose stem cell transplantation

Authors

  • Soon-Tae Lee MD,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
    Search for more papers by this author
    • S-T.L. and K.C. contributed equally to this work.

  • Kon Chu MD, PhD,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
    Search for more papers by this author
    • S-T.L. and K.C. contributed equally to this work.

  • Keun-Hwa Jung MD, PhD,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
    Search for more papers by this author
  • Woo-Seok Im MS,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    Search for more papers by this author
  • Jeong-Eun Park MS,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    Search for more papers by this author
  • Hun-Chang Lim MS,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    Search for more papers by this author
  • Chong-Hyun Won MD,

    1. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Seung-Hyun Shin MS,

    1. Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
    Search for more papers by this author
  • Sang Kun Lee MD, PhD,

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
    Search for more papers by this author
  • Manho Kim MD, PhD,

    Corresponding author
    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
    • Department of Neurology, Seoul National University Hospital, 101, Daehangno, Jongno-Gu, Seoul, 110-744, South Korea
    Search for more papers by this author
  • Jae-Kyu Roh MD, PhD

    1. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
    2. Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, South Korea
    Search for more papers by this author

  • Potential conflict of interest: Nothing to report.

Abstract

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 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.

Interpretation

Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671–681

Ancillary