Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

Jack C. Reidling, Aroa Relaño-Ginés, Sandra M. Holley, Joseph Ochaba, Cindy Moore, Brian Fury, Alice Lau, Andrew H. Tran, Sylvia Yeung, Delaram Salamati, Chunni Zhu, Asa Hatami, Carlos Cepeda, Joshua A. Barry, Talia Kamdjou, Alvin King, Dane Coleal-Bergum, Nicholas R. Franich, Frank M. LaFerla, Joan S. SteffanMathew Blurton-Jones, Charles K. Meshul, Gerhard Bauer, Michael S. Levine, Marie Francoise Chesselet, Leslie M. Thompson

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Huntington's disease (HD) is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT) gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP)-grade human embryonic stem cell-derived neural stem cell (hNSC) line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF) in both models. These findings hold promise for future development of stem cell-based therapies. Human GMP-grade neural stem cell transplantation rescues behavioral deficits and electrophysiological alterations in Huntington's disease mice, and rescue is associated with reduced accumulation of mutant Huntingtin protein.

Original languageEnglish (US)
Pages (from-to)58-72
Number of pages15
JournalStem Cell Reports
Issue number1
StatePublished - Jan 1 2018


  • embryonic stem cells
  • Huntington's disease
  • neural stem cell
  • Q140 mice
  • R6/2 mice
  • transplantation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


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