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Open Access Publications from the University of California

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

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

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.

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