Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Stem cell reports, 2018-01, Vol.10 (1), p.58-72

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. •hNSCs implanted in R6/2 HD mice improved motor and electrophysiological deficits•hNSCs are electrophysiologically active and are contacted by host nerve terminals•hNSCs improved motor and late-stage cognitive impairment in Q140 knockin mice•hNSCs reduced aberrant accumulation of mHTT protein and increased BDNF production 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.