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

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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768890/
https://www.ncbi.nlm.nih.gov/pubmed/29233555
http://dx.doi.org/10.1016/j.stemcr.2017.11.005
Descripción
Sumario: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.