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Inducible Expression of GDNF in Transplanted iPSC-Derived Neural Progenitor Cells.
Akhtar, Aslam Abbasi; Gowing, Genevieve; Kobritz, Naomi; Savinoff, Steve E; Garcia, Leslie; Saxon, David; Cho, Noell; Kim, Gibum; Tom, Colton M; Park, Hannah; Lawless, George; Shelley, Brandon C; Mattis, Virginia B; Breunig, Joshua J; Svendsen, Clive N.
Afiliação
  • Akhtar AA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Gowing G; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Kobritz N; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Savinoff SE; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Garcia L; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Saxon D; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Cho N; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Kim G; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Tom CM; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Park H; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Lawless G; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Shelley BC; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Mattis VB; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Breunig JJ; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, U
  • Svendsen CN; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: clive.svendsen@cshs.org.
Stem Cell Reports ; 10(6): 1696-1704, 2018 06 05.
Article em En | MEDLINE | ID: mdl-29706501
ABSTRACT
Trophic factor delivery to the brain using stem cell-derived neural progenitors is a powerful way to bypass the blood-brain barrier. Protection of diseased neurons using this technology is a promising therapy for neurodegenerative diseases. Glial cell line-derived neurotrophic factor (GDNF) has provided benefits to Parkinsonian patients and is being used in a clinical trial for amyotrophic lateral sclerosis. However, chronic trophic factor delivery prohibits dose adjustment or cessation if side effects develop. To address this, we engineered a doxycycline-regulated vector, allowing inducible and reversible expression of a therapeutic molecule. Human induced pluripotent stem cell (iPSC)-derived neural progenitors were stably transfected with the vector and transplanted into the adult mouse brain. Doxycycline can penetrate the graft, with addition and withdrawal providing inducible and reversible GDNF expression in vivo, over multiple cycles. Our findings provide proof of concept for combining gene and stem cell therapy for effective modulation of ectopic protein expression in transplanted cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica no Desenvolvimento / Transplante de Células-Tronco / Fator Neurotrófico Derivado de Linhagem de Célula Glial / Células-Tronco Pluripotentes Induzidas / Células-Tronco Neurais Idioma: En Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica no Desenvolvimento / Transplante de Células-Tronco / Fator Neurotrófico Derivado de Linhagem de Célula Glial / Células-Tronco Pluripotentes Induzidas / Células-Tronco Neurais Idioma: En Ano de publicação: 2018 Tipo de documento: Article