Inducible Expression of GDNF in Transplanted iPSC-Derived Neural Progenitor Cells

• DOI: 10.1016/j.stemcr.2018.03.024
• Publication Date: 2018-04-26T15:41:14Z
• Authors: Aslam Abbasi Akhtar; Genevieve Gowing; Naomi Kobritz; Steve E. Savinoff; Leslie Garcia; David Saxon; Noell Cho; Gibum Kim; Colton M. Tom; Hannah Park; George Lawless; Brandon C. Shelley; Virginia B. Mattis; Joshua J. Breunig; Clive N. Svendsen
• Keywords: 0301 basic medicine; Genetic Vectors; Induced Pluripotent Stem Cells; Cell- and Tissue-Based Therapy; Gene Expression; Gene Expression Regulation, Developmental; Genetic Therapy; Plants, Genetically Modified; 3. Good health; 03 medical and health sciences; Neural Stem Cells; Genes, Reporter; Transduction, Genetic; Report; Humans; Glial Cell Line-Derived Neurotrophic Factor; Transgenes; Stem Cell Transplantation

Trophic factor delivery to the brain using stem cell-derived neural progenitors is a powerful way bypass blood-brain barrier. Protection of diseased neurons this technology promising therapy for neurodegenerative diseases. Glial cell line-derived neurotrophic (GDNF) has provided benefits Parkinsonian patients and being used in clinical trial amyotrophic lateral sclerosis. However, chronic trophic prohibits dose adjustment or cessation if side effects develop. To address this, we engineered doxycycline-regulated vector, allowing inducible reversible expression therapeutic molecule. Human induced pluripotent (iPSC)-derived were stably transfected with vector transplanted into adult mouse brain. Doxycycline can penetrate graft, addition withdrawal providing GDNF vivo, over multiple cycles. Our findings provide proof concept combining gene effective modulation ectopic protein cells.