• M.T. Dell'Anno
  • M. Caiazzo
  • D. Leo
  • E. Dvoretskova
  • L. Medrihan
  • G. Colasante
  • S. Giannelli
  • I. Theka
  • G. Russo
  • L. Mus
  • G. Pezzoli
  • R.R. Gainetdinov
  • F. Benfenati
  • S. Taverna
  • A. Dityatev
  • V. Broccoli

Direct lineage reprogramming through genetic-based strategies enables the conversion of differentiated somatic cells into functional neurons and distinct neuronal subtypes. Induced dopaminergic (iDA) neurons can be generated by direct conversion of skin fibroblasts; however, their in vivo phenotypic and functional properties remain incompletely understood, leaving their impact on Parkinson's disease (PD) cell therapy and modeling uncertain. Here, we determined that iDA neurons retain a transgene-independent stable phenotype in culture and in animal models. Furthermore, transplanted iDA neurons functionally integrated into host neuronal tissue, exhibiting electrically excitable membranes, synaptic currents, dopamine release, and substantial reduction of motor symptoms in a PD animal model. Neuronal cell replacement approaches will benefit from a system that allows the activity of transplanted neurons to be controlled remotely and enables modulation depending on the physiological needs of the recipient; ther

Original languageEnglish
Pages (from-to)3215-3229
JournalJournal of Clinical Investigation
Volume124
Issue number7
DOIs
StatePublished - 2014

ID: 7018671