TY - JOUR

T1 - Remote control of induced dopaminergic neurons in parkinsonian rats

AU - Dell'Anno, M.T.

AU - Caiazzo, M.

AU - Leo, D.

AU - Dvoretskova, E.

AU - Medrihan, L.

AU - Colasante, G.

AU - Giannelli, S.

AU - Theka, I.

AU - Russo, G.

AU - Mus, L.

AU - Pezzoli, G.

AU - Gainetdinov, R.R.

AU - Benfenati, F.

AU - Taverna, S.

AU - Dityatev, A.

AU - Broccoli, V.

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

U2 - 10.1172/JCI74664

DO - 10.1172/JCI74664

M3 - Article

VL - 124

SP - 3215

EP - 3229

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 7

ER -