Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease

TY - JOUR

T1 - Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease

AU - Grealish, Shane

AU - Diguet, Elsa

AU - Kirkeby, Agnete

AU - Mattsson, Bengt

AU - Heuer, Andreas

AU - Bramoulle, Yann

AU - Van Camp, Nadja

AU - Perrier, Anselme L.

AU - Hantraye, Philippe

AU - Björklund, Anders

AU - Parmar, Malin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease.

AB - Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease.

UR - http://www.scopus.com/inward/record.url?scp=84922662454&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2014.09.017

DO - 10.1016/j.stem.2014.09.017

M3 - Journal article

C2 - 25517469

AN - SCOPUS:84922662454

SN - 1934-5909

VL - 15

SP - 653

EP - 665

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 5

ER -