24-07-08(20:23:34)
Authors:
Ole Isacson1, Ivar Mendez2, Angel Viñuela1, Arnar Astradsson1, Penelope Hallett1, Karim Mukhida2, Harold Robertson2, Travis Tierney1, Renn Holness2, Alain Dagher3 and John Q. Trojanowski4
Institutions:
1 Harvard University and McLean Hospital, NINDS Udall Parkinson’s Disease Research Center of Excellence, Boston, MA 02478, USA; 2 Dalhousie University and Queen Elizabeth II Health Sciences Centre, Division of Neurosurgery and Departments of Anatomy & Neurobiology and Pharmacology, Halifax, Canada B3H 3A7; 3 McGill University and Montreal Neurological Institute, McConnell Brain Imaging Centre, Montreal, Canada H3A 2B4; 4Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Ageing of the University of Pennsylvania, NINDS Udall Parkinson’s Disease Research Center of Excellence Philadelphia, PA, USA
Title of abstract : Dopamine neurons transplanted into Parkinson’s disease patients survive for up to 14 years without signs of pathology
Abstract text:
Transplanted human fetal ventral midbrain (VM) neurons have shown functional benefits in some patients with Parkinson´s disease (PD). We here report the postmortem analyses of 5 patients with surviving dopaminergic grafts for 3 – 14 years and show that grafted neurons do not develop the pathology of PD. Fetal VM tissue, obtained from elective abortions, and prepared as a cell suspension, was stereotaxically injected into the putamen of patients with advanced idiopathic Parkinson’s disease. Postmortem analyses of brain tissue were performed using immunohistochemistry and stereological procedures to determine graft survival, phenotypically characterize the grafted neurons, assess immune reaction and determine whether any pathology was associated with grafted neurons. Grafted cells survived for up to 14 years after transplantation. Postmortem analysis with tyrosine hydroxylase (TH), G-protein-coupled-inward rectifying current potassium channel type 2 (Girk2) and Calbindin revealed surviving dopaminergic grafts with reinnervation in all patients. Analysis of a-synuclein, phosphorylated α-synuclein and ubiquitin revealed intracytoplasmic Lewy body inclusions in the substantiae nigrae of the transplanted brains, but not within the grafted cells. The host microglial reaction was minimal and no T-cell infiltration in the host putamen was observed. This study demonstrates that grafted fetal dopaminergic neurons can survive for up to 14 years in the striatum of PD patients without pathological signs of neurodegeneration, such as α-synuclein or ubiquitin positive inclusions. This finding is encouraging for the development of future cell replacement therapies for Parkinson’s disease and has implications for the etiopathogenesis of this neurodegenerative disease.
