Intrastriatal grafting of glomus cells ameliorates behavioral defects of Parkinsonian rats

Abstract

Parkinson's disease is associated with severe motor dysfunctions due to a progressive loss of dopaminergic neurons in substantia nigra. Transplantation of midbrain neurons from human fetuses to the striatum of patients provides effective treatment for the disease. This type of approach, however, could not be adopted widely due to insufficient supply of fetal materials and the controversial ethical and legal issues. The carotid body is a chemoreceptive organ containing chromaffin-like glomus cells that secrete dopamine (DA) as the neurotransmitter. Here, we report the generation of a clonal dopaminergic cell line of the carotid body using the H-2K b -tsA58 transgenic mouse. Cells from the carotid body were immortalized at the permissive temperatures and in the presence of γ-interferon. The glomus cells were isolated by flow cytometry, and purified to homogeneity by a limited dilution procedure. Upon switching the culture to a nonpermissive condition, the immortal cells ceased to divide, became terminally differentiated and secreted high levels of DA. In rats rendered hemi-Parkinsonian by injection of 6-hydroxydopamine (6-OHDA) into the substantial nigra, intrastriatal grafting of the glomus cells resulted in significant recovery of motor asymmetries and sensorimotor dysfunction. The effects were apparent ∼10 days after transplantation and remained throughout the 4 months of the study. The recovery of behavioral defects was correlated with the ability of cell grafts to release DA in the brain. As none of the existing treatments for Parkinson's disease is completely satisfactory, establishment of a clonal cell line that secretes DA opens a new avenue for the effective control of this neurological disorder.