Abstract
Cell replacement therapy in Parkinson’s disease (PD) aims at re-establishing dopamine neurotransmission in the striatum by grafting dopamine-releasing cells. Chromaffin cell (CC) grafts produce some transitory improvements of functional motor deficits in PD animal models, and have the advantage of allowing autologous transplantation. However, CC grafts have exhibited low survival, poor functional effects and dopamine release compared to other cell types. Recently, chromaffin progenitor-like cells were isolated from bovine and human adult adrenal medulla. Under low-attachment conditions, these cells aggregate and grow as spheres, named chromospheres. Here, we found that bovine-derived chromosphere-cell cultures exhibit a greater fraction of cells with a dopaminergic phenotype and higher dopamine release than CC. Chromospheres grafted in a rat model of PD survived in 57% of the total grafted animals. Behavioral tests showed that surviving chromosphere cells induce a reduction in motor alterations for at least 3 months after grafting. Finally, we found that compared with CC, chromosphere grafts survive more and produce more robust and consistent motor improvements. However, further experiments would be necessary to determine whether the functional benefits induced by chromosphere grafts can be improved, and also to elucidate the mechanisms underlying the functional effects of the grafts.
Highlights
Parkinsons disease (PD) is a neurodegenerative disorder characterized by non-motor and motor symptoms
The physiopathology of PD motor symptoms is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which project to the striatum and release dopamine [1]
In the present study we determined the capacity of chromospheres to survive and to induce motor improvements in 6-OHDA-lesioned animals
Summary
Parkinsons disease (PD) is a neurodegenerative disorder characterized by non-motor and motor symptoms. The latter are the principal targets of current pharmacological therapies, as they are the most disabling for the patients. The physiopathology of PD motor symptoms is associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which project to the striatum and release dopamine [1]. The dopamine levels in the striatum decrease, leading to the classical motor alterations in PD, such as resting tremor, muscle stiffness, paucity of voluntary movements and postural instability [2].
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