The therapeutic use of clonal neural stem cells in experimental Parkinson´s disease.

Abstract

Background: Parkinson´s disease (PD), the second most common neurodegenerative disease in the world, is characterized by the death or impairment of dopaminergic neurons (DAn) in the substantia nigra pars compacta and dopamine depletion in the striatum. Currently, there is no cure for PD, and treatments only help to reduce the symptoms of the disease, and do not repair or replace the DAn damaged or lost in PD. Cell replacement therapy (CRT) seeks to relieve both pathological and symptomatic PD manifestations and has been shown to have beneficial effects in experimental PD models as well as in PD patients, but an apt cell line to be used in the treatment of PD has yet to be established. The purpose of this study was to examine the effects of the transplantation of hVM1 clone 32 cells, a bankable line of human neural stem cells (hNSCs), in a PD mouse model at four months post-transplant.

Methods: Adult (five month-old) C57BL/6JRccHsd male mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and subsequently transplanted with hVM1 clone 32 cells, or buffer, in the left striatum. Four months post-transplant, behavioral effects were explored using the open field and paw print tests, and histological analyses were performed.

Results: Transplantation of hVM1 clone 32 cells rescued dopaminergic nigrostriatal populations in adult Parkinsonian mice. Motor and neurological deterioration were observed in buffer-treated mice, the latter of which had a tendency to improve in hNSC-transplanted mice. Detection of mast cell migration to the superficial cervical lymph nodes in cell-transplanted mice denoted a peripheral effect. Transplantation of hNSCs also rescued neuroblast neurogenesis in the subgranular zone, which was correlated with dopaminergic recovery and is indicative of local recovery mechanisms.

Conclusions: In this proof-of-concept study, the transplantation of hVM1 clone 32 cells provided neuroprotection in adult Parkinsonian mice by restoring the dopaminergic nigrostriatal pathway and hippocampal neurogenesis, demonstrating the efficacy of cell replacement therapy as a treatment for PD.