Editors' ChoiceParkinson’s Disease

Remaking the Brain with Stem Cells

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Science Translational Medicine  16 Jan 2013:
Vol. 5, Issue 168, pp. 168ec10
DOI: 10.1126/scitranslmed.3005664

Parkinson’s disease is a debilitating neurodegenerative disorder that affects over one million people in the United States. The key pathogenic process in Parkinson’s disease is a loss of cells that produce dopamine in the midbrain. Low dopamine levels disrupt the nigrostriatal pathway, causing a communication breakdown within the brain that leads to loss of motor control and the ability to generate smooth limb movements. The mainstays of therapy for Parkinson’s disease are treatments to boost dopamine signaling in the brain and to help control involuntary movements, but there are many side effects with these treatments. In a new study, Hayashi et al. use dopaminergic neurons derived from autologous mesenchymal stem cells (MSCs) to treat Parkinson’s disease in monkeys.

Cell-based therapies have shown promise in animal and human studies for treating Parkinson’s disease. Most notably, early studies found that the implantation of human fetal midbrain tissue into the brains of a few Parkinson’s patients improved symptoms of the disease in some patients. However, this approach remained impractical clinically because of the limited availability of tissues and ethical concerns. Therefore, there has been much interest in finding other sources of dopamine-producing cells. In their study, Hayashi et al. harvested MSCs from the bone marrow of 10 monkeys. These cells were cultured in vitro and differentiated into dopamine-producing neuron-like cells by transfecting the MSCs with the Notch1 intracellular domain and then stimulating the cells with a combination of growth factors and cytokines.

The researchers induced unilateral Parkinson’s disease in the monkeys by injecting a neurotoxin into one-half of the brain. They then transplanted the MSC-derived dopamine-producing neuron-like cells at multiple brain locations and evaluated them for engraftment at time points up to 8 months. Monkeys treated with the cell transplants showed a substantial improvement in behavioral measurements of motor function. Using positron emission tomography and histological analysis, the authors found that there was a marked increase in dopamine activity in regions where cells had engrafted. Importantly, they did not find any evidence of tumorigenesis in the animals due to the cell therapy treatment.

The Hayashi et al. study demonstrates the potential of cell-based therapy for treating a monkey model of Parkinson’s disease. Further work is needed to more fully evaluate this type of cell therapy and to improve it sufficiently so that ultimately it may be useful for treating patients with Parkinson’s disease.

T. Hayashi et al., Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques. J. Clin. Invest. 123, 272–284 (2013). [ABSTRACT]

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