Stem cell researchers have been exploring ways of converting human body cells into neural cells specific to dopamine, an important chemical in the brain. Now it seems they may have found one mix of factors that stimulates this conversion directly. It is hoped that one day such cells may be suitable to replace neurons lost through neurodegeneration in Parkinson’s disease (PD).
PD is becoming a growing threat to today’s aging population, with 127,000 people living with this disease in the UK alone. Characterised by the progressive deterioration of dopamine neurons in an area of the brain called the substantia nigra, patients with PD suffer from debilitating movement difficulties that worsen over time. With no cure known and only a few drugs- e.g. levadopa, a dopamine source – to manage patient symptoms, stem cell research has offered a promising new platform towards finding an effective PD treatment.
Numerous studies so far have shown successful generation of dopamine neurons by reprogramming existing donor cells, using specific proteins called transcription factors. When transplanted into rodent and primate models of Parkinson’s disease, these neurons can help alleviate symptoms.
Unfortunately, the two donor cell types suggested for cell conversion until now face various issues. Embryonic stem cell (ESC) use is ethically controversial, while manipulating mature cells- for instance, fibroblasts – to dedifferentiate first to become induced pluripotent stem cells (iPSCs) is time consuming and expensive.
One potential solution? – Cut out the middle men (the iPSCs).
Xinjian Liu and his team at the Radiation Oncology department at Colorado University, have been working to generate dopamine neurons directly from human fibroblasts, without producing iPSCs first. And it seems they may have identified a suitable combination of transcription factors that makes this happen.
Liu’s group applied transcription factors, Mash1, Ngn2, Sox2, Nurr1 and Pitx3 to human fibroblasts, and found that dopamine neuron-like cells were produced directly. These cells stained positive for dopamine neuron-specific markers and took up and released radioactively-labelled dopamine, just as the control dopamine neurons. When transplanted into rat PD models, the rats’ symptoms improved, with the animals’ rotational behaviour (a measure for their motor abilities) recovering.
Of course, the reality of generating new dopamine neurons that successfully transplant into patients with PD is still far from becoming a viable clinical treatment. Nevertheless, the discovery that Liu’s mix of transcription factors is sufficient to reprogram already mature cells directly into dopamine neuron-like cells presents an exciting step forward towards treating this devastating disorder.
Post by Megan Barrett
Reference: Cell Research, DOI: 10.1038/cr.2011.181
Megan is currently working as an associate writer at a medical communication company. You can follow her on Twitter @Meg_an12.