Programming iPSCs show promise in Parkinson’s Disease

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A collaborative study led by Prof. Mehdi Shamsaraa and Prof. Mohammad Massumi has developed a protocol to differentiate induced Pluripotent Stem Cells (iPSCs) to dopaminergic neurons. With recent advancements in stem cells and reprogramming technologies, this finding may have particular relevance on the development of stem cell therapies for Parkinson’s disease.

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder, the etiology of which remains largely unknown. The primary clinical feature of the disease is progressive impairment of voluntary motor control, which is caused by a loss of midbrain substantia nigra dopamine (DA) neurons.

In the study, published in Neuroscience Letters, the team used iPSCs expressing two master dopaminergic transcription factors: Nurr1 and Pitx3, to generate functional in vitro DAergic-like neurons. After establishment and characterization of iPSCs from mouse fibroblasts, the cells were transduced by NURR1- and PITX3-harboring lentiviruses. The Nurr1/Pitx3 -iPSCs were differentiated through a five-stage protocol to generate DAergic-like neurons. The results confirmed the efficient expression of DAergic neuron markers and the generated cells could exclusively synthesize and secrete DA in response to secretagogues.

Thus, the authors conclude this provides evidence of the ability to programme iPSCs into functional DAergic-like neurons.

Source: Efficient generation of Dopaminergic-like neurons by overexpression of Nurr1 and Pitx3 in mouse induced Pluripotent Stem Cells. Salemeh Salemi et al., Neuroscience Letters (May 2016).