In the last decade, direct reprogramming has emerged as a novel strategy to obtain mature and functional dopamine neurons from somatic cells. This approach could overcome issues linked to the use of human pluripotent stem cells such as ethical concerns and safety problems that can arise from the overgrowth of undifferentiated cells after transplantation. Several conversion methodologies have been developed to obtain induced DA neurons (iDANs) or induced DA neuron progenitors (iDPs). iDANs have also proved to successfully integrate in mice striatum, alleviating Parkinson's disease (PD) motor symptoms. In the next decade, human iDANs and/or iDPs could be translated to clinic to achieve a patient-tailored therapy, but current critical issues hinder this goal, such as the low conversion rate of adult human fibroblasts and the risks associated with lentiviral delivery of conversion factors. In this study, we summarize the strategies and recent improvements developed for the generation of mouse and human iDANs/iDPs. Furthermore, we discuss the more recent application of in vivo direct conversion, which may enable clinical therapies for PD by means of brain in situ delivery of dopaminergic reprogramming transcription factors.
Keywords: Parkinson's disease; cell reprogramming; cell therapy; transdifferentiation.