Understanding Parkinson’s Disease through the Use of Cell Reprogramming

Abstract

Recent progress in the field of somatic cell reprogramming offers exciting new possibilities for the study and treatment of Parkinson's disease (PD). Reprogramming technology offers the ability to untangle the diverse contributing risk factors for PD, such as ageing, genetics and environmental toxins. In order to gain novel insights into such a complex disease, cell-based models of PD should represent, as closely as possible, aged human dopaminergic neurons of the substantia nigra. However, the generation of high yields of functionally mature, authentic ventral midbrain dopamine (vmDA) neurons has not been easy to achieve. Furthermore, ensuring cells represent aged rather than embryonic neurons has presented a significant challenge. To date, induced pluripotent stem (iPS) cells have received much attention for modelling PD. Nonetheless, direct reprogramming strategies (either to a neuronal or neural stem/progenitor fate) represent a valid alternative that are yet to be extensively explored. Direct reprogramming is faster and more efficient than iPS cell reprogramming, and appears to conserve age-related markers. At present, however, protocols aiming to derive authentic, mature vmDA neurons by direct reprogramming of adult human somatic cells are sorely lacking. This review will discuss the strategies that have been employed to generate vmDA neurons and their potential for the study and treatment of PD.

Reconstructing human pancreatic differentiation by mapping specific cell populations during development

“…However, the cells generated in vitro from hPSC do not seem fully differentiated and in some cases, display a fetal phenotype rather than an adult one. This is the case for hepatocytes ( Baxter et al, 2015 ), cardiomyocytes ( Karakikes et al, 2015 ), neurons ( Playne and Connor, 2017 ) and pancreatic beta cells ( Hrvatin et al, 2014 ). These partial successes could be in part due to the limited knowledge on human cell development.…”

Biomarker Research in Parkinson’s Disease Using Metabolite Profiling

“…Animal models of PD have been used to study markers of dopaminergic degeneration, changes in receptors or alteration in blood flow or energy consumption using PET or NMR imaging [ 103 ]. In vitro models of PD include cell and slice culture models [ 104 ] and most recently also differentiated neurons from human iPS cells [ 105 , 106 ]. However, only a few experimental studies used a metabolomic approach to identify novel biomarkers of PD.…”

3D Bioprinting Pluripotent Stem Cell Derived Neural Tissues Using a Novel Fibrin Bioink Containing Drug Releasing Microspheres

“…This discovery has enabled the study of many diseases as these stem cell lines can be derived from patients suffering from different diseases and disorders. Using patient derived hiPSCs lines and differentiating them into a target tissue type is a powerful way to study diseases, including those affecting the nervous system -like Alzheimer's and Parkinson's (Playne and Connor, 2017;Cheng et al, 2018Cheng et al, , 2019Penney et al, 2019). Often, research on hiPSC models of these diseases is conducted in 2D, despite brain tissue possessing a complex 3D structure.…”