Stem Cells-Based Therapeutics for Parkinson’s Disease - A Transcriptomic Analyses During Dopaminergic Neuron Differentiation under 3- and 2- Dimensional Environments using Human Embryonic Stem Cells

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease which is caused by many factors including progressive degeneration of dopamine (DA)-secreting neurons which reside in the midbrain substantia nigra compacta (SNc). Current available treatments comprise of intake of DA replenishing drugs or implantation of electrical impulse device. However, the short-term effect of the treatments and risks of side effects haveseverely limited the widespread application of thesetherapiesfor all patients with PD.Hence, human embryonic stem cells (hESCs), which are capable of both self renewal and differentiation into all cell types of human body, could potentially provide a renewable source of surrogate DA neurons for transplantation into PD patients. One of the challenges in using hESCs therapeutically is the establishment of protocols that could effectively direct their differentiation into functionalDA neurons. A specific investigation on the derivation of DA neurons was carried out by usinga three-dimensional (3D)environmentsuch as encapsulation. Characterizationstudyby microarray wasperformed to analyze the global expression profile in 3D-derived DA neurons after 28 days of differentiation. In comparison to the samples of DA neuronal differentiated hESCs under 2D platform for 28 days, the analysis detected the reduced expression of gene that are involved in pluripotency or mitosis but increased expression of genes that are involved in neuronal developments such as Wnt, hedgehogand mitogen-activated protein kinase (MAPK) signaling pathway. The results suggest that the 3D differentiation system may have affected the regulatory or signalling mechanisms which enhanced the rate of differentiation towards ectoderm.