PCL/gelatin scaffolds and BETA-BOSWELLIC ACID (BBA) synergistically increase the efficiency of CGR8 stem cells differentiation into dopaminergic neuron: A new paradigm of parkinson s disease cell therapy

IntroductionThe Parkinson’s disease is a degenerative disorder in the central nervous system (CNS), which is distinguished by death of dopamine producing nerve cells resulting in movement disorders. In the ventral mid-brain, namely substantia nigra, dopamine functions as a neurotransmitter that is liberated by neurons and through cell-cell interactions, serves vital for movement control. Levedopa, a dopamine precursor drug, is the current standard of care of symptomatic treatment for Parkinson’s disease. However, the long-term use of the drug is associated with the development of motor fluctuations and dyskinesias. Cell replacement therapy has become the focus of recent research. Cellular therapies aim to deploy fetal dopaminergic neurons as a means to replace the missing dopamine-producing cells. However, ethical limitations and lack of embryos needed for obtaining dopamine-rich embryonic neural cells have limited the use of these cells for Parkinson s disease cell therapy. Therefore, in order to tackle these limitations, many scientists have highlighted the use of pluripotent stem cells to generate dopaminergic neurons.ObjectivesThe present study aims to study the impact of Beta-Boswellic Acid (BBA) coupled with polyε-caprolactone (PCL)/gelatin scaffolds on the dopaminergic differentiation course of CGR8 embryonic stem cells (ESCs).MethodsCGR8 ESCs were cultured on PCL/gelatin scaffolds and a five-step protocol was employed to be promoted the neural differentiation of CGR8 ESCs.ResultsGene expression analysis by real time qPCR demonstrated that PCL/gelatin scaffolds along with BBA treatment impose synergistic effects on the derivation of dopaminergic-like cells from CGR8 ESCs. Reverse phase HPLC confirmed the functionality of the derived neurons by demonstrating the efficient secretion of dopamine in response to stimuli.ConclusionsOur results suggested that the generation of functional dopaminergic-like cells from CGR8 ESCs was increased and supported by PCL/gelatin scaffolds and BBA treatment can heighten the efficiency. This results may open insight into Parkinson s disease cell therapy and provide future directions for tissue engineering with aimed at Parkinson s disease treatment

Keywords:

Parkinson’s disease , PCL/gelatin scaffolds , Beta-boswellic acid , Dopaminergic neurons