Development of Neural Stem Cell-Based Therapies for Parkinson’s Disease

Abstract

Neural stem cell (NSC)-based therapies, such as cell transplantation, are an emerging strategy for restoring neuronal function in Parkinson's disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Advanced researches on the microenvironment of grafted cells will promote clinical applications of NSCs for neurological disorders. A novel cell culture model of the neurovascular network was therefore devised to investigate autocrine, paracrine, and juxtacrine signaling in the neurovascular unit generated by NSCs and vascular endothelial cells. Preclinical studies using cutting-edge technologies, including cellular reprogramming, advancement in scaffolds for brain tissue engineering, image-guided injection, and noninvasive monitoring of tissue regeneration will pave the way for successful clinical trials of NSC-based therapies for PD. Once the implanted or regenerated DA neurons are integrated into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration.

Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress

“…NSCs have a fundamental role after nervous tissue damage as they have the potential for regeneration owing to their capacity of self-renewal and differentiation into neurons 8,32 . However, this extraordinary capacity is limited under pathological conditions due to the factors present in the wounded microenvironment that can affect NSCs survival, proliferation and differentiation [33][34][35][36] .…”

Comparative transcriptome analysis of Parkinson’s disease and Hutchinson-Gilford progeria syndrome reveals shared susceptible cellular network processes

“…GO terms only show up because of overlap with brain and skin processes. regulation of cell projection assembly down in PD, majority of genes down in HGPS (a few up) cell projection organization genes from cell projection GO terms as modifiers of neurodegeneration in PD [ 73 ]; cell projection in GO analysis of progerin-associated proteins [ 74 ] viral genome replication down in PD, majority of genes down in HGPS (a few up) viral processes Viral immunity decreases during aging [ 75 ] myoblast development down in PD, majority of genes down in HGPS (a few up) nervous system development PD might be associated with neurodevelopment [ 76 ] morphogenesis of an endothelium down in PD, majority of genes down in HGPS (a few up) endothelial morphogenesis application in neural stem cell-based therapy for PD [ 77 ] circadian rhythm down in PD, majority of genes down in HGPS (a few up) circadian rhythm Decrease of circadian rhythm associated with neurodegenerative disorders [ 78 ] and premature aging [ 79 ] dopamine biosynthetic process down in PD, up in HGPS dopamine dopamine in diagnosis and treatment of PD [ 80 ]; dopamine-specific processes in progerin-induced aging [ 13 ] regulation of cytokinesis down in PD, majority of genes up in HGPS (a few down) cytokinesis decrease of the number of cell divisions related to aging [ 81 ] response to electrical stimulus down in PD, majority of genes up in HGPS (a few down) electrical stimulus effect of electrical stimulation on gait in PD patients [ 82 …”

Effect of Inflammatory Stress on Neural Stem Cells Behaviour: A Rescue Effect of Phosphatidylcholine by Modulating Neuronal Plasticity.

“…NSCs have a fundamental role after nervous tissue damage as they have the potential for regeneration owing to their capacity of self-renewal and differentiation into neurons 8, 29 . However, this extraordinary capacity is limited under pathological conditions due to the factors present in the wounded microenvironment that can affect NSCs survival, proliferation and differentiation 30,31,32,33 .…”