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Journal article
Restoring lost nigrostriatal fibers in Parkinson’s disease based on clinically-inspired design criteria
Brain research bulletin, v 175, pp 168-185
Oct 2021
PMID: 34332016
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Parkinson’s disease is a neurodegenerative disease affecting around 10 million people worldwide. The death of dopaminergic neurons in the substantia nigra and the axonal fibers that constitute the nigrostriatal pathway leads to a loss of dopamine in the striatum that causes the motor symptoms of this disease. Traditional treatments have focused on reducing symptoms, while therapies with human fetal or stem cell-derived neurons have centered on implanting these cells in the striatum to restore its innervation. An alternative approach is pathway reconstruction, which aims to rebuild the entire structure of neurons and axonal fibers of the nigrostriatal pathway in a way that matches its anatomy and physiology. This type of repair could be more capable of reestablishing the signaling mechanisms that ensure proper dopamine release in the striatum and regulation of other motor circuit regions in the brain. In this manuscript, we conduct a review of the literature related to pathway reconstruction as a treatment for Parkinson’s disease, delve into the limitations of these studies, and propose the requisite design criteria to achieve this goal at a human scale. We then present our tissue engineering-based platform to fabricate hydrogel-encased dopaminergic axon tracts in vitro for later implantation into the brain to replace and reconstruct the pathway. These tissue-engineered nigrostriatal pathways (TE-NSPs) can be characterized and optimized for cell number and phenotype, axon growth lengths and rates, and the capacity for synaptic connectivity and dopamine release. We then show original data of advances in creating these constructs matching clinical design criteria using human iPSC-derived dopaminergic neurons and a hyaluronic acid hydrogel. We conclude with a discussion of future steps that are needed to further optimize human-scale TE-NSPs and translate them into clinical products.
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Details
- Title
- Restoring lost nigrostriatal fibers in Parkinson’s disease based on clinically-inspired design criteria
- Creators
- Wisberty J. Gordián-Vélez - Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United StatesDimple Chouhan - Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesRodrigo A. España - Drexel UniversityH. Isaac Chen - University of PennsylvaniaJason A. Burdick - University of PennsylvaniaJohn E. Duda - University of PennsylvaniaD. Kacy Cullen - University of Pennsylvania
- Publication Details
- Brain research bulletin, v 175, pp 168-185
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000686894000001
- Scopus ID
- 2-s2.0-85111666348
- Other Identifier
- 991019167794104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences