Tissue engineered nigrostriatal pathway for treatment of Parkinson's disease

Journal of Tissue Engineering and Regenerative Medicine
Laura A StruzynaD Kacy Cullen

Abstract

The classic motor deficits of Parkinson's disease are caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of their long-distance axonal projections that modulate the striatum. Current treatments only minimize the symptoms of this disconnection as there is no approach capable of replacing the nigrostriatal pathway. We are applying microtissue engineering techniques to create living, implantable constructs that mimic the architecture and function of the nigrostriatal pathway. These constructs consist of dopaminergic neurons with long axonal tracts encased within hydrogel microcolumns. Microcolumns were seeded with dopaminergic neuronal aggregates, while lumen extracellular matrix, growth factors, and end targets were varied to optimize cytoarchitecture. We found a 10-fold increase in axonal outgrowth from aggregates versus dissociated neurons, resulting in remarkable axonal lengths of over 6 mm by 14 days and 9 mm by 28 days in vitro. Axonal extension was also dependent upon lumen extracellular matrix, but did not depend on growth factor enrichment or neuronal end target presence. Evoked dopamine release was measured via fast scan cyclic voltammetry and synapse formation wit...Continue Reading

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Citations

Jan 17, 2019·Tissue Engineering. Part a·H Isaac ChenDouglas H Smith
Dec 4, 2019·Frontiers in Neuroscience·Michel Modo
Apr 16, 2019·Frontiers in Neuroscience·Dayo O AdewoleD Kacy Cullen
Jan 15, 2020·NPJ Parkinson's Disease·James P HarrisD Kacy Cullen
Jun 19, 2020·Npj Regenerative Medicine·Suradip DasD Kacy Cullen
Nov 14, 2019·Neural Regeneration Research·Rocío Fernandez-SerraDaniel González-Nieto
May 8, 2020·International Journal of Molecular Sciences·Matteo BordoniCristina Cereda
Dec 18, 2020·Frontiers in Bioengineering and Biotechnology·Kate V PanzerD Kacy Cullen
Jan 13, 2021·Tissue Engineering. Part a·Patricia Zadnik SullivanAli K Ozturk
Feb 14, 2021·Npj Regenerative Medicine·Suradip DasD Kacy Cullen
Jan 8, 2021·NPJ Parkinson's Disease·James P HarrisD Kacy Cullen
Oct 28, 2019·IScience·D Kacy CullenH Isaac Chen
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