Document Type
Article
Publication Date
2019
Keywords
cord blood, gut microbiome, neurodegeneration, neuroinflammation, plasma
Digital Object Identifier (DOI)
https://doi.org/10.1111/jcmm.14429
Abstract
Current therapies for Parkinson's disease (PD), including L-3,4-dihydroxyphenylalanine (L-DOPA), and clinical trials investigating dopaminergic cell transplants, have generated mixed results with the eventual induction of dyskinetic side effects. Although human umbilical cord blood (hUCB) stem/progenitor cells present with no or minimal capacity of differentiation into mature dopaminergic neurons, their transplantation significantly attenuates parkinsonian symptoms likely via bystander effects, specifically stem cell graft-mediated secretion of growth factors, anti-inflammatory cytokines, or synaptic function altogether promoting brain repair. Recognizing this non-cell replacement mechanism, we examined here the effects of intravenously transplanted combination of hUCB-derived plasma into the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rat model of PD. Animals received repeated dosing of either hUCB-derived plasma or vehicle at 3, 5 and 10 days after induction into MPTP lesion, then behaviourally and immunohistochemically evaluated over 56 days post-lesion. Compared to vehicle treatment, transplantation with hUCB-derived plasma significantly improved motor function, gut motility and dopaminergic neuronal survival in the substantia nigra pars compacta (SNpc), which coincided with reduced pro-inflammatory cytokines in both the SNpc and the intestinal mucosa and dampened inflammation-associated gut microbiota. These novel data directly implicate a key pathological crosstalk between gut and brain ushering a new avenue of therapeutically targeting the gut microbiome with hUCB-derived stem cells and plasma for PD.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Cellular and Molecular Medicine, v. 23, issue 8, p. 5466-5474
Scholar Commons Citation
Lee, Jea-Young; Tuazon, Julian P.; Ehrhart, Jared; Sanberg, Paul R.; and Borlongan, Cesar V., "Gutting the Brain of Inflammation: A Key Role of Gut Microbiome in Human Umbilical Cord Blood Plasma Therapy in Parkinson's Disease Model" (2019). Neurosurgery and Brain Repair Faculty Publications. 7.
https://digitalcommons.usf.edu/nbr_facpub/7
