Open AccessGutting the brain of inflammation: A key role of gut microbiome in human umbilical cord blood plasma therapy in Parkinson's disease model
Author(s) -
Lee JeaYoung,
Tuazon Julian P.,
Ehrhart Jared,
Sanberg Paul R.,
Borlongan Cesario V.
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14429
Subject(s) - substantia nigra , pars compacta , mptp , stem cell , transplantation , inflammation , dopaminergic , umbilical cord , medicine , immunology , biology , dopamine , microbiology and biotechnology
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.