A combined cell and gene therapy approach for homotopic reconstruction of midbrain dopamine pathways using human pluripotent stem cells.
Cell Stem Cell
; 29(3): 434-448.e5, 2022 03 03.
Article
in En
| MEDLINE
| ID: mdl-35180398
ABSTRACT
Midbrain dopamine (mDA) neurons can be replaced in patients with Parkinson's disease (PD) in order to provide long-term improvement in motor functions. The limited capacity for long-distance axonal growth in the adult brain means that cells are transplanted ectopically, into the striatal target. As a consequence, several mDA pathways are not re-instated, which may underlie the incomplete restoration of motor function in patients. Here, we show that viral delivery of GDNF to the striatum, in conjunction with homotopic transplantation of human pluripotent stem-cell-derived mDA neurons, recapitulates brain-wide mDA target innervation. The grafts provided re-instatement of striatal dopamine levels and correction of motor function and also connectivity with additional mDA target nuclei not well innervated by ectopic grafts. These results demonstrate the remarkable capacity for achieving functional and anatomically precise reconstruction of long-distance circuitry in the adult brain by matching appropriate growth-factor signaling to grafting of specific cell types.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dopamine
/
Pluripotent Stem Cells
Limits:
Adult
/
Humans
Language:
En
Journal:
Cell Stem Cell
Year:
2022
Document type:
Article
Affiliation country:
Australia