RT Journal Article
T1 Effects of Rho kinase inhibitors on grafts of dopaminergic cell precursors in a rat model of Parkinson's Disease
A1 Rodríguez Pallares, Jannette
A1 Rodríguez Pérez, Ana Isabel
A1 Muñoz Patiño, Ana María
A1 Parga Martín, Juan Andrés
A1 Toledo Aral, Juan J.
A1 Labandeira García, José Luis
K1 Rho kinase
K1 Cell therapy
K1 Dopamine
K1 Neuroprotection
K1 Parkinson
K1 Striatum
K1 Transplantation
AB In models of Parkinson’s disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axonstabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protectagainst dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated. In thepresent study, treatment of dopaminergic cell suspension with ROCK inhibitors yielded significant decreases in the number of surviving dopaminergic neurons, in the density of graft-derived dopaminergic fibers, and in graft vascularization. Dopaminergic neuron death also markedly increased in primarymesencephalic cultures when the cell suspension was treated with ROCK inhibitors before plating,which suggests that decreased angiogenesis is not the only factor leading to cell death in grafts. Interestingly, treatment of the host 6-hydroxydopamine-lesioned rats with ROCK inhibitors induced aslight, nonsignificant increase in the number of surviving neurons, as well as marked increases in thedensity of graft-derived dopaminergic fibers and the size of the striatal reinnervated area. The studyfindings discourage treatment of cell suspensions before grafting. However, treatment of the hostinduces a marked increase in graft-derived striatal reinnervation. Because ROCK inhibitors have alsoexerted neuroprotective effects in several models of PD, treatment of the host with ROCK inhibitors,currently used against vascular diseases in clinical practice, before and after grafting may be a usefuladjuvant to cell therapy in PD
PB Wiley
SN 2157-6564
YR 2016
FD 2016
LK http://hdl.handle.net/10347/22839
UL http://hdl.handle.net/10347/22839
LA eng
NO Rodriguez-Pallares, J., Rodriguez-Perez, A.I., Muñoz, A., Parga, J.A., Toledo-Aral, J.J. and Labandeira-Garcia, J.L. (2016), Effects of Rho Kinase Inhibitors on Grafts of Dopaminergic Cell Precursors in a Rat Model of Parkinson's Disease. STEM CELLS Translational Medicine, 5: 804-815. doi:10.5966/sctm.2015-0182
NO This work was supported by Spanish Ministry of Health (PI12/00798 and RD12/0019/0020) and Spanish Ministry of Economy and Competitiveness (BFU2012-3708)
DS Minerva
RD 25 abr 2026