Autologous transplantation of GDNF-expressing mesenchymal stem cells protects against MPTP-induced damage in cynomolgus monkeys.

Abstract:

:Glial cell-derived neurotrophic factor (GDNF) has shown beneficial effects in models of Parkinson's disease. The mild results observed in the double-blind clinical trial by intraputamenal infusion of recombinant GDNF proteins warrant a search for alternative delivery methods. In this study, we investigated the function of autologous mesenchymal stem cells (MSCs) expressing GDNF (GDNF-MSCs) for protection against MPTP-induced injury in cynomolgus monkeys. MSCs were obtained from the bone marrow of individual monkeys and gene-modified to express GDNF. Following unilateral engraftment of GDNF-MSCs into the striatum and substantia nigra, the animals were challenged with MPTP to induce a stable systemic Parkinsonian state. The motor functions were spared in the contralateral limbs of monkeys receiving GDNF-MSCs, but not in those receiving MSCs alone. In the striatum of the grafted hemisphere, dopamine levels were higher and dopamine uptake was enhanced. The results suggest that autologous MSCs may be a safe vehicle to deliver GDNF for enhancing nigro-striatum functions.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ren Z,Wang J,Wang S,Zou C,Li X,Guan Y,Chen Z,Zhang YA

doi

10.1038/srep02786

subject

Has Abstract

pub_date

2013-09-27 00:00:00

pages

2786

issn

2045-2322

pii

srep02786

journal_volume

3

pub_type

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