Autologous transplantation of GDNF-expressing mesenchymal stem cells protects against MPTP-induced damage in cynomolgus monkeys.
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.
1] Cell Therapy Center, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, 100053, China [2] Department of Anatomy, Anhui Medical University, Hefei, 230032, China [3].
Zhenhua
Z
Ren
Jiayin
J
Wang
Shuyan
S
Wang
Chunlin
C
Zou
Xiaobo
X
Li
Yunqian
Y
Guan
Zhiguo
Z
Chen
Y Alex
YA
Zhang
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D015870:Gene Expression; D023061:Gene Order; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D020267:MPTP Poisoning / Q000235:genetics* / Q000517:prevention & control / Q000628:therapy*; D008252:Macaca fascicularis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009043:Motor Activity; D015609:Organotechnetium Compounds / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D014182:Transplantation, Autologous; D014326:Tropanes / Q000378:metabolism
D015306:Biogenic Monoamines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D015609:Organotechnetium Compounds; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1