Autologous transplantation of GDNF-expressing mesenchymal stem cells protects against MPTP-induced damage in cynomolgus monkeys.
Autologous transplantation of GDNF-expressing mesenchymal stem cells protects against MPTP-induced damage in cynomolgus monkeys.
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表达 GDNF 的间充质干细胞的自体移植可保护食蟹猴免受 MPTP 诱导的损伤。
DOI：
10.1038/srep02786
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发表时间：
2013-09-27
影响因子：
4.6
通讯作者：
Zhang, Y. Alex
中科院分区：
文献类型：
--
作者：
Ren, Zhenhua;Wang, Jiayin;Wang, Shuyan;Zou, Chunlin;Li, Xiaobo;Guan, Yunqian;Chen, Zhiguo;Zhang, Y. Alex
胶质细胞源性神经营养因子(GDNF)在帕金森氏病模型中显示出有益的作用。壳核内注射重组GDNF蛋白的双盲临床试验中观察到的温和结果证明了寻找替代给药方法的必要性。在本研究中，我们研究了表达GDNF的自体间充质干细胞(GDNF-MSCs)对MPTP诱导的食蟹猴损伤的保护作用。从猕猴个体骨髓中获得骨髓间充质干细胞，并对其进行基因修饰以表达GDNF。在将GDNF-MSCs单侧植入纹状体和黑质后，用MPTP攻击动物以诱导稳定的全身性帕金森病状态。接受GDNF-MSCs的猴子的对侧肢体的运动功能没有受到影响，但只接受MSCs的猴子的运动功能却没有。移植侧纹状体多巴胺水平升高，多巴胺摄取增强。结果提示，自体骨髓间充质干细胞可能是一种安全的载体，可以运送GDNF以增强黑质纹状体的功能。
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.
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