Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.
Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.
复制标题
DOI：
10.1016/j.stem.2014.09.017
复制
发表时间：
2014-11-06
期刊：
影响因子：
23.9
通讯作者：
Parmar, Malin
中科院分区：
文献类型：
--
作者：
Grealish, Shane;Diguet, Elsa;Kirkeby, Agnete;Mattsson, Bengt;Heuer, Andreas;Bramoulle, Yann;Van Camp, Nadja;Perrier, Anselme L.;Hantraye, Philippe;Bjorklund, Anders;Parmar, Malin
从人胚胎干细胞（hESC）中产生功能完整的可移植多巴胺神经元的研究已经取得了相当大的进展。在这些细胞可用于帕金森病（PD）的细胞替代疗法之前，重要的是要在动物模型中验证它们的功能特性和功效。在这里，我们提供了一个全面的临床前评估hESC衍生的中脑多巴胺神经元在大鼠模型的PD。我们使用临床相关的MRI和PET成像技术显示了长期存活和功能，并证明了恢复运动功能的功效，其效力与人类胎儿多巴胺神经元相当。此外，我们表明，hESC衍生的多巴胺神经元可以投射足够长的距离用于人类，完全再生中脑到前脑的预测，并支配正确的目标结构。这为使用类似于用胎儿细胞建立的用于治疗帕金森病的那些方法的hESC衍生的多巴胺神经元的临床翻译提供了强有力的临床前支持。hESC-DA的移植物长期存活并恢复体内DA神经传递。hESC-DA的功能效力与人胎儿中脑DA神经元相似。hESC-DA能够长距离、靶特异性地支配宿主脑。提供了hESC衍生的多巴胺神经元在功能上等同于来自胎儿组织的多巴胺神经元的临床前证据，支持继续开发hESC衍生的细胞作为治疗帕金森病的临床方法。
Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson’s disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson’s disease. Transplants of hESC-DA survive long term and restore DA neurotransmission in vivo The functional potency of hESC-DA is similar to human fetal midbrain DA neurons hESC-DA are capable of long-distance, target-specific innervation of the host brain The axonal outgrowth capacity of hESC-DA meets the requirements for use in humans Grealish et al. provide preclinical evidence that hESC-derived dopamine neurons are functionally equivalent to those derived from fetal tissue, supporting continued development of hESC-derived cells as a clinical approach for the treatment of Parkinson’s disease.
登录
查看更多内容
影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
2.9
作者：
PUNDT, LL;KONDOH, T;LOW, WC
通讯作者：
LOW, WC
影响因子：
5.9
作者：
Doi, Daisuke;Samata, Bumpei;Katsukawa, Mitsuko;Kikuchi, Tetsuhiro;Morizane, Asuka;Ono, Yuichi;Sekiguchi, Kiyotoshi;Nakagawa, Masato;Parmar, Malin;Takahashi, Jun
通讯作者：
Takahashi, Jun
影响因子：
14.5
作者：
Mendez, I;Sanchez-Pernaute, R;Isacson, O
通讯作者：
Isacson, O
影响因子：
1.6
作者：
Kuhnast, Bertrand;Damont, Annelaure;Dolle, Frederic
通讯作者：
Dolle, Frederic