Reducing alcohol and/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform.
Reducing alcohol and/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform.
复制标题
通过基于表皮干细胞的基因递送平台减少酒精和/或可卡因诱导的奖赏和毒性。
DOI：
10.1038/s41380-021-01043-y
复制
发表时间：
2021-09
影响因子：
11
通讯作者：
Xu M
中科院分区：
文献类型：
--
作者：
Kong Q;Li Y;Yue J;Wu X;Xu M
酒精使用障碍（AUD）是最重要的公共卫生问题之一。酒精也经常与可卡因一起滥用。对于AUD和/或可卡因共滥用的治疗存在巨大的未满足的需求。我们最近证明，通过CRISPR介导的基因组编辑工程改造的小鼠表皮干细胞产生的皮肤移植物可以作为基因递送平台移植到小鼠身上。在这里，我们表明，胰高血糖素样肽-1（GLP 1）基因的表达由表皮干细胞传递衰减酒精诱导的药物服用和寻求以及自愿口服酒精消费的发展和恢复。来自皮肤移植物的GLP 1降低了酒精诱导的丘脑核中多巴胺水平的增加。在探索该平台在减少同时使用药物方面的潜力时，我们开发了一种新的共移植程序，用于修饰的人丁酰胆碱酯酶（hBChE）和GLP 1表达细胞。表皮干细胞衍生的hBChE和GLP 1减少了酒精和可卡因联合给药引起的吸毒和毒性的获得。这些结果意味着，通过皮肤移植的皮肤基因传递可能会增加一个新的选择，以治疗药物滥用和共同滥用。
Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.
登录
查看更多内容
影响因子：
28.1
作者：
Li, Yuanyuan;Kong, Qingyao;Wu, Xiaoyang
通讯作者：
Wu, Xiaoyang
影响因子：
4.7
作者：
McLaughlin I;Dani JA;De Biasi M
通讯作者：
De Biasi M
影响因子：
5.3
作者：
Maniscalco, James W.;Zheng, Huiyuan;Rinaman, Linda
通讯作者：
Rinaman, Linda
DOI：
10.1073/pnas.0507332102
发表时间：
2005-11-15
影响因子：
11.1
作者：
Pan, YM;Gao, DQ;Zhan, CG
通讯作者：
Zhan, CG
影响因子：
3.1
作者：
Kastin, AJ;Akerstrom, V;Pan, WH
通讯作者：
Pan, WH