{"id":2730,"date":"2021-11-12T00:00:00","date_gmt":"2021-11-11T16:00:00","guid":{"rendered":"https:\/\/www.cib.cc\/?p=2730"},"modified":"2021-11-12T00:00:00","modified_gmt":"2021-11-11T16:00:00","slug":"jhep-reports%e5%9f%ba%e5%9b%a0%e4%bf%ae%e5%a4%8d%e5%90%8eipsc%e7%94%a8%e4%ba%8e%e6%b2%bb%e7%96%97%e8%82%9d%e8%b1%86%e7%8a%b6%e6%a0%b8%e5%8f%98%e6%80%a7","status":"publish","type":"post","link":"https:\/\/www.cib.cc\/?p=2730","title":{"rendered":"JHEP Reports|\u57fa\u56e0\u4fee\u590d\u540eiPSC\u7528\u4e8e\u6cbb\u7597\u809d\u8c46\u72b6\u6838\u53d8\u6027"},"content":{"rendered":"
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\n \"\u56fe\u7247
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\u57fa\u4e8eiPSC\u7684\u81ea\u4f53\u7ec6\u80de\u6cbb\u7597<\/span><\/p>\n

\uff08Shi, Y., et al. Nat Rev Drug Discov, 2017\uff09<\/span><\/p>\n<\/section>\n

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\u57fa\u4e8eiPSC\u7684\u81ea\u4f53\u7ec6\u80de\u6cbb\u7597<\/strong><\/span><\/p>\n


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iPSC\u5177\u6709\u65e0\u9650\u6269\u589e\u7684\u80fd\u529b\uff0c\u5e76\u4e14\u53ef\u4ee5\u5206\u5316\u4e3a\u6210\u4f53\u6240\u6709\u7ec6\u80de\u7c7b\u578b\uff0c\u53ef\u4e3a\u518d\u751f\u533b\u5b66\u63d0\u4f9b\u65e0\u9650\u7ec6\u80de\u6765\u6e90\u3002\u7ed3\u5408\u57fa\u56e0\u4fee\u9970\u6280\u672f\uff0c\u6211\u4eec\u53ef\u4ee5\u5728\u83b7\u5f97\u75c5\u4eba\u81ea\u8eab\u7684iPSC\u540e\uff0c\u4fee\u590d\u75c5\u4ebaiPSC\u57fa\u56e0\u7ec4\u4e2d\u7684\u7a81\u53d8\uff0c\u5206\u5316\u4e3a\u75be\u75c5\u76f8\u5173\u7ec6\u80de\u7c7b\u578b\uff0c\u7136\u540e\u79fb\u690d\u7ed9\u75c5\u4eba\uff08\u5982\u4e0a\u56fe\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n \u8fd1\u671f\uff0c\u4f5c\u4e3a
\n \u6df1\u6e2f\u521b\u65b0\u5708\u9879\u76ee<\/strong>\u548c
\n \u7ca4\u6e2f\u79d1\u6280\u521b\u65b0\u8054\u5408\u9879\u76ee<\/strong>\u7684\u6210\u679c\u4e4b\u4e00\uff0c\u9999\u6e2f\u5927\u5b66\uff08HKU\uff09\u8054\u5408\u4e09\u542f\u751f\u7269\uff08CIB\uff09\/\u4e09\u542f\u836f\u7269\uff08CIT\uff09\u548c\u4e2d\u56fd\u79d1\u5b66\u9662\u5e7f\u5dde\u751f\u7269\u533b\u836f\u4e0e\u5065\u5eb7\u9662\uff08GIBH\uff09\u5728JHEP Reports\u4e0a\u53d1\u8868\u6587\u7ae0\uff0c\u63d0\u4f9b\u4e86\u57fa\u56e0\u4fee\u590d\u540eiPSC\u7528\u4e8e\u6cbb\u7597\u809d\u8c46\u72b6\u6838\u53d8\u6027\uff08\u4e5f\u79f0\u5a01\u5c14\u900a\u75c5\uff0cWilson’s disease\uff1bWD\uff09\u7684\u6982\u5ff5\u9a8c\u8bc1\u6570\u636e\u3002
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\u25b5 \u9879\u76ee\u6982\u89c8<\/p>\n

\uff08Rui Wei et al., JHEP Reports, 2021 \uff09<\/p>\n<\/section>\n

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\u6982\u5ff5\u9a8c\u8bc1\uff1a\u57fa\u56e0\u4fee\u590d<\/strong>\u540e\u7684iPSC\u6765\u6e90\u809d\u7ec6\u80de\u6cbb\u7597\u809d\u8c46\u72b6\u6838\u53d8\u6027<\/strong><\/p>\n<\/section>\n<\/section>\n

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\u75c5\u56e0<\/strong><\/span><\/p>\n<\/section>\n

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Disease mechanism<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n P\u578b\u94dc\u8f6c\u8fd0ATP\u9176 (ATP7B) \u5728\u809d\u7ec6\u80de\u5185\u67092\u4e2a\u529f\u80fd\uff08\u56fe1\uff09\uff1a\u2460\u88c5\u8f7d\u94dc\u5230\u94dc\u84dd\u86cb\u767d\uff08Cp\uff09\u5f62\u6210Cp-Cu\u590d\u5408\u7269\uff0c\u968f\u540e\u94dc\u968f\u94dc\u84dd\u86cb\u767d\u7ecf\u5faa\u73af\u7cfb\u7edf\u8f93\u9001\u5230\u5168\u8eab\u5404\u4e2a\u5668\u5b98\u5b8c\u6210\u5fc5\u8981\u7684\u751f\u7406\u529f\u80fd\u3002\u2461\u5c06\u809d\u810f\u5185\u591a\u4f59\u7684\u94dc\u901a\u8fc7\u56ca\u6ce1\u8fd0\u8f93\u8f6c\u8fd0\u81f3\u80c6\u6c41\u6392\u51fa\u4f53\u5916\u3002<\/span>
\n

\n <\/section>\n
\n \u809d\u8c46\u72b6\u6838\u53d8\u6027 (WD)\u75c5\u4eba\u7531\u4e8eP\u578b\u94dc\u8f6c\u8fd0ATP\u9176 (ATP7B)\u53d1\u751f\u7a81\u53d8\uff0cATP\u9176\u529f\u80fd\u51cf\u5f31\u6216\u7f3a\u5931\uff0c\u8840\u6e05\u4e2d\u94dc\u84dd\u86cb\u767d\u5408\u6210\u51cf\u5c11\uff0c\u80c6\u9053\u6392\u94dc\u53d7\u963b\uff0c\u8fdb\u800c\u5bfc\u81f4\u8fc7\u91cf\u7684\u94dc\u65e0\u6cd5\u6392\u51fa\u5e76\u5728\u809d\u810f\u4e2d\u79ef\u805a\u3002\u8fc7\u91cf\u94dc\u53ef\u4ea7\u751f\u6c27\u81ea\u7531\u57fa\uff0c\u4f7f\u809d\u7ec6\u80de\u53d7\u635f\uff0c\u7834\u574f\uff0c\u51cb\u4ea1\uff0c\u4ece\u800c\u5bfc\u81f4\u8fdb\u884c\u6027\u809d\u786c\u5316\u548c\u809d\u8870\u7aed\u3002\u8fc7\u91cf\u7684\u94dc\u53ef\u5bfc\u81f4\u591a\u810f\u5668\u53d7\u7d2f\uff0c\u5982\u9525\u4f53\u5916\u7cfb\u75c7\u72b6\u3001\u7cbe\u795e\u75c7\u72b6\u3001\u80be\u635f\u5bb3\u3001Kayser-Fleischer\u73af\u7b49\u30021<\/sup><\/span>
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\u56fe1  Copper Metabolism and ATP7B<\/span><\/p>\n

\uff08Aftab Ala et al., The lancet, 2007\uff09<\/span><\/p>\n


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\n
\n WD\u5728\u4e16\u754c\u8303\u56f4\u7684\u53d1\u75c5\u7387\u4e3a1\/30,000 – 1\/100,000\uff0c\u81f4\u75c5\u57fa\u56e0\u643a\u5e26\u8005\u7ea6\u4e3a1\/90\uff0c\u4ee5\u513f\u7ae5\u548c\u9752\u5c11\u5e74\u53d1\u75c5\u4e3a\u4e3b\uff0c\u662f\u5e38\u89c1\u7684\u9057\u4f20\u6027\u809d\u75c5\u4e4b\u4e00\u3002\u8be5\u75c5\u8fdb\u5165\u4e862018\u5e746\u6708\u56fd\u5bb6\u536b\u5065\u59d4\u8054\u5408\u79d1\u6280\u90e8\u53ca\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\u7b495\u5bb6\u5355\u4f4d\u516c\u5e03\u7684\u300a\u7b2c\u4e00\u6279\u7f55\u89c1\u75c5\u76ee\u5f55\u300b\u3002\u8fd9\u610f\u5473\u7740\u5f00\u53d1WD\u521b\u65b0\u836f\u54c1\u548c\u7597\u6cd5\u5177\u6709
\n \u4f18\u5148\u5ba1\u8bc4\u5ba1\u6279\u3001\u51cf\u514d\u4e34\u5e8a\u8bd5\u9a8c\u3001\u6709\u6761\u4ef6\u6279\u51c6\u4e0a\u5e02\u3001\u5ef6\u957f\u6570\u636e\u4fdd\u62a4\u671f<\/strong>\u7b49\u653f\u7b56\u4f18\u52bf\u3002
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Diagnosis and Treatment<\/span>
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\n WD\u7684\u5b9e\u9a8c\u5ba4\u68c0\u6d4b\u5305\u62ec\u8840\u6e05\u94dc\u84dd\u86cb\u767d\u3001\u8840\u6e05\u94dc\u3001\u5c3f\u94dc\u548c\u809d\u94dc\u7684\u6d4b\u5b9a\uff0c\u4f46\u76f4\u63a5\u68c0\u6d4bATP7B\u7a81\u53d8\u66f4\u4e3a\u53ef\u9760\uff0c\u6709\u52a9\u4e8e\u533a\u5206\u643a\u5e26\u8005\u548c\u60a3\u75c5\u7684\u5e74\u8f7b\u4eba\u3002<\/span>
\n 2<\/sup>
\n

\n <\/section>\n
\n \u76ee\u524d\u9488\u5bf9WD\u7684\u836f\u7269\u4e3b\u8981\u5206\u4e3a2\u79cd\uff0c\u94dc\u87af\u5408\u5242\u6216\u963b\u6b62\u94dc\u5438\u6536\u7684\u950c\u5242\uff08\u88681\uff09\u3002\u5c3d\u7ba1\u94dc\u87af\u5408\u5242\u548c\u950c\u5242\u6cbb\u7597WD\u76ee\u524d\u5df2\u53d6\u5f97\u4e86\u5f88\u4e0d\u9519\u7684\u6210\u6548\uff0c\u4f46\u662f\u5176\u526f\u4f5c\u7528\u4e5f\u4e0d\u5bb9\u5ffd\u89c6\uff0c3 <\/sup>\u67091\/3\u7684WD\u75c5\u4eba\u5bf9\u8fd9\u4e24\u7c7b\u836f\u7269\u65e0\u5e94\u7b54\u30024<\/sup> \u56e0\u6b64\uff0c\u4e9f\u9700\u5f00\u53d1\u9ad8\u6548\u4f4e\u6bd2\u7684\u65b0\u578b\u7597\u6cd5\u3002\u76ee\u524d\u5df2\u6709\u591a\u79cd\u7597\u6cd5\u5728\u5f00\u53d1\u8fc7\u7a0b\u4e2d\uff08\u88682\uff09\uff0c\u5305\u62ec\u4e2d\u836f\u5355\u4f53\uff0c\u5c0f\u5206\u5b50\u5316\u5408\u7269\uff0c\u57fa\u56e0\u7597\u6cd5\u7b49\u3002<\/span>
\n <\/section>\n
\n \u8fd1\u5e74\u6765\uff0ciPSC\u6280\u672f\u7684\u84ec\u52c3\u53d1\u5c55\u4e3a\u8fd9\u7c7b\u9057\u4f20\u75be\u75c5\u4e5f\u63d0\u4f9b\u4e86\u65b0\u7684\u6cbb\u7597\u601d\u8def\u3002<\/span>
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\u25b5 \u88681 \u73b0\u6709\u6cbb\u7597WD\u7684\u836f\u72695<\/sup><\/p>\n<\/section>\n

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\u57fa\u4e8eiPSC\u7684\u521b\u65b0\u7597\u6cd5<\/strong><\/p>\n<\/section>\n

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Cell Therapy<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n \u8bf1\u5bfc\u591a\u80fd\u5e72\u7ec6\u80de\uff08iPSC\uff09\u4e3a\u518d\u751f\u533b\u5b66\u63d0\u4f9b\u4e86\u65e0\u9650\u53ef\u80fd\u3002\u76ee\u524d\uff0c\u4f53\u5916\u57f9\u517b\u5668\u5b98\u4ecd\u7136\u8f83\u4e3a\u56f0\u96be\uff0c\u4f46\u662f\u4f53\u5916\u57f9\u517b\u7ec6\u80de\u7684\u76f8\u5173\u6280\u672f\u5df2\u7ecf\u975e\u5e38\u6210\u719f\u3002\u76ee\u524d\u5df2\u6709\u591a\u4f8b\u57fa\u4e8eiPSC\u7684\u7ec6\u80de\u66ff\u4ee3\u7597\u6cd5\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u3002iPSC\u5177\u6709\u65e0\u9650\u6269\u589e\u7684\u80fd\u529b\uff0c\u5e76\u4e14\u53ef\u4ee5\u5206\u5316\u4e3a\u6210\u4f53\u6240\u6709\u7ec6\u80de\u7c7b\u578b\uff0c\u53ef\u4e3a\u518d\u751f\u533b\u5b66\u63d0\u4f9b\u65e0\u9650\u7ec6\u80de\u6765\u6e90\u3002\u7136\u800c\uff0c\u591a\u6570\u5f02\u4f53\u7ec6\u80de\u79fb\u690d\u4ecd\u7136\u9700\u8981\u6291\u5236\u75c5\u4eba\u514d\u75ab\u7cfb\u7edf\u4ee5\u589e\u957f\u5916\u6e90\u7ec6\u80de\u5728\u75c5\u4eba\u4f53\u5185\u7684\u9a7b\u7559\u65f6\u95f4\uff0c\u957f\u65f6\u95f4\u7684\u514d\u75ab\u6291\u5236\u4f1a\u7ed9\u75c5\u4eba\u5e26\u6765\u611f\u67d3\u4ee5\u53ca\u7f79\u60a3\u80bf\u7624\u7684\u98ce\u9669\u3002\u7ed3\u5408\u57fa\u56e0\u4fee\u9970\u6280\u672f\uff0c\u6211\u4eec\u53ef\u4ee5\u5728\u83b7\u5f97\u75c5\u4eba\u81ea\u8eab\u7684iPSC\u540e\uff0c\u4fee\u590d\u75c5\u4ebaiPSC\u57fa\u56e0\u7ec4\u4e2d\u7684\u7a81\u53d8\uff0c\u5206\u5316\u4e3a\u75be\u75c5\u76f8\u5173\u7ec6\u80de\u7c7b\u578b\uff0c\u7136\u540e\u79fb\u690d\u7ed9\u75c5\u4eba\u3002
\n <\/section>\n
\n \u4e3a\u4e86\u4ece\u6982\u5ff5\u4e0a\u9a8c\u8bc1\u8be5\u7b56\u7565\u662f\u5426\u9002\u7528\u4e8e\u809d\u8c46\u72b6\u6838\u53d8\u6027\uff0c\u6211\u4eec\u9996\u5148\u5efa\u7acb\u4e86\u75c5\u4ebaiPSC\uff0c\u7136\u540e\u5229\u7528CRISPR\/Cas9\u53cassODNs\u4fee\u590d\u4e86ATP7B R778L\u7a81\u53d8(\u56fe3\uff0c\u56fe4)\uff0c\u5e76\u8fdb\u4e00\u6b65\u5c06\u57fa\u56e0\u4fee\u590d\u540e\u7684iPSC\u5206\u5316\u4e3a\u809d\u810f\u7ec6\u80de\u3002\u6211\u4eec\u8bc1\u5b9e\u4e86\u57fa\u56e0\u4fee\u590d\u9006\u8f6c\u4e86R778L\u8868\u578b\uff0c\u8868\u73b0\u4e3a\u6062\u590d\u4e86ATP7B\u5728\u809d\u7ec6\u80de\u5185\u7684\u4e9a\u7ec6\u80de\u5b9a\u4f4d\uff0c\u5e76\u5728\u94dc\u8fc7\u8f7d\u8bd5\u9a8c\u4e2d\u6062\u590d\u4e86\u6cf5\u94dc\u80fd\u529b\u3002\u968f\u540e\uff0c\u6211\u4eec\u5c06\u4fee\u590d\u540e\u7684iPSC\u6765\u6e90\u7684\u809d\u810f\u7ec6\u80de\u79fb\u690d\u81f3
\n Atp7b-\/-<\/sup><\/em> \u514d\u75ab\u7f3a\u9677\u5c0f\u9f20\u4e2d\uff0c\u53d1\u73b0\u8fd9\u4e9b\u7ec6\u80de\u53ef\u663e\u8457\u51cf\u8f7b\u5c0f\u9f20\u7684\u75be\u75c5\u75c7\u72b6\uff0c\u5e76\u4e14\u809d\u635f\u4f24\u51cf\u8f7b\uff0c\u809d\u7ea4\u7ef4\u5316\u964d\u4f4e\uff0c\u809d\u94dc\u542b\u91cf\u964d\u4f4e\u3002
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\u56fe4. Sanger\u6d4b\u5e8f\u786e\u8ba4R778L\u88ab\u4fee\u590d\uff08\u6742\u5408\uff09<\/p>\n<\/section>\n

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1. \u4e2d\u534e\u533b\u5b66\u4f1a\u795e\u7ecf\u75c5\u5b66\u5206\u4f1a\u5e15\u91d1\u68ee\u75c5\u53ca\u8fd0\u52a8\u969c\u788d\u5b66\u7ec4. \u809d\u8c46\u72b6\u6838\u53d8\u6027\u7684\u8bca\u65ad\u4e0e\u6cbb\u7597\u6307\u5357. \u4e2d\u534e\u795e\u7ecf\u5916\u79d1\u6742\u5fd7. 2008;41:566-569.<\/p>\n

2. Fernandes J, Saudubray J-M, Van den Berghe G and Walter JH. Inborn metabolic diseases: diagnosis and treatment: Springer Science & Business Media; 2006.<\/p>\n

3. \u5f20\u8212\u626c\uff0c\u8d75\u7389\u6c9b, \u7f55\u89c1\u75c5\u8bca\u7597\u6307\u5357. 2019\u7248, \u5317\u4eac: \u4eba\u6c11\u536b\u751f\u51fa\u7248\u793e.2019.<\/p>\n

4. orio R, D’Ambrosi M, Marcellini M, Barbera C, Maggiore G, Zancan L, Giacchino R, Vajro P, Marazzi MG, Francavilla R, Michielutti F, Resti M, Frediani T, Pastore M, Mazzarella G, Fusco G, Cirillo F, Vegnente A, Hepatology Committee of Italian Society of Paediatric Gastroenterology H and Nutrition. Serum transaminases in children with Wilson’s disease. J Pediatr Gastroenterol<\/p>\n

Nutr. 2004;39:331-6.<\/p>\n

5.  Jiayin Yang, PhD thesis. HKU<\/p>\n

6. Wei R, Yang J, Cheng CW, Ho WI, Li N, Hu Y, Hong X, Fu J, Yang B, Liu Y, Jiang L, Lai WH, Au KW, Tsang WL, Tse YL, Ng KM, Esteban MA, Tse HF, CRISPR-targeted genome editing of human induced pluripotent stem cell-derived hepatocytes for the treatment of Wilson\u2019s disease, JHEP Reports (2021), doi: https:\/\/doi.org\/10.1016\/j.jhepr.2021.100389.<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7f16\u8f91\uff1aJianquan Zhang<\/span>
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\u57fa\u4e8eiPSC\u7684\u81ea\u4f53\u7ec6\u80de\u6cbb\u7597 \uff08Shi, Y., et al. Nat Rev Drug Discov, 201 […]<\/p>\n","protected":false},"author":1,"featured_media":2731,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[38],"tags":[],"class_list":["post-2730","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/www.cib.cc\/index.php?rest_route=\/wp\/v2\/posts\/2730","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.cib.cc\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.cib.cc\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.cib.cc\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cib.cc\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2730"}],"version-history":[{"count":0,"href":"https:\/\/www.cib.cc\/index.php?rest_route=\/wp\/v2\/posts\/2730\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.cib.cc\/index.php?rest_route=\/wp\/v2\/media\/2731"}],"wp:attachment":[{"href":"https:\/\/www.cib.cc\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2730"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cib.cc\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2730"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cib.cc\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2730"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}