Subretinal transplantation of forebrain progenitor cells in nonhuman primates: survival and intact retinal function.
Subretinal transplantation of forebrain progenitor cells in nonhuman primates: survival and intact retinal function.
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DOI：
10.1167/iovs.08-2908
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发表时间：
2009-07
影响因子：
4.4
通讯作者：
Lund RD
中科院分区：
文献类型：
--
作者：
Francis PJ;Wang S;Zhang Y;Brown A;Hwang T;McFarland TJ;Jeffrey BG;Lu B;Wright L;Appukuttan B;Wilson DJ;Stout JT;Neuringer M;Gamm DM;Lund RD
基于细胞的治疗在视网膜疾病的啮齿动物模型中挽救了视网膜结构和功能，但转化为临床将需要更多关于在与人眼非常相似的眼睛中移植的后果的信息。因此，我们探讨了供体细胞的行为，使用人皮质神经祖细胞（hNPCctx）引入正常恒河猴视网膜下腔。在平行于人类手术室的条件下，将用绿色荧光蛋白（hNPCctx-GFP）转导的hNPCctx双侧递送到六只正常成年恒河猴的视网膜下腔中。结果测量包括手术成功的临床参数，多焦视网膜电图（mfERG）和植入后3至39天之间进行的组织病理学分析。为了测试GFP转导对细胞生物活性的影响，还将来自同一批次的hNPCctx-GFP注射到RCS大鼠中，并与未标记的hNPCctx进行比较。使用RCS大鼠的研究表明，GFP转导不会改变细胞拯救视力的能力。通过经玻璃体平坦部方法将细胞引入猴视网膜下腔后，所产生的脱离迅速消退，并且视网膜功能在mfERG记录中显示出很少或没有干扰。视网膜结构未受影响，未见炎症或排斥反应迹象。供体细胞在视网膜下腔中以单层形式存活，没有细胞迁移到视网膜内层。人类神经祖细胞可以引入灵长类动物的眼睛没有并发症，使用的方法，将适合外推到人类患者。
Cell-based therapy rescues retinal structure and function in rodent models of retinal disease, but translation to clinic will require more information about consequences of transplantation in an eye closely resembling the human eye. Therefore we explored donor cell behavior using human cortical neural progenitor cells (hNPCctx) introduced into the subretinal space of normal rhesus macaques. hNPCctx transduced with Green Fluorescent Protein (hNPCctx-GFP) were delivered bilaterally into the subretinal space of six normal adult rhesus macaques under conditions paralleling those of the human operating room. Outcome measures included clinical parameters of surgical success, multifocal electroretinogram (mfERG) and histopathological analyses performed between 3 and 39 days post-engraftment. To test the effects of GFP transduction on cell bioactivity, hNPCctx –GFP from the same batch were also injected into RCS rats and compared with non-labeled hNPCctx. Studies using RCS rats indicated that GFP transduction did not alter the ability of the cells to rescue vision. After cells were introduced into the monkey subretinal space by a pars plana transvitreal approach, the resulting detachment was rapidly resolved and retinal function showed little or no disturbance in mfERG recordings. Retinal structure was unaffected and no signs of inflammation or rejection were seen. Donor cells survived as a single layer in the subretinal space and no cells migrated into the inner retina. Human neural progenitor cells can be introduced into a primate eye without complication, using an approach that would be suitable for extrapolation to human patients.
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影响因子：
4.2
作者：
Tezel, Tongalp H.;Del Priore, Lucian V.;Kaplan, Henry J.
通讯作者：
Kaplan, Henry J.
影响因子：
3.7
作者：
Gamm, David M.;Wang, Shaomei;Lu, Bin;Girman, Sergei;Holmes, Toby;Bischoff, Nicholas;Shearer, Rebecca L.;Sauve, Yves;Capowski, Elizabeth;Svendsen, Clive N.;Lund, Raymond D.
通讯作者：
Lund, Raymond D.
DOI：
10.1089/clo.2006.8.189
发表时间：
2006-09-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Lund, Raymond D.;Wang, Shaomei;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
3
作者：
Svendsen, CN;ter Borg, MG;Caldwell, MA
通讯作者：
Caldwell, MA
影响因子：
5.3
作者：
Sapru, MK;Yates, JW;Bohn, MC
通讯作者：
Bohn, MC