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世界生命科學前沿動態(tài)周報（八十五）
干細胞方法治療失明成功用于老鼠
科技日報Science Daily 2013年1月7日：牛津大學納菲爾德臨床神經科學系的教授Robert MacLaren和新加坡國立大學醫(yī)院的眼科醫(yī)生Mandeep Singh研究發(fā)現，將發(fā)育中的細胞移植入失明老鼠的眼睛后，能夠重建其視網膜的整個光敏層?！睹绹鴩铱茖W院院刊》在線發(fā)表了他們的相關研究結果。
研究人員稱這個方法可以幫助治療色素性視網膜炎患者，這類患者因視網膜的光敏細胞逐漸死亡導致漸進性失明。他們用最近似的失明老鼠模型做實驗，兩周后發(fā)現將發(fā)育細胞移植入眼后在視網膜上重建了整個光敏層，且老鼠可以看見東西了。他們使用的是老鼠發(fā)育中的視網膜細胞初期的前體細胞。瞳孔收縮實驗發(fā)現12只老鼠中有10只老鼠對光的瞳孔收縮反應提高，表明老鼠的視網膜再次有了光感，且經視神經盤傳至了大腦。
Dr. Singh說，“我們發(fā)現如果將足夠數量的細胞移植在一起，不僅能產生光敏性，而且還能再生出產生視力所需的連接。MacLaren稱他們想使用iPSCs來進行研究，希望可以實現細胞療法治療人類失明。這些來自患者體內的細胞如皮膚或血液細胞產生的干細胞可以直接形成視網膜細胞的前體細胞。他還稱這是前人實現的結果，將來在患者上的應用如同探囊取物。下一步的目標是在病人體內找到可靠的細胞來源以便提供細胞移植所需的干細胞。
點評: 用iPSCs來進行色素性視網膜炎研究目前只是實現了此類老鼠再次獲得光感，但如何解決再生出產生視力所需的連接仍是主要的難題。
相關文獻：
Reversal of end-stage retinal degeneration and restoration of visual function by transplantation
Author: Mandeep S. Singha, Peter Charbel Issaa, Rachel Butlera, Chris Martinb, Daniel M. Lipinskia, Sumathi Sekarana, Alun R. Barnarda, and Robert E. MacLarena,c,d,1
Edited by Constance L. Cepko, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, and approved December 7, 2012 (received for review November 24, 2011)
Abstract
One strategy to restore vision in retinitis pigmentosa and age-related macular degeneration is cell replacement. Typically, patients lose vision when the outer retinal photoreceptor layer is lost, and so the therapeutic goal would be to restore vision at this stage of disease. It is not currently known if a degenerate retina lacking the outer nuclear layer of photoreceptor cells would allow the survival, maturation, and reconnection of replacement photoreceptors, as prior studies used hosts with a preexisting outer nuclear layer at the time of treatment. Here, using a murine model of severe human retinitis pigmentosa at a stage when no host rod cells remain, we show that transplanted rod precursors can reform an anatomically distinct and appropriately polarized outer nuclear layer. A trilaminar organization was returned to rd1 hosts that had only two retinal layers before treatment. The newly introduced precursors were able to resume their developmental program in the degenerate host niche to become mature rods with light-sensitive outer segments, reconnecting with host neurons downstream. Visual function, assayed in the same animals before and after transplantation, was restored in animals with zero rod function at baseline. These observations suggest that a cell therapy approach may reconstitute a light-sensitive cell layer de novo and hence repair a structurally damaged visual circuit. Rather than placing discrete photoreceptors among preexisting host outer retinal cells, total photoreceptor layer reconstruction may provide a clinically relevant model to investigate cell-based strategies for retinal repair.