通過移植成體干細(xì)胞治療甚至治愈老年性黃斑變性,，近期獲得重要的臨床進(jìn)展。該研究已于3月25日發(fā)表在Stem Cells上,，喬治敦大學(xué)醫(yī)學(xué)中心的研究人員已經(jīng)首次證實(shí)具有將人類誘導(dǎo)多能干細(xì)胞培育成視網(wǎng)膜細(xì)胞的能力,。
老年性黃斑變性又稱年齡相關(guān)性黃斑變性(AMD)，主要表現(xiàn)為視網(wǎng)膜色素上皮細(xì)胞對視細(xì)胞外節(jié)盤膜吞噬消化能力下降,，結(jié)果使未被完全消化的盤膜殘余小體潴留于基底部細(xì)胞原漿中,，并向細(xì)胞外排出，沉積于Bruch膜,，形成玻璃膜疣,。由于黃斑部結(jié) 構(gòu)與功能上的特殊性，此種改變更為明顯,。玻璃膜疣也見于正常視力的老年人,，但由此繼發(fā)的種種病理改變后,，則導(dǎo)致黃斑部變性發(fā)生,。本病大多發(fā)生于45歲以上，其患病率隨年齡增長而增高,，是當(dāng)前老年人致盲的重要疾病,。目前的一些治療手段只能延緩病情的進(jìn)展，無法最終治愈,。人類誘導(dǎo)多能干細(xì)胞(hiPS)的發(fā)現(xiàn)開辟了治療退化性疾病的新的治療途徑,，如治療AMD，通過移植人自身的干細(xì)胞以產(chǎn)生新的組織和細(xì)胞。
對于AMD疾病的移植可行性,，研究人員首次弄清楚了如何發(fā)揮hiPS的作用,，并使其擁有原視網(wǎng)膜色素上皮細(xì)胞(RPE)的特性。視網(wǎng)膜色素上皮細(xì)胞的死亡,，會導(dǎo)致AMD,。喬治敦大學(xué)科學(xué)家主持的該研究使得 AMD再生醫(yī)學(xué)方面獲得重要的突破。GUMC生物化學(xué)與分子細(xì)胞生物系助理教授,，該項(xiàng)研究的首席作者Nady Golestaneh博士說,，首次培育的hiPS-RPE細(xì)胞，已具備了RPE細(xì)胞的功能和特性,，可以成為治療AMD視網(wǎng)膜再生治療的重要選擇,。
Golestaneh及其同事采用已建立的實(shí)驗(yàn)室干細(xì)胞系，發(fā)現(xiàn)在特定環(huán)境下由hiPS培育的RPE,，在離子轉(zhuǎn)運(yùn),、膜電位、血管內(nèi)皮生長因子分泌以及基因表達(dá)模式方面與正常眼睛的RPE相類似,。然而,，我們也發(fā)現(xiàn)了一些問題。她解釋道,，來自于hiPS的RPE細(xì)胞呈現(xiàn)快速端?？s短，DNA的染色體損傷,，以及p21表達(dá)的提高引起細(xì)胞生長停滯,。這可能是由于iPS細(xì)胞重組過程中，皮膚成纖維細(xì)胞的基因中病毒的隨機(jī)整合,。因此,，無病毒iPS細(xì)胞的產(chǎn)生及其分化至RPE細(xì)胞成為這些細(xì)胞在臨床應(yīng)用上的必要步驟。
這項(xiàng)研究中將開始著重培育安全且可行的hiPS演化體細(xì)胞,?？偠灾@對于再生醫(yī)學(xué)的發(fā)展而言是重要的一步,。（生物谷Bioon.com）
英文鏈接：http://www.sciencedaily.com/releases/2011/03/110324103123.htm
再生泉鏈接：http://www.chinastemcell.org/newslast.asp?id=584
生物谷推薦英文摘要：
Stem Cells, 2011; DOI: 10.1002/stem.635
Human iPS-Derived Retinal Pigment Epithelium (RPE) Cells Exhibit Ion Transport, Membrane Potential, Polarized VEGF Secretion and Gene Expression Pattern Similar to Native RPE.
Maria Kokkinaki, Niaz Sahibzada, Nady Golestaneh.
Abstract
Aged-related macular degeneration (AMD) is one of the major causes of blindness in aging population and progresses with death of retinal pigment epithelium (RPE) and photoreceptor degeneration inducing impairment of central vision.
Discovery of human induced pluripotent stem (hiPS) cells has opened new avenues for the treatment of degenerative diseases using patient specific stem cells to generate tissues and cells for autologous cell-based therapy. Recently, RPE cells were generated from hiPS cells. However, there is no evidence that those hiPS-derived RPE possess specific RPE functions that fully distinguish them from other type of cells.
Here we show for the first time that RPE generated from hiPS under defined conditions exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression profile similar to those of native RPE. The hiPS-RPE could therefore be a very good candidate for RPE replacement therapy in AMD. However, these cells show rapid telomere shortening, DNA chromosomal damage and increased p21 expression that cause cell growth arrest. This rapid senescence might affect the survival of the transplanted cells in vivo and therefore, only the very early passages should be used for regeneration therapies. Future research needs to focus on the generation of “safe” as well as viable hiPS-derived somatic cells.
