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台灣視網膜色素病變協會
:::左側區塊

First study using human embryonic stem cells for macular degeneration shows they are safe and lead t

發佈日期:2012/02/22 pm01:20:48

內容:
The Lancet today reports the use of human embryonic stem cells (hESC) to treat macular degeneration in human beings. It is the first report of the use of such cells in humans for any purpose. The study involved one elderly patient and one young patient with different forms of macular degeneration that had led to severe vision loss. The transplants appeared safe after four months, and both patients had some improvement in vision. The future therapeutic goal will be to treat patients earlier in the disease process, in order to boost the prospects of improving or retaining sight in new patients. The study is by Dr Robert Lanza, Chief Scientific Officer at Advanced Cell Technology, Marlborough, MA, USA, and Professor Steven Schwartz, Jules Stein Eye Institute Retina Division at the University of California, Los Angeles, CA, USA, and their colleagues.
Use of hESC is controversial for a number of reasons. There is an ongoing ethical debate surrounding whether or not embryonic stem cells should be used in treatments (on the basis that an embryo can be regarded as the earliest form of human life). There are also biological risks of use, including teratoma formation (a type of cancer that occurs when stem cells differentiate into multiple cell types and form incompatible tissues that can include teeth and hair). Cell reprogramming technologies are in development that will hopefully lead to rejection becoming a thing of the past. However, until then, so-called ‘immunoprivileged’ sites (that do not produce a strong immune response) such as the eye, will likely be the first parts of the human body to benefit from hESC transplants. It is the existence of the blood-ocular barrier in the eye that limits the immune response within the eye.
This study assessed transplantation of hESC-derived retinal pigment epithelium (RPE) into the subretinal space (under the retina of the eye) of one eye in two patients. One patient (female, in her 70s) had dry age-related macular degeneration (the leading cause of blindness in the developed world), and the other (female, in her 50s) had Stargardt’s macular dystrophy, the most common form of macular degeneration in young patients. 50,000 RPE cells were injected through a fine cannula into the subretinal space of each patient’s eye.
本研究評估人類胚胎幹細胞衍生的視網膜色素上皮(RPE)移植到視網膜的空間。一個病人(女性,在她70年代)有老年相關性黃斑病變(導致失明的主要原因),和其他(女性,在50歲時)有Stargardt的黃斑營養不良,最常見的黃斑病變發生在年輕患者。50000 RPE細胞注入到每個病人的眼睛內並由視網膜下腔細導管通過。 Patients received low-dose immunosuppression therapy, which doctors began to taper off after 6-weeks. After surgery, structural evidence confirmed cells had attached to Bruch’s membrane and survived throughout the study period. No safety concerns emerged in the four months post-transplant: no teratoma or other hyperproliferation were detected, and there were no signs of rejection or abnormal cell growth. The authors say that in patients who began with poor vision (both patients were legally blind), it is difficult to ascertain definite improvements in vision unless such improvements are spectacular. While neither patient lost vision, some standard tests suggested vision had improved in both. The patient with Stargardt’s disease went from being able to only see hand movements at first, to being able to see single finger movements, through to 20/800 vision.
Using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, the patient went from being unable to read any letters to being able to read five letters. In the patient with dry age-related macular degeneration, the improvement was from being able to read 21 letters on this chart pre-treatment up to a peak of 33 after 2 weeks, before settling at a stable reading level of 28 letters.

The authors conclude: “Our study is designed to test the safety and tolerability of hESC-RPE in patients with advanced-stage Stargardt’s macular dystrophy and dry age-related macular degeneration. So far, the cells seem to have transplanted into both patients without abnormal proliferation, teratoma formation, graft rejection, or other untoward pathological reactions or safety signals. Continued follow-up and further study is needed. The ultimate therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue.”
Dr Lanza adds: “It has been over a decade since the discovery of human embryonic stem cells. This is the first report of hESC-derived cells ever transplanted into patients, and the safety and engraftment data to-date looks very encouraging. Although several new drugs are available for the treatment of the wet type of AMD, no proven treatments currently exist for either dry-AMD or Stargardt’s disease. Despite the progressive nature of these conditions, the vision of both patients
appears to have improved after transplantation of the cells, even at the lowest dosage. This is particularly important, since the ultimate goal of this therapy will be to treat patients earlier in the course of the disease where more significant results might potentially be expected.”
“ Professor Anthony Atala, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, NC, USA, commented, “The potential to use human embryonic derived cells with a therapeutic effect in patients is now finally realised... The ultimate therapeutic goal for patients with visual loss would be to treat them earlier in the disease processes, hopefully increasing the likelihood of visual rescue. Much remains to be seen- literally.


中文簡述:人類胚胎幹細胞(胚胎幹細胞)的使用在人類治療黃斑部病變。這是人類使用這種細胞的第一次報告。參與這項研究的老年患者和一個年輕的病人,因為黃斑部病變導致嚴重的視力喪失。移植4個月後仍非常安全,兩個病人的視力有所改善。未來的治療目標將是盡早治療患者,以促進改善或保留患者視力。這項研究是由馬爾堡,先進細胞技術公司首席科學家Robert Lanza博士和Steven Schwartz教授、Jules Stein眼科研究所在美國加州大學洛杉磯分校,美國加利福尼亞州,和他們視網膜科的同事。
人類胚胎幹細胞的使用有許多爭議。其中之一就是是否可以應用於治療(在此基礎上,胚胎可算是最早的人類生活形式)的倫理爭論。也有風險,使用生物,包括形成畸胎瘤(一種癌症的類型,發生時,幹細胞分化成多種細胞類型,並形成的不相容組織,可以包括牙齒和頭髮)。細胞重編程技術的發展,希望能引起排斥成為過去的事情。然而,在那之前,所以所謂“immunoprivileged”的網站,如眼睛(不產生強烈的免疫反應),將有可能是人體的第一部分,從人類胚胎幹細胞移植中獲益。這是限制了眼內的免疫反應中的眼睛,導致血眼屏障的存在。
患者接受低劑量的免疫抑制治療,6週後,醫生開始逐漸減弱。手術後,細胞附著布魯赫的膜結構的證據證實,並在整個研究期間倖存下來。在移植後4個月沒有安全問題出現,沒有畸胎瘤或其他增生的檢測,並且異常細胞的生長沒有任何跡象。
作者說,患者視力不良(兩個患者眼盲)開始,這是難以有效的改善視力。雖然沒有病人失去了視力,一些標準的測試表明,既改善視力。Stargardt病的病人從起初只能看到手部動作,可以看到單手指的動作,提高了20/800的視覺。
作者總結說:“我們的研究旨在測試中晚期黃斑營養不良和年齡相關性黃斑病變患者的胚胎幹細胞的視網膜色素上皮的安全性和耐受性。到目前為止,似乎已經移植到兩個病人細胞無異常增殖,無畸胎瘤的形成,無移植排斥反應,或其他不良的病理反應或安全信號。進一步研究是必要的。治療的最終目標,是要及早治療患者的疾病過程中,可增加了感光和治療視覺的可能性。“

使用早期治療糖尿病視網膜病變研究(ETDRS)視力表,病人就無法讀取任何能夠讀取五個字母的字母。在和年齡相關性黃斑病變的患者,改善後能夠穩定的閱讀水平的28個字母,讀這個圖表治療2週後,可以閱讀33峰21字母。蘭扎博士補充說:“它已經超過了十年以來的人類胚胎幹細胞的發現。這是人類胚胎幹細胞衍生的細胞移植到患者有史以來的第一次報告,以及最新的安全性和移植數據看起來非常令人鼓舞的。雖然一些新的藥物可用於治療濕型AMD的,沒有有效的治療能夠醫治AMD或Stargardt病。這兩個病人的視力似乎有所改善細胞移植後,即使在最低的劑量。這一點尤為重要,因為這種療法的最終目標是要及早治療病人的潛在預期更為顯著的結果可能疾病的過程中。

威克森林再生醫學研究所,喚醒醫學院,美國北卡羅來納州,森林小學教授Anthony Atala,評論說,“潛在的使用人類胚胎細胞在患者的治療效果,現在終於實現了...... 最終的治療目標是使喪失視力的患者,在疾病過程中,增加恢復視覺的的可能性。但仍有許多需要努力。