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Monday, April 17, 2017

(商業化異體iPS細胞庫) 日本 人種單純 異體iPS移植成功首例


陳耀昌:再生移植醫學新紀元 2017/04/16 出處:財訊雙週刊第526  作者:陳耀昌 安倍首相稱生醫研究產業為「日本經濟復甦的第三支箭」,放寬法規、預算的大力支持,其他生醫學者紛紛抱怨,所有研究經費都挹注到iPS去了。329日一早看到「日本完成世界首例iPS細胞他體移植」的新聞,於是決定放棄已寫好的專欄文章,因為這件事太重要了。由幹細胞分化再生,再加上「他體」移植,所以我稱為「再生移植醫學」。

日本他體iPS幹細胞移植 全人類皆受惠 我立刻上臉書強調這件事的重要及意義:日本之醫療產業未來成敗,在此一舉。一、1億元費用變成十分之一,(iPS進入產業化不是夢了!二、要觀察兩年,確定無慢性排斥,才算成功。三、祕訣在如何選擇低排斥細胞?我想是HLA人類白血球抗原)半套haploidentical(單倍型)相符吧。對日本而言,這攸關產業成敗,國力興衰。而對全人類來說,這是再生移植醫學的新紀元,影響全人類福祉。我也有感慨,「山中伸彌簡直以一人身負日本興衰之重任!」今年116日,《紐約時報》刊登一篇對山中伸彌的專訪,標題是「幹細胞革命即將來臨─慢慢地」。這個革命就是「iPS的運用,將由自體改為異體(日本稱為他體)」。沒想到山中的腳步真快,才70天不到,並不是「慢慢地」,日本人就完成了世界第一例。「iPS細胞」已經變成一個不須再解釋的名詞。這是2007年山中發表的驚世研究。他將已成熟分化的皮膚細胞轉變為無所不能的幹細胞。此項研究一發表,大家就預測他會得諾貝爾獎,果然一二年就成真,山中成為最快得獎的科學家。簡單說,iPS細胞就是「不需要胚胎的胚胎幹細胞」,而且人人身上取之不盡、用之不竭。於是日本傾全力發展iPS臨床運用,安倍首相稱生醫研究產業為「日本經濟復甦的第三支箭」,放寬法規、預算的大力支持,重點就是iPS而衍生的再生醫學,有了iPS,器官再造將不再是神話。其他生醫學者紛紛抱怨,所有研究經費都挹注到iPS去了。我的一位從事造血幹細胞研究的朋友尖酸地說:「iPS幹細胞,那也是一種癌症幹細胞!」是的,iPS的罩門就是「癌化的威脅」一四年,神戶理化學研究所的高橋政代醫師就完成了世界第一例自體iPS網膜幹細胞移植,成功治療一位黃斑退化病變的女病人。山中伸彌的團隊將病人的體細胞轉換成iPS幹細胞,然後培養成視網膜錐形細胞,移植後迄今已經二年多。

解決兩大痛點 iPS幹細胞革命大躍進 而在一五年,高橋政代準備進行第二例自體iPS視網細胞移植時,細胞株DNA的定序發現有突變,於是臨時叫停。雖然一六年夏天,團隊又獲得繼續進行的許可,但是山中及高橋心已不在此。他們的雄心更大,希望直接解決自體iPS的兩大缺點:一、自體移植的細胞培養甚為匆促,萬一像這樣遇到不可測的突變,匆匆叫停,非常麻煩。二、自體移植是客製化的一對一治療,非常昂貴。例如第一例,準備過程11個月,耗費上億日圓,也就是3000萬元台幣,這樣的價格,只限於學術研究而無法真正推廣,也就是無法產業化。於是山中及高橋決定做「他體」移植,也就是我們說的「異體」,這就是山中伸彌在《紐時》報導所提的「幹細胞革命」。若能成功,成本可以減少到十分之一,也就是1000萬日圓,300萬元台幣,那時產業化及國民治療運用就不是夢了!用「他體」或「異體」,成敗關鍵在於是否能處理或避免「排斥」。就如這次日本團隊說,要觀察兩個月方能確知無慢性排斥。而山中在《紐時》報導中說,他們可以選擇「低排斥細胞株」。我猜測就是選擇HLA半套符合的正常人細胞株來做移植。九六年,台灣的骨髓庫有10萬捐贈者,台灣民眾找到相符合HLA的機率不到50%而那時日本的骨髓庫只有6萬,卻有75%的民眾可以找到HLA符合捐髓者。日本人HLA的同質性,幾乎是世界最高,因為日本的人種非常單純,很少與外來種族混血。也因此日本的異體臍帶血幹細胞移植,屬全球最成功,遙遙領先,所以也最省錢。山中向《紐時》記者說,他估計只要有一百株iPS幹細胞株就可以供日本全國使用。這是日本人的獨特優勢。日本人這項醫學創舉,我們拭目以待,樂觀其成。而日本人的iPS幹細胞庫、臍帶血幹細胞庫所帶來的成果,以及他們研議中的間質幹細胞庫,在在證明這些幹細胞庫是國家寶貴資產,攸關國民健康福祉,在戰爭或意外災難時,甚至提升為國安層次。台灣也應該建立國人的各種幹細胞庫,其理甚明,希望政府能盡速規畫及踏出第一步。

World's First Reprogrammed Stem Cell Implemented on Japanese Man Joseph Young April 3, 2017 Researchers successfully implemented reprogrammed induced pluripotent stem cells (iPS) with the use of an anonymous donor. IPS cells are significantly different from conventional stem cells in the sense that they are derived from mature cells of an individual. The process of retrieving and developing iPS cells starts with the extraction of mature cells from the subject. These cells are readily available in most parts of the human body, including the skin. When mature cells are extracted, researchers reprogram these cells to an embryonic state, turning it into a stem cell. This reprogramming process enables researchers to then use the iPS cells to treat diseases in other parts of the body. On March 28, a Japanese man from the Hyogo prefecture of Japan recovered from an age-related macular degeneration after receiving reprogrammed iPS cells extracted from the skin of an anonymous donor. The cells were transplanted onto the retina of the patient to prevent his disease from leading to permanent blindness or other serious long-term illnesses. The procedure was completed at the Kobe City Medical Center General Hospital, by surgeon Yasuo Kurimoto, who oversaw the entire process of extracting, reprogramming and transplanting iPS cells. The successful transplant of iPS cells on the patient suffering with age-related macular degeneration convinced the Japan's health ministry to approve five additional patients to undergo the same procedure to treat potentially severe diseases. According to various reports, the Kobe City Medical Center General Hospital led a similar procedure back in 2014 when surgeon Kurimoto helped a Japanese woman receive retinal tissue developed from stem cells extracted from the patient's own iPS cell. At the time, Kurimoto extracted mature cells from the patient's skin and used those cells to develop iPS cells and next-generation stem cells. The difference between the 2014 and 2017 study is that the latter relied on the mature cells of an anonymous donor. The recent study of Kurimoto proved that mature cells from donors can be utilized to help patients to prevent or recover from serious diseases that weren't possible to treat prior to the use of iPS cells. In addition to the on-going study of Kurimoto, Shinya Yamanaka, a Nobel-prizewinning stem-cell scientist from the Kyoto University, is currently developing an iPS cell bank which can be applied to and adopted by around 30 to 50 percent of Japan's population. Using the same method of reprogramming mature cells, Yamanaka is planning to establish a cell bank that can be utilized commercially by surgeons across the country to prevent diseases and restore lost function by March of 2018. Although Yamanaka's iPS Cell Stock for Regenerative Medicine is based on the cell lines from a single donor as of now, in the next few years, Yamanaka and his team plan on securing HLA cell lines from up to 10 donors to match the majority of the Japanese population.

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