幹細胞論壇

中央大學材料化學系日籍教授樋口亜紺與國泰臨床醫學研究中心主任凌慶東等人共同合作,利用四個基因-Oct4, Sox2, Klf4, c-Myc,成功的將纖維母細胞轉型成如同胚胎幹細胞,也有高度分化能力的誘導式多功能幹細胞.
這項發現與2007年日本Yamanaka教授首次利用的四個基因轉型是相同的,差別在於台灣的研究人員利用新的技術,讓成熟細胞的細胞膜張開,直接放入四個基因於其中.這樣的做法有別於傳統的病毒法,基因可以無限次地被導入,並可減少細胞感染和突變的機會.
雖然這個方法的成功率只有0.3-1%,也就是1000細胞只有3到10顆能轉型成功,但這個新的突破和發現已先刊登在《化學評論》（Chemical Review）期刊網路版中,未來仍有許多進步空間.
http://pubs.acs.org/doi/abs/10.1021/cr1003612?prevSearch=%255Btitle%253A%2Binduced%2Bpluripotent%2Bstem%2Bcells%255D%2BNOT%2B%255Batype%253A%2Bad%255D%2BNOT%2B%255Batype%253A%2Bacs-toc%255D&searchHistoryKey=

港大研究團隊最近成功在不須使用動物生物成分的情況下，製造出誘導式多功能幹細胞，這種新的誘導式多功能幹細胞和胚胎幹細胞一樣，可轉化成為不同的組織的細胞，包括心臟、腦、血管、肝等，研究結果已刊登於科學期刊《Cellular Reprogramming》。 
負責這次研究的香港大學李嘉誠醫學院研究人員(左起)：內科學系高級技術主任黎永漢先生、內科學系臨床助理教授蕭頌華醫生、內科學系心臟學科謝鴻發教授及內科學系及眼科研究所助理教授連祺周博士

美國俄亥俄州的兒童醫院(Cincinnati Children hospital)日前利用誘導式多功能幹細胞(iPSC),取代胚胎細胞,第一次成功的分化成小腸細胞.這項研究已在12日發表在自然(nature)期刊中.
科學家利用iPSC誘導成小腸細胞
iPSC如同胚胎細胞,就有高度分化能力,可分化身體三個胚層的組織.科學家利用化學和蛋白質的生長因子,促使iPSC只分化出內胚層組織.內胚層組織包含體內的器官組織,像是食道、胃、小腸、胰臟、肺臟和肝臟.

（中央社華盛頓8日法新電）美國科學家首創以幹細胞技術從2隻雄性老鼠身上孕育出幼鼠，科學家表示這項新突破可幫助保育瀕臨絕種的動植物，甚至有一天能幫助人類同性情侶擁有自己血緣基因的孩子。
據今天刊載於生殖科學期刊（journal Biology of Reproduction）的研究表示，德州再生科學家成功操控雄性（XY染色體）老鼠胚胎細胞，發展出「誘發性多功能性幹細胞」（induced pluripotent stem cells,iPS）細胞株。
這些「誘發性多功能性幹細胞」就是所謂已接受過基因重編，以便成為類胚胎幹細胞狀態的成人細胞。
部分從新細胞株成長出來的細胞會直接失去Y染色體，成為XO細胞。
這些XO細胞注入到雌性老鼠胚胎並移植到代理孕鼠體內後，就會生下帶有原先雄性老鼠X染色體的幼鼠。
這些幼鼠長大與正常的雄性鼠交配後，生下的幼鼠無論雄性或雌性，都帶有有原先2位鼠爸爸的基因。
這份研究是由美國德州大學的癌症治療中心（MD Anderson Cancer Center）研究員所執行。

1998科學家利用體外授精技術獲得胚胎幹細胞,2007日本Yamanaka教授利用皮膚細胞成功誘導回胚胎幹細胞,2010科學家再創新,繞過幹細胞的過程,直接利用體細胞轉型為另一個組織的前驅細胞.

將體細胞加入四個基因轉型成類似胚胎幹細胞,稱為誘導式多功能幹細胞(iPSC),開啟兩階段式細胞分化與器官修補工程.但發展至今,科學家發現iPSC的誘導過程需較長的時間,又易演變成癌細胞.後續分化成的體細胞也較不精確與成熟,整個生物工程相對比較困難又無效率.因此科學家發明[直接轉型技術](Direct Conversion),將一個體細胞轉型為需要修補組織的體細胞,繞過幹細胞的中間步驟.
從2008年開始,科學家利用小鼠模式成功將一種胰臟細胞轉型為另一種胰臟細胞.後續也有將皮膚細胞直接轉型為神經,心肌和血液細胞等研究.
每個人身體的細胞都帶有相同的基因,但是在分化過程中細胞會啟動不同的基因來表現,所以產生不同組織的體細胞.[直接轉型技術](Direct Conversion)就是植入啟動特定基因表現的訊息蛋白,使原本的細胞因表現特定基因而轉型成另一種體細胞.
這項發明技術仍面臨許多問題,像是轉型的細胞是否是正常?細胞是否可維持?技術是否穩定可靠?相信再過幾年,科學家會一一克服這些問題的所在.
 
Scientists trick cells into switching identities
Scientists are reporting early success at transforming one kind of specialized cell into another, a feat of biological alchemy that doctors may someday perform inside a patient's body to restore health.
So if a heart attack damages muscle tissue in the heart, for example, doctors may someday be able to get other cells in that organ to become muscle to help the heart pump.
That's a futuristic idea, but researchers are enthusiastic about the potential for the new direct-conversion approach.
"I think everyone believes this is really the future of so-called stem-cell biology," says John Gearhart of the University of Pennsylvania, one of many researchers pursuing this approach.
The concept is two steps beyond the familiar story of embryonic stem cells, versatile entities that can be coaxed to become cells of all types, like brain and blood. Scientists are learning to guide those transformations, which someday may provide transplant tissue for treating diseases like Parkinson's or diabetes.
It's still experimental. But at its root, it's really just harnessing and speeding up what happens in nature: a versatile but immature cell matures into a more specialized one.
The first step beyond that came in 2007, when researchers reversed the process. They got skin cells to revert to a state resembling embryonic stem cells. That opened the door to a two-part strategy: turn skin cells from a person into stem cells in the lab, and then run the clock forward to get whatever specialized cell you want for transplant.
The new direct-conversion approach avoids embryonic stem cells and the whole notion of returning to an early state. Why not just go directly from one specialized cell to another? It's like flying direct rather than scheduling a stopover.
Even short of researchers' dreams of fixing internal organs from within, Gearhart says direct conversion may offer some other advantages over more established ways of producing specialized cells. Using embryonic stem cells is proving to be inefficient and more difficult than expected, scientists say. For example, the heart muscle cells developed from them aren't fully mature, Gearhart noted.
And there's no satisfactory way yet to make mature insulin-producing cells of the pancreas, which might be useful for treating diabetes, says George Daley of Children's Hospital Boston and the Harvard Stem Cell Institute.
So direct conversion might offer a more efficient and faster way of getting the kinds of cells scientists want.
A glimpse of what might be possible through direct conversion emerged in 2008. Researchers got one kind of pancreatic cell to turn into another kind within living mice.
But far more dramatic changes have been reported in the past year in lab dishes, with scientists converting mouse skin cells into nerve cells and heart muscle cells. And just this month came success with human cells, turning skin cells into early stage blood cells.
The secret to these transformations is the fact that all cells of a person's body carry the same DNA code. But not all the genes are active at any one time. In fact, a cell's identity depends on its lineup of active genes. So, to convert a cell, scientists alter that combination by inserting chemical signals to activate particular genes.
"This is something that's really caught fire because it's an easy strategy to use," Gearhart said. "Everyone's out there trying their different combinations (of chemical signals) to see if they can succeed."
But success is not so easy. "There's a lot of experiments failing," Daley said. "A lot of people are just taking a trial-and-error approach, and that's fundamentally inefficient. And yet, it may create a breakthrough."
Even when the experiments work, there are plenty of questions to answer. Can this technique reliably produce transformed cells? Are these new cells normal? Or do they retain some hidden vestiges of their original identity that might cause trouble later on?
"When we make a duck look like a cat, it may look like a cat and meow, but whether it still has feathers is an issue," Daley said.
And ultimately: Would it be safe to transplant these cells into patients?
"We're a long way from showing safety and efficacy for any of these things," Gearhart said. "This stuff is all so new that we have a lot of work to do."
In any case, he and Daley said, scientists will still work with embryonic stem cells and the man-made versions first produced in 2007, called iPS cells. Those technologies clearly have places in various kinds of research, and it's not yet clear whether they or direct conversion will eventually prove best for manufacturing replacement cells for people.

      新華網東京11月23日電（記者藍建中）日本東京大學的研究人員宣布，他們開發出了用誘導多功能幹細胞（iPSC細胞）製造血小板的技術，並通過動物實驗確認了制造出來的血小板具有止血功能。
　　iPSC細胞是具有較強分化潛力的幹細胞，由皮膚細胞等體細胞經基因改造“誘導”發育而成。培養這類細胞不需要利用人類早期胚胎，而且可以無限增殖，因此新技術有望用於大量生產輸血用的血小板。
　　東京大學副教授江藤浩之率領的研究小組，在22日的美國《實驗醫學雜誌》月刊上發表論文說，他們首先利用人體皮膚纖維組織母細胞和臍帶血細胞制造出iPSC細胞，然後加入幾種血液細胞增殖因子和營養細胞，培養出能夠制造血小板的巨核細胞，最終制造出血小板。
　　研究人員將制造出的血小板輸給小鼠，發現血小板集中到受傷的血管上，形成血栓，正常發揮了血小板的功能。

美國的生物研究沙克中心和加州聖地牙哥分校的團隊研究日前成功的從瑞特氏症(Rett syndorme)病人身上的皮膚細胞,誘導成多功能幹細胞(iPSC),再分化成自閉症(Autism)病人的神經細胞,如此可以研究造成病患神經細胞缺陷的致病機轉.
科學家藉由此方法發現,自閉症病人的腦神經細胞發生神經傳導的缺失,其突觸(synape)和樹突細胞(dentrite spine)漸漸減少,但其缺失是可逆的反應,因此燃起科學家的希望,認為自閉症是可以治療的疾病.此研究已發表在2010.11.12 的[細胞] (CELL) 期刊中.
蕾特氏症(Rett syndrome)是泛自閉症障礙(Autism spectrum disorders)最常見的一種神經系統的疾病，與基因異常(MeCP2 gene)有關。好發生於女孩，6-18個月時發展正常，18個月以後漸漸會出現病症，中後期會有發展遲滯，語言和智能上的障礙。
過去科學家只能利用電腦斷層掃描或是切片組織來研究自閉症的腦神經缺陷,如今能在實驗室中利用病患的多功能幹細胞衍生的神經細胞,更確切的得知自閉症障礙的病理機轉.

 
波士頓大學再生醫學和呼吸系統中心的研究團隊成功地從囊性纖維化和肺水腫病患的皮膚細胞,加入重組載體(stem cell cassette; STEMCCA) 誘導成100株系的多功能幹細胞(iPSC),此項研究已刊登在目前的[幹細胞]期刊 (Stem Cell).科學家希望這些幹細胞能進一部治療病患本身的肺臟疾病.

 
   

    2010年10月1日 星期五 09:57

（路透華盛頓30日電）研究人員已發現意外迅速且明顯安全的方式，把普通皮膚細胞轉變為幹細胞和肌肉細胞。

他們說，這種方式可望為再生醫學這種新領域提供生成皮膚的新方式，醫師期望最終能修復受傷部位，甚至替換器官。

哈佛醫學院的羅西（Derrick Rossi）在期刊Cell Stem Cell中說，他們正努力發現新方法生成多能幹細胞。

只需要3或4個基因就能讓皮膚細胞等普通細胞時光倒轉，發揮幹細胞功能。現行方式採用病毒攜帶新基因進入細胞，可能導致腫瘤等問題。）

http://hk.news.yahoo.com/article/101001/21/khsm.html