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.
