科学家将正常细胞转变为胰岛素分泌细胞

科学家将正常细胞转变为胰岛素分泌细胞

WASHINGTON (Reuters) - Researchers have transformed ordinary cells into insulin-producing cells in a living mouse, improving symptoms of diabetes in a major step towards regenerative medicine.
华盛顿（路透社）— 研究者使正常细胞在小鼠活体内转化为胰岛素分泌细胞，这是再生医学在改善糖尿病症状方面迈出的一大步。

The technique, called direct reprogramming, bypasses the need for stem cells -- the body's master cells which, until now, have been indispensable to efforts to custom-make tissue and organ transplants.
这项技术被称为直接程序改编，它避开了对干细胞的依赖。到目前为止。在定向培养组织和器官移植方面，干细胞都是不可或缺的重要细胞。

The researchers used three genes carried by an ordinary virus to transform mouse exocrine cells, which make up about 95 percent of the pancreas, into the scarce insulin-producing beta cells that are destroyed in type 1 or juvenile diabetes.
研究者使用了三种基因，以普通病毒作为载体，用来将小鼠胰腺外分泌细胞转化为较为稀少的胰岛素合成beta细胞，前者占胰腺组成的95%，而后者在1型糖尿病和青少年糖尿病中往往已损毁。
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In theory, the same is possible using abundant human cells such as liver, skin or fat cells, Dr. Douglas Melton and colleagues at Harvard Medical School and Children's Hospital in Boston reported.
理论上，使用人体中较为丰富的细胞如肝细胞、皮肤细胞或脂肪细胞也可能获得相同的效果，来自波士顿哈佛医学院和儿童医院的Dr. Douglas Melton及其同事报道。

"It was easier than one might have thought," Melton, a Howard Hughes Medical Institute researcher and one of the world's top stem cell experts, said in a telephone interview.
“它比想象中容易，” Melton在一次电话采访中说，他是霍华德休斯医学研究所的研究员，世界一流干细胞专家之一。

"These cells are very stable and live for the life of the mouse."
“这些细胞相当稳定，在小鼠活体中工作正常。”

Scientists had been counting on stem cells to show them how to regenerate tissues and organs -- in the case of juvenile diabetes, to regenerate the pancreatic cells that are mistakenly destroyed by the body's immune system.
科学家曾对干细胞再生组织和器官寄予厚望，具体到青少年糖尿病，就是使被机体免疫系统错误损毁的胰腺细胞获得再生。

"I wake up every day thinking about how to make beta cells," said Melton, whose two children have type 1 diabetes.
“每天醒来我都在思考如何产生胰岛β细胞，” Melton说，他的两个孩子都患有1型糖尿病。

The most malleable and promising stem cells have been embryonic stem cells, taken from days-old embryos. But U.S. federal law strictly limits funding for such research and they are not easy to create.
最有希望和可行性的干细胞是胚胎干细胞，从数天大的胚胎获得的。但是美国联邦法严格限制对于该类研究的资金支持，同时该类细胞也不易培养。

CELL REPROGRAMMING
细胞程序改编

Last year, researchers discovered how to reprogram ordinary skin cells by taking them back to an embryonic-like state. These induced pluripotent stem cells can be used to study disease and might one day make tailor-made transplants.
去年，研究者发现了通过将正常皮肤细胞逆转至一种胚胎样状态使其得到重组的方法。这些诱导多能干细胞可以用于疾病研究，或许某天可以用于制备合适的移植物。

But now Melton and his team -- using knowledge gained from these earlier studies -- have skipped both steps.
但是现在Melton及其团队运用从早期研究中获得的知识跳过了这两步。

"What this shows is that you can go directly from one type of adult cell to another, without going back to the beginning," said Melton.
“从中我们可以看到，成人细胞可以直接从一种类型转到另一种类型，无须返回到初始状态，”Melton说。

Reporting in the journal Nature, the team said they did it in living mice, not in lab dishes.
研究团队在《自然》杂志上发表的报告中声称他们在活体小鼠上获得这一结果，而非在培养皿中。

They worked with diabetic mice that do not have the insulin-producing cells needed by the pancreas to help the body turn food into energy.
他们采用了没有胰岛素分泌细胞的糖尿病小鼠，而这种细胞在胰腺帮助机体将食物转化为能量的过程中是必需的。

Melton's team had to find which genes were needed to make cells function as the precious beta-cells. While every cell carries the full genetic code, only certain genes in any cell are working at any given time.
Melton 的研究队伍必须找出哪些基因可以使得细胞具有β细胞的功能。虽然每个细胞都携带有全部的遗传密码，但是在不同的细胞中只有特定的基因在特定的时间发挥作用。

The researchers had to find out which genes are "on" as an embryo grows its pancreas.
研究者必须找出在胚胎形成胰腺的过程中哪些基因是“开启”的。
Out of more than 1,000 genes, they found just three were needed -- Ngn3, Pdx1, and Mafa. Then an ordinary cold virus called an adenovirus carried these three genes into the digestive-juice-making exocrine cells of the pancreas.
在超过1000个基因中，他们只找到3个需要的—Ngn3, Pdx1, and Mafa。然后用一种普通的感冒病毒（称为腺病毒）将这三种基因转入胰腺的消化液分泌细胞。

This converted about 20 percent of the exocrine cells to beta cells that produced insulin, in turn lowering the soaring blood sugar levels in the mice.
这使得大约20%的外分泌细胞转化为合成胰岛素的β细胞，随后小鼠的高血糖水平得以降低。

The method might work first in people with severe type 2 diabetes, whose bodies no longer make insulin, Melton said.
这种方法也许会首先应用于严重的2型糖尿病患者，这些病人的机体不再产生胰岛素，Melton说。

"For type 1 diabetes we are still faced with the annoying problem of autoimmune attack," he said.
“对于1型糖尿病，我们仍然要面对自身免疫攻击这个难题，”他说。

Any transformed cells in type 1 diabetes would be destroyed by the same mistaken immune response that caused the disease in the first place.
在1型糖尿病上，任何转化细胞仍然会被引起这种疾病的错误免疫应答摧毁。

Before experiments begin in people, Melton wants to find a way to transform cells without using a virus. Using viruses to treat people, he noted, is risky and makes Food and Drug Administration experts nervous.
在应用于人类之前，Melton 想找到一种不使用病毒的细胞转化方法。 他指出，用病毒治疗人类疾病是有风险的，而且会使FDA感到不安。
(Editing by John O'Callaghan)