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【Science】将瘢痕组织变成一颗跳动的心脏

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Turning Scar Tissue Into a Beating Heart

Cell biologists often seem like modern-day alchemists. Instead of turning lead or straw into gold, they're looking for ways to turn one kind of cell into another, potentially more useful, cell. Now, one research team has found a way to turn a very common heart cell into a cell missing in injured hearts.

A healthy heart is a mix of several kinds of cells, including cardiomyocytes, the muscle cells that beat, and cardiac fibroblasts, which provide structural support and help keep all the heart cells working together. When a mammalian heart is injured, for example by a heart attack, it forms scar tissue dominated by fibroblasts instead of cardiomyocytes. As a result, the heart doesn't fully recover its pumping capacity. Developmental biologist Deepak Srivastava and cardiovascular researcher Masaki Ieda of the Gladstone Institute of Cardiovascular Disease in San Francisco, California, and their colleagues wondered whether some cellular alchemy could prompt the fibroblasts to turn into cardiomyocytes.

The researchers used a technique called cellular reprogramming, which others had shown can turn one cell type into another. They inserted into mouse cardiac fibroblasts extra copies of more than a dozen genes known to play a role in heart development and watched to see whether any of the cells took on characteristics of cardiomyocytes. After several rounds of tests, the scientists identified a trio of genes that together did the trick. The team inserted extra copies of the three genes into cardiac fibroblasts growing in the lab, and after 2 weeks about 20% of them took on characteristics of cardiomyocytes, expressing typical genes for the muscle cells. After growing for a month, the reprogrammed cells began to contract, like beating heart cells, the researchers report in the 6 August issue of Cell. The reprogrammed cells look and act convincingly like bona fide cardiomyocytes, says Christine Mummery, a developmental biologist not involved with the research who studies cardiac stem cells at Leiden University Medical Center in the Netherlands.

Whether these cells could actually help repair a damaged heart remains an open question, however. Transplants of heart muscle cells created from embryonic stem cells haven't worked as hoped so far—the new cells don't seem to fully integrate into the heart tissue. Ideally, Srivastava says, researchers will find small molecules that can replace the three-gene cocktail. Such molecules could be applied directly to an injured heart and turn fibroblasts into cardiomyocytes. That might lead to more effective repair, he suggests. Mummery agrees. Reprogramming cells directly in the heart "would be potentially much more interesting" than transplantation, she says. The most important question now, she says, is whether the same alchemy will work on human heart cells.

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2010-08-08 13:52 浏览 : 773 回复 : 3

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• # 妇儿联动 # 启动期，作为妇产科/儿科医生，你有哪些问题，想请教对方？

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2010-08-08 13:53

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• 一图解读｜血常规化验单

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Cell biologists often seem like modern-day alchemists. Instead of turning lead or straw into gold, they're looking for ways to turn one kind of cell into another, potentially more useful, cell. Now, one research team has found a way to turn a very common heart cell into a cell missing in injured hearts.

细胞生物学家更像现代版的炼金术师。虽然不是点石成金，他们正寻找方法使某种类型的细胞变成另外一种可能更有用途的细胞。现在一个研究小组已经发现一种方法将将非常普通的心脏细胞变成受损心脏所缺少的细胞。

A healthy heart is a mix of several kinds of cells, including cardiomyocytes, the muscle cells that beat, and cardiac fibroblasts, which provide structural support and help keep all the heart cells working together. When a mammalian heart is injured, for example by a heart attack, it forms scar tissue dominated by fibroblasts instead of cardiomyocytes. As a result, the heart doesn't fully recover its pumping capacity. Developmental biologist Deepak Srivastava and cardiovascular researcher Masaki Ieda of the Gladstone Institute of Cardiovascular Disease in San Francisco, California, and their colleagues wondered whether some cellular alchemy could prompt the fibroblasts to turn into cardiomyocytes.

一个健康的心脏是不同类型细胞的混合体，包括心肌细胞 -- 负责搏动的肌细胞，和心脏成纤维细胞 -- 提供构架支持和保证所有心脏细胞一起工作。当哺乳动物的心脏受损时，例如遭受一次心脏病，它会形成成纤维细胞的瘢痕组织替代心肌细胞。结果，心脏无法完全恢复它的搏动能力。发育生物学家Deepak Srivastava和加州旧金山Gladstone心血管病研究所心血管研究员Masaki Ieda以及他们的同事在想是否某种细胞炼金术能够将成纤维细胞变成心肌细胞。

The researchers used a technique called cellular reprogramming, which others had shown can turn one cell type into another. They inserted into mouse cardiac fibroblasts extra copies of more than a dozen genes known to play a role in heart development and watched to see whether any of the cells took on characteristics of cardiomyocytes. After several rounds of tests, the scientists identified a trio of genes that together did the trick. The team inserted extra copies of the three genes into cardiac fibroblasts growing in the lab, and after 2 weeks about 20% of them took on characteristics of cardiomyocytes, expressing typical genes for the muscle cells. After growing for a month, the reprogrammed cells began to contract, like beating heart cells, the researchers report in the 6 August issue of Cell.The reprogrammed cells look and act convincingly like bona fide cardiomyocytes, says Christine Mummery, a developmental biologist not involved with the research who studies cardiac stem cells at Leiden University Medical Center in the Netherlands.

研究者使用一种细胞重新编程的技术，是一种细胞转变为另一种。他们在鼠心脏成纤维细胞中插入十多种基因的更多拷贝，这些基因在心脏发育中起着重要的作用。然后观察时候某些细胞出现的心肌细胞的特征。在几轮实验之后，科学家们发现了三个基因，可以协同完成这种变化。研究小组将三种基因的额外拷贝插入实验室培养的心脏成纤维细胞，两周后，大约20%的细胞开始具有心肌细胞的特征，表达肌细胞特有的基因。生长一个月之后，重新编程的细胞开始收缩，如同搏动的心脏细胞，研究者在8月6日的细胞杂志中报道。荷兰Leiden大学医学中心心脏干细胞研究的发育生物学家Christine Mummery并未参与此项研究，她说，重编程的细胞形状和行为毫无疑问如同真的心肌细胞。

Whether these cells could actually help repair a damaged heart remains an open question, however. Transplants of heart muscle cells created from embryonic stem cells haven't worked as hoped so far—the new cells don't seem to fully integrate into the heart tissue. Ideally, Srivastava says, researchers will find small molecules that can replace the three-gene cocktail. Such molecules could be applied directly to an injured heart and turn fibroblasts into cardiomyocytes. That might lead to more effective repair, he suggests. Mummery agrees. Reprogramming cells directly in the heart "would be potentially much more interesting" than transplantation, she says. The most important question now, she says, is whether the same alchemy will work on human heart cells.

但是这些细胞是否可以帮助修复受损的心脏依然是一个未解决的问题。目前干细胞生成的心肌细胞移植并没有预期那么成功 - 新的细胞看起来无法完全整合进入心脏组织。Srivastava说，理想来讲，研究者将发现一些小分子去代替三基因混合方法。这样的小分子和直接作用于一个受损的心脏将成纤维细胞变成心肌细胞。那样的情况将带来更有效的治疗，他建议。 Mummery 也同意这样的建议。她说，在心脏中直接重新编程细胞比移植更令人关注。现在最重要的问题是同样的炼金术是否可以作用于人类的心脏细胞。

2010-08-09 00:47

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HAKUTA 编辑于 2010-08-09 10:09

• 广东省人民医院一胸外科80后医生猝死

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细胞生物学家更像现代版的炼金术师。虽然不是点石成金，他们正寻找方法使某种类型的细胞变成另外一种可能更有用途的细胞。现在一个研究小组已经发现一种方法将将非常普通的心脏细胞变成受损心脏所缺少的细胞。

一个健康的心脏是不同类型细胞的混合体，包括心肌细胞 -- 负责搏动的肌细胞，和心脏成纤维细胞 -- 提供构架支持和保证所有心脏细胞一起工作。当哺乳动物的心脏受损时，例如遭受一次心脏病，它会形成成纤维细胞的瘢痕组织替代心肌细胞。结果，心脏无法完全恢复它的搏动能力。发育生物学家Deepak Srivastava和加州旧金山Gladstone心血管病研究所心血管研究员Masaki Ieda以及他们的同事在想是否某种细胞炼金术能够将成纤维细胞变成心肌细胞。

研究者使用一种细胞重新编程的技术，是一种细胞转变为另一种。他们在鼠心脏成纤维细胞中插入十多种基因的更多拷贝，这些基因在心脏发育中起着重要的作用。然后观察时候某些细胞出现的心肌细胞的特征。在几轮实验之后，科学家们发现了三个基因，可以协同完成这种变化。研究小组将三种基因的额外拷贝插入实验室培养的心脏成纤维细胞，两周后，大约20%的细胞开始具有心肌细胞的特征，表达肌细胞特有的基因。生长一个月之后，重新编程的细胞开始收缩，如同搏动的心脏细胞，研究者在8月6日的细胞杂志中报道。荷兰Leiden大学医学中心心脏干细胞研究的发育生物学家Christine Mummery并未参与此项研究，她说，重编程的细胞形状和行为毫无疑问如同真的心肌细胞。

但是这些细胞是否可以帮助修复受损的心脏依然是一个未解决的问题。目前干细胞生成的心肌细胞移植并没有预期那么成功 - 新的细胞看起来无法完全整合进入心脏组织。Srivastava说，理想来讲，研究者将发现一些小分子去代替三基因混合方法。这样的小分子和直接作用于一个受损的心脏将成纤维细胞变成心肌细胞。那样的情况将带来更有效的治疗，他建议。 Mummery 也同意这样的建议。她说，在心脏中直接重新编程细胞比移植更令人关注。现在最重要的问题是同样的炼金术是否可以作用于人类的心脏细胞。

2010-08-09 10:10

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• 首套【肺石医生】表情上架啦，一起斗图吧！

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