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World first: Chinese scientists create pig stem cells
5 K+ g! m  H& r$ }# H: vDiscovery has far-reaching implications for animal and human health
  i7 A) d5 q& oThis release is available in Chinese.
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- N$ G2 Z) \1 m/ OScientists have managed to induce cells from pigs to transform into pluripotent stem cells – cells that, like embryonic stem cells, are capable of developing into any type of cell in the body. It is the first time in the world that this has been achieved using somatic cells (cells that are not sperm or egg cells) from any animal with hooves (known as ungulates). - n: b$ M0 {( R4 T- u( A

" K% z2 d8 M3 u5 |* m  GThe implications of this achievement are far-reaching; the research could open the way to creating models for human genetic diseases, genetically engineering animals for organ transplants for humans, and for developing pigs that are resistant to diseases such as swine flu.
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1 Z3 v4 L1 f2 XThe work is the first research paper to be published online today (Wednesday 3 June) in the newly launched Journal of Molecular Cell Biology [1].
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Dr Lei Xiao, who led the research, said: "To date, many efforts have been made to establish ungulate pluripotent embryonic stem cells from early embryos without success. This is the first report in the world of the creation of domesticated ungulate pluripotent stem cells. Therefore, it is entirely new, very important and has a number of applications for both human and animal health."8 \! ?, s! a- C' G$ n9 ]
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Dr Xiao, who heads the stem cell lab at the Shanghai Institute of Biochemistry and Cell Biology (Shanghai, China), and colleagues succeeded in generating induced pluripotent stem cells by using transcription factors to reprogramme cells taken from a pig's ear and bone marrow. After the cocktail of reprogramming factors had been introduced into the cells via a virus, the cells changed and developed in the laboratory into colonies of embryonic-like stem cells. Further tests confirmed that they were, in fact, stem cells capable of differentiating into the cell types that make up the three layers in an embryo – endoderm, mesoderm and ectoderm – a quality that all embryonic stem cells have. The information gained from successfully inducing pluripotent stem cells (iPS cells) means that it will be much easier for researchers to go on to develop embryonic stem cells (ES cells) that originate from pig or other ungulate embryos.
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Dr Xiao said: "Pig pluripotent stem cells would be useful in a number of ways, such as precisely engineering transgenic animals for organ transplantation therapies. The pig species is significantly similar to humans in its form and function, and the organ dimensions are largely similar to human organs. We could use embryonic stem cells or induced stem cells to modify the immune-related genes in the pig to make the pig organ compatible to the human immune system. Then we could use these pigs as organ donors to provide organs for patients that won't trigger an adverse reaction from the patient's own immune system.
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) `- ]* ~; u' Z" U# y"Pig pluripotent stem cell lines could also be used to create models for human genetic diseases. Many human diseases, such as diabetes, are caused by a disorder of gene expression. We could modify the pig gene in the stem cells and generate pigs carrying the same gene disorder so that they would have a similar syndrome to that seen in human patients. Then it would be possible to use the pig model to develop therapies to treat the disease.
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"To combat swine flu, for instance, we could make a precise, gene-modified pig to improve the animal's resistance to the disease. We would do this by first, finding a gene that has anti-swine flu activity, or inhibits the proliferation of the swine flu virus; second, we can introduce this gene to the pig via pluripotent stem cells – a process known as gene 'knock-in'. Alternatively, because the swine flu virus needs to bind with a receptor on the cell membrane of the pig to enter the cells and proliferate, we could knock out this receptor in the pig via gene targeting in the pig induced pluripotent stem cell. If the receptor is missing, the virus will not infect the pig."7 N! ?) f; u% `( ~5 L4 @, J
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In addition to medical applications for pigs and humans, Dr Xiao said his discovery could be used to improve animal farming, not only by making the pigs healthier, but also by modifying the growth-related genes to change and improve the way the pigs grow.
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4 J$ {/ {* L8 \However, Dr Xiao warned that it could take several years before some of the potential medical applications of his research could be used in the clinic.

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世界首次：中国科学家培育出猪的干细胞
( |0 r$ `( t9 ?该发现对于动物和人类健康具有深远影响
9 F# E' I8 J% ^7 M% |科学家已经把来自猪的细胞诱导转变成了多能干细胞——这种细胞就像胚胎干细胞一样，有能力发育成身体中的任何类型的细胞。这是全世界首次使用任何有蹄脚的动物（被称为有蹄类动物）的体细胞（不是精细胞或卵细胞的细胞）实现了这一成果。4 E1 t: Y) a4 V# H* R/ Z
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这项成就的意义深远。该研究可能为建立人类遗传病模型、培育供人类器官移植的转基因动物以及开发耐受猪流感等疾病的猪开创一条道路。
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这项研究是新创刊的《分子细胞生物学报》[1]今天（6月3日星期三）在网上发布的第一篇论文。- l& F) Y; M+ l* |1 d" F
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领导了该研究的肖磊博士说：“迄今为止，科学家在利用早期胚胎培育有蹄类动物的多能胚胎干细胞方面做了很多努力，但是没有成功。这是世界首次培育出驯化的有蹄类动物的多能干细胞。因此，这项研究是全新的、非常重要，而且对于人类和动物健康有许多应用。”
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肖博士领导着上海生物化学与细胞生物学研究所（中国上海）的干细胞实验室，他和同事通过使用转录因子重编程了来自一头猪的耳朵和骨髓的细胞，从而成功地培育出了诱导多能干细胞。通过一种病毒把这些重编程因子的混合物引入细胞中，这些细胞发生了变化并在实验室中发育成了胚胎样干细胞群。进一步的测试证明了它们确实有能力分化成组成了胚胎的三层（内胚层、中胚层和外胚层）的细胞类型——这是所有胚胎干细胞都具有的能力。从成功培育出诱导多能干细胞（iPS细胞）获得的信息意味着科学家继续培育来自猪或其他有蹄类动物胚胎的胚胎干细胞（ES细胞）将变得远远更加容易。
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6 ~, @; [! F% o' S. O肖博士说：“猪的多能干细胞有许多用途，诸如准确改造用于器官移植治疗的转基因动物。猪在形态和功能方面与人类相当类似，而且器官尺寸与人类器官在很大程度上类似。我们可以使用胚胎干细胞或诱导干细胞修改猪的与免疫有关的基因，从而让猪的器官与人类免疫系统兼容。然后我们可以使用这些猪作为器官供体为患者提供器官，而不会引发来自患者自身免疫系统的有害反应。”
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  T6 f7 x* V# y& u1 ?* f# m3 e“猪多能干细胞系还可以用于建立人类遗传病的模型。许多人类疾病，诸如糖尿病，是由基因表达障碍造成的。我们可以修改干细胞中的猪的基因，并培育出携带同样基因障碍的猪，从而让它们具有和人类患者类似的症状。然后就有可能使用这种猪模型开发治疗这种疾病的疗法。
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0 r, a$ r% E( I6 f, r“例如，为了应对猪流感，我们可以培育出一种准确的转基因猪，从而改善它对这种疾病的耐性。我们首先可以找到一种具有抗猪流感活动或者抑制猪流感病毒增殖的基因；然后，我们可以把这种基因通过多能干细胞引入到猪的体内——这个过程被称为基因‘敲入’，从而实现这一目标。另外，由于猪流感病毒需要与猪细胞膜上的一个受体结合才能进入细胞并进行增殖，我们可以通过对猪诱导多能干细胞进行基因打靶从而敲出这一受体。如果这个受体消失了，这种病毒也就不会感染猪了。”
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除了对于猪和人类的医学应用，肖博士说他的发现可以用于改善畜牧业，不仅仅通过让猪更健康，而且还通过修改与生长有关的基因以改变和改善猪生长的方式从而改善畜牧业。; ~0 g0 o' P/ i1 l
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然而，肖博士警告说，他的研究的一些潜在的医学应用可能还需要数年时间才能投入临床使用。
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0 `: s  @7 o: O+ p' I0 \; u( B他的研究的下一阶段是使用猪iPS细胞产生转基因猪，从而为患者提供器官，改善猪的品种或用于疾病耐受能力。这些经过修改的动物可以是“敲入”的猪，即使用iPS细胞或ES细胞把一段额外的遗传物质（诸如一段人类DNA）转移给猪的基因组，或者是“敲出”的猪，即用这种技术阻止一个特定基因发挥作用。, D1 P9 `2 ?5 C" b
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该杂志的主编李党生教授评论该研究时说；“这项研究非常令人激动，因为它代表了培育有蹄类物种的多能干细胞的首次严格证明，这将为培育出精确的转基因动物用于研究、治疗和农业用途提供有趣的机会。”
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4 n& ?5 I0 G( D" M[1] Generation of pig induced pluripotent stem cells with a drug-inducible system. Journal of Molecular Cell Biology. doi:10.1093/jmcb/jmp003