内胚层祖细胞——安全、丰富的干细胞来源（附原文）
[i=s] 本帖最后由 细胞海洋 于 2012-4-8 12:04 编辑 [/i][align=center][size=5]New Stem Cell Line Provides Safe, Prolific Source for Disease Modeling and Transplant Studies[/size][/align]
ScienceDaily (Apr. 5, 2012) — Researchers have generated a new type of human stem cell that can develop into numerous types of specialized cells, including functioning pancreatic beta cells that produce insulin. Called endodermal progenitor (EP) cells, the new cells show two important advantages over embryonic stem cells and induced pluripotent stem cells: they do not form tumors when transplanted into animals, and they can form functional pancreatic beta cells in the laboratory.
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"Our cell line offers a powerful new tool for modeling how many human diseases develop," said study leader Paul J. Gadue, PhD, a stem cell biologist in the Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia. "Additionally, pancreatic beta cells generated from EP cells display better functional ability in the laboratory than beta cells derived from other stem cell populations."
In addition to producing beta cells, the researchers also directed EP cells to develop into liver cells and intestinal cells -- both of which normally develop from the endoderm tissue layer early in human development.
Gadue and colleagues are publishing their study April 6 in the journal Cell Stem Cell.
Reprogramming human stem cells into EP cells
The researchers manipulated two types of human stem cells -- embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) -- to become EP cells. Because both stem cell populations proliferate in great numbers and potentially generate all types of tissue, they offer enormous promise for scientists to precisely control cell development, both for the study of basic biology and for future cell-based treatments.
ESCs are derived from human embryos, typically unused embryos from fertility treatments that are donated for research purposes, while iPSCs are engineered from human somatic cells, such as skin cells or blood cells. Researchers have learned how to reprogram somatic cells to become pluripotent. Like ESCs, iPSCs are able to develop into many other types of human cells. However, when undifferentiated ESCs or iPSCs are transplanted in animal studies, they form teratomas, tumors containing many different cell types. Therefore, it has been critical that any cell type generated from ESCs or iPSCs and used for transplantation is stringently purified to exclude undifferentiated cells with tumor-forming potential.
In the current study, the researchers used signaling molecules called cytokines to steer ESCs and iPSCs into becoming EP cells, committed to developing into endoderm, one of the three tissue layers found in early human development. The EP cells have nearly unlimited potential for growth in the laboratory.
Benefits of EP cells
Both in cell cultures and when transplanted into animals, the study team showed that EP cells can differentiate into multiple cell types, representing those found in the liver, pancreas and intestine. Importantly, undifferentiated EP cells did not form teratomas in the team's transplantation studies.
In cell culture, the researchers differentiated the EP cells into beta cells -- insulin-expressing cells similar to those found in the pancreas. Those engineered beta cells passed an important test -- when stimulated by glucose, they were able to release insulin, a function that is impaired or absent in patients with diabetes. While the cells achieved only 20 percent of normal function, this result is an improvement over that seen in similar cells derived directly from ESCs or iPSCs, which typically respond very poorly or not at all to glucose.
Future research directions
Gadue stressed that these promising early results are only the first steps in researching EP cells. Further work may focus on taking cells from individual patients with genetic forms of diabetes or liver disease to derive EP cell lines. The EP cell lines can then be used to model the development and progression of the patient's disease and discover new therapies for that particular disease.
Finally, although applying this science to cell therapy is years away from practical clinical use, EP cells may offer a powerful starting point for developing tissue replacement treatments, such as supplying beta cells for diabetes patients or hepatocytes (liver cells) for patients with liver disease. "While more work is needed to characterize EP cells, they may offer a potential source of safe, abundant cells for future diabetes treatments," said Gadue.
Financial support for this study came from the National Institutes of Health. Co-authors with Gadue included Deborah L. French, PhD, Xin Cheng, PhD, and Mitchell J. Weiss, MD, PhD, all of The Children's Hospital of Philadelphia; Darrell Kotton, MD, of Boston University School of Medicine; and M. Cristina Nostro, PhD, of the McEwen Centre for Regenerative Medicine, Toronto, Canada.
Story Source:
The above story is reprinted from materials provided by Children's Hospital of Philadelphia.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
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Journal Reference:
1.Xin Cheng, Lei Ying, Lin Lu, Aline M. Galvão, Jason A. Mills, Henry C. Lin, Darrell N. Kotton, Steven S. Shen, M. Cristina Nostro, John Kim Choi, Mitchell J. Weiss, Deborah L. French, Paul Gadue. Self-Renewing Endodermal Progenitor Lines Generated from Human Pluripotent Stem Cells. Cell Stem Cell, 2012; 10 (4): 371 DOI: 10.1016/j.stem.2012.02.024
[url]http://www.sciencedaily.com/releases/2012/04/120405131423.htm[/url]
[color=Red]4楼原文 感谢zhusealin 提供[/color] 好像是内胚层祖细胞吧…… [quote][size=2][color=#999999]南宫燚岚 发表于 2012-4-7 14:48[/color] [url=forum.php?mod=redirect&goto=findpost&pid=613049&ptid=54501][img]static/image/common/back.gif[/img][/url][/size]
好像是内胚层祖细胞吧……[/quote]
没错，应该是“内胚层”，顺手敲成了“中胚层”，还请海洋更正一下，谢谢！ 看看 [b]回复 [url=forum.php?mod=redirect&goto=findpost&pid=613120&ptid=54501][color=Olive]sunsong7[/color] 的帖子[/url][/b]
已更正 看了报道有两点不明白，第一，内胚祖细胞来自于哪里？分布情况？第二，有没有什么特异性标志？让我感兴趣的是两点，一、有 pluripoten特性，但不致瘤，二、在future study中的个性化治疗。 你们觉得这篇文章够格发cell吗，我就的不是很创新。 [b]回复 [url=forum.php?mod=redirect&goto=findpost&pid=613920&ptid=54501][color=Olive]一一[/color] 的帖子[/url][/b]
应该是multipotent stem cells , 只能向有限的细胞方向分化，所以不滞留
但是我觉得用于治疗还要研究透怎么想胰腺肝和其他器官的分化。据我所知现在还是非常困难得到体外成熟beta cells [i=s] 本帖最后由 gres 于 2012-4-10 22:07 编辑 [/i]
为什么这个文献下完是个 html不是pdf，看不了呀，谁有能不能发一分直接给我的信箱，非常感谢。[email]sln_1981@msn.com[/email]
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