Articleβ Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas
Xiaobo Xu,1,5 Joke D\'Hoker,1,5 Geert Stang ,1,5 Stefan Bonn ,1,5 Nico De Leu,1,5 Xiangwei Xiao,1,5 Mark Van De Casteele,1,5 Georg Mellitzer,2,5 Zhidong Ling,1,5 Danny Pipeleers,1,5 Luc Bouwens,1,5 Raphael Scharfmann,3,4,5 Gerard Gradwohl,2,4,5 and Harry Heimberg1,4,5,
1 Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B1090 Brussels, Belgium 2 INSERM, U682, Development and Physiopathology of the Intestine and Pancreas, 67200 Strasbourg, France 3 INSERM, U845, Faculty of Medicine Necker, 75730 Paris, France 4 Beta Cell Biology Consortium, 2213 Garland Avenue, 9465 MRB IV, Nashville, TN 37323-0494, USA 5 JDRF Center for Beta Cell Therapy in Diabetes, Laarbeeklaan 103, B1090 Brussels, Belgium
Corresponding author
Harry Heimberg
harry.heimberg@vub.ac.be
Novel strategies in diabetes therapy would obviously benefit from the use of beta (β) cell stem/progenitor cells. However, whether or not adult β cell progenitors exist is one of the most controversial issues in today\'s diabetes research. Guided by the expression of Neurogenin 3 (Ngn3), the earliest islet cell-specific transcription factor in embryonic development, we show that β cell progenitors can be activated in injured adult mouse pancreas and are located in the ductal lining. Differentiation of the adult progenitors is Ngn3 dependent and gives rise to all islet cell types, including glucose responsive β cells that subsequently proliferate, both in situ and when cultured in embryonic pancreas explants. Multipotent progenitor cells thus exist in the pancreas of adult mice and can be activated cell autonomously to increase the functional β cell mass by differentiation and proliferation rather than by self-duplication of pre-existing β cells only.
发布于 2008-02-19 17:22:59 修改
损伤小鼠的胰腺促进产生了更多的胰岛素分泌细胞（下图，红色），左图为对照。
比利时研究人员近日研究发现，损伤大鼠的胰腺后，有一群细胞会自然地转变成胰岛素分泌细胞。科学家对这一发现极为感兴趣，因为它有可能揭示了胰腺细胞的变形能力，并对糖尿病治疗提供帮助。相关论文发表在1月25日的《细胞》（Cell）杂志上。
在糖尿病患者体内，胰腺内的胰岛素分泌细胞（又称β细胞）遭到破坏或反应迟缓，这使得机体无法正常调节血糖水平。糖尿病研究者的一个重要目标就是“哄骗”胰腺产生新的β细胞。科学家就一关键问题已争论多年，即胰腺内是否存在干细胞用来补充β细胞。2004年，哈佛大学生物学家Douglas Melton领导的小组尝试在小鼠胰腺内寻找这种干细胞，最后以失败告终。不过他们报告说，现有的β细胞能够增殖形成新的β细胞。
之前的研究还发现，钳住大鼠胰腺管使得消化酶无法进入小肠，能使胰腺内的β细胞量大约增长一倍。但是具体是胰腺内的哪种细胞产生了额外的β细胞并不清楚。
在最新的研究中，比利时维萨里大学（Vrije Universiteit）的Harry Heimberg和同事运用同样的实验手段损伤小鼠的胰腺，并运用遗传标记神经元素3（neurogenin 3）以寻找能转变成β细胞的胰腺细胞。结果研究人员在损伤后三天之内发现了带有这种基因的细胞，此外，阻止这一基因的表达会减少β细胞的增殖。当将这些带有神经元素3的细胞注入从小鼠胚胎取出的胰腺中后，它们发育成β细胞并产生了胰岛素，表明就是这些细胞在小鼠受伤的胰腺中形成了新的β细胞。
此次发现具有重要的意义，但是仍旧存在许多问题有待解决。比如，在不伤害器官的情况下，神经元素3细胞是否可被“哄骗”在正常人体胰腺中产生，以及是否可将它们转变成胰岛素分泌细胞。
Melton推测，这些细胞一开始应该是成熟的胰腺细胞，因为它们不具有干细胞的许多特征。他表示，此次研究表明了存在另外一种产生β细胞的机制，这也为寻找β细胞补充途径提供了一种新的可能的细胞来源。
Cell, Vol 132, 197-207, 25 January 2008
Articleβ Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas
Xiaobo Xu,1,5 Joke D\'Hoker,1,5 Geert Stang ,1,5 Stefan Bonn ,1,5 Nico De Leu,1,5 Xiangwei Xiao,1,5 Mark Van De Casteele,1,5 Georg Mellitzer,2,5 Zhidong Ling,1,5 Danny Pipeleers,1,5 Luc Bouwens,1,5 Raphael Scharfmann,3,4,5 Gerard Gradwohl,2,4,5 and Harry Heimberg1,4,5,
1 Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B1090 Brussels, Belgium
2 INSERM, U682, Development and Physiopathology of the Intestine and Pancreas, 67200 Strasbourg, France
3 INSERM, U845, Faculty of Medicine Necker, 75730 Paris, France
4 Beta Cell Biology Consortium, 2213 Garland Avenue, 9465 MRB IV, Nashville, TN 37323-0494, USA
5 JDRF Center for Beta Cell Therapy in Diabetes, Laarbeeklaan 103, B1090 Brussels, Belgium
Harry Heimberg
harry.heimberg@vub.ac.be
Novel strategies in diabetes therapy would obviously benefit from the use of beta (β) cell stem/progenitor cells. However, whether or not adult β cell progenitors exist is one of the most controversial issues in today\'s diabetes research. Guided by the expression of Neurogenin 3 (Ngn3), the earliest islet cell-specific transcription factor in embryonic development, we show that β cell progenitors can be activated in injured adult mouse pancreas and are located in the ductal lining. Differentiation of the adult progenitors is Ngn3 dependent and gives rise to all islet cell types, including glucose responsive β cells that subsequently proliferate, both in situ and when cultured in embryonic pancreas explants. Multipotent progenitor cells thus exist in the pancreas of adult mice and can be activated cell autonomously to increase the functional β cell mass by differentiation and proliferation rather than by self-duplication of pre-existing β cells only.
主题关键词标签(点击标签查看相关主题)：Cell 损伤 糖尿病 胰腺 有望 治疗