貝塔細胞正常分泌胰島素是治療糖尿病的關鍵,。如果能將大量完全分化的成年細胞以受控方式轉變成能分泌胰島素的貝塔細胞的話,,糖尿病治療的前景將會改變,。雖然以前文獻中有幾個以這種方式生成貝塔細胞的例子,,但這個過程迄今為止是無法控制的,。
美國科研人員最新研究發(fā)現,患糖尿病的活小鼠的外分泌胰腺細胞可被重新編程(生物谷注:重編程即細胞的再程序化,使分化后的細胞重新分化的技術),,成為能夠產生胰島素的內分泌細胞,,與貝塔細胞相似,從一種分化狀態(tài)進入另一種分化狀態(tài),,中間并不需轉變成干細胞,。這種策略是基于早先關于胰腺發(fā)育中所涉及轉錄因子的研究成果:三種因子(Ngn3, Pdx1 和 Mafa)的組合是該過程中的關鍵成分。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 455, 627-632 (2 October 2008) | doi:10.1038/nature07314
In vivo reprogramming of adult pancreatic exocrine cells to β-cells
Qiao Zhou1, Juliana Brown2, Andrew Kanarek1, Jayaraj Rajagopal1 & Douglas A. Melton1
1 Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
2 Department of Pathology, Children's Hospital, Boston, Harvard Medical School, Harvard Stem Cell Institute, 300 Longwood Avenue, Boston, Massachusetts 02115-5724, USA
One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble -cells. The induced -cells are indistinguishable from endogenous islet -cells in size, shape and ultrastructure. They express genes essential for -cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.