6月7日,，德國(guó)教育與科研部成立的肝功能系統(tǒng)研究小組發(fā)表公報(bào)說(shuō)，他們用電腦模擬了肝臟的再生過(guò)程,，且其結(jié)果在實(shí)驗(yàn)中得到證實(shí),。這一方法將有助于改善肝硬化等肝臟疾病的治療。
肝臟是新陳代謝中最重要的器官之一,，負(fù)責(zé)清除血液毒素等重要任務(wù),。肝臟還有令人驚訝的再生能力，即使受損超過(guò)50％還能幾乎完全再生,。學(xué)界至今對(duì)肝臟的再生能力所知甚少,。
由德國(guó)和法國(guó)研究人員組成的研究小組利用電腦和系統(tǒng)生物學(xué)方法進(jìn)行研究，引入各種參數(shù)并建立數(shù)學(xué)模型,，成功模擬了化學(xué)中毒實(shí)驗(yàn)鼠肝臟的再生過(guò)程,，并在后來(lái)的實(shí)體實(shí)驗(yàn)中證實(shí)了電腦預(yù)測(cè)結(jié)果的準(zhǔn)確性。
研究人員說(shuō),，能夠模擬如此復(fù)雜的機(jī)制和準(zhǔn)確預(yù)測(cè)器官改變的電腦模型非常罕見(jiàn),。這種方法有非常廣泛的應(yīng)用前景，例如可以用于模仿癌細(xì)胞在人體中的擴(kuò)散等,。(生物谷Bioon.com)
MCP：2型糖尿病發(fā)病過(guò)程中肝臟線粒體蛋白質(zhì)組及其修飾的動(dòng)態(tài)變化
Science ：一種肝臟蛋白質(zhì)可幫助分泌胰島素
Hepatology：發(fā)現(xiàn)Cdc42在肝臟再生過(guò)程中調(diào)控的新機(jī)制
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.0909374107
Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration
Stefan Hoehmea,1, Marc Brulportb,1, Alexander Bauerb, Essam Bedawyb, Wiebke Schormannb, Matthias Hermesb, Verena Puppeb, Rolf Gebhardtc, Sebastian Zellmerc, Michael Schwarzd, Ernesto Bockampe, Tobias Timmelf, Jan G. Hengstlerb,2, and Dirk Drasdoa,g,2
aInterdisciplinary Centre for Bioinformatics (IZBI), University of Leipzig, H?rtelstrasse 16-18, D-04107 Leipzig, Germany;
bLeibniz Research Centre for Working Environment and Human Factors (IfADo); University of Dortmund, Ardeystrasse 67, D-44139 Dortmund, Germany;
gInstitut National de Recherche en Informatique et en Automatique (INRIA), Unit Rocquencourt B.P. 105, 78153, Le Chesnay Cedex, France;
dInstitute of Experimental and Clinical Pharmacology and Toxicology, Department of Toxicology, University of Tübingen, Wilhelmstrasse 56, 72074 Tübingen, Germany;
cInstitute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany;
eClinical School of the Johannes Gutenberg–University Mainz Institute for Toxicology, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany; and
fBiofluidmechanics Laboratory, Charite–Universit?tsmedizin Berlin, Berlin, Germany
Only little is known about how cells coordinately behave to establish functional tissue structure and restore microarchitecture during regeneration. Research in this field is hampered by a lack of techniques that allow quantification of tissue architecture and its development. To bridge this gap, we have established a procedure based on confocal laser scans, image processing, and three-dimensional tissue reconstruction, as well as quantitative mathematical modeling. As a proof of principle, we reconstructed and modeled liver regeneration in mice after damage by CCl4, a prototypical inducer of pericentral liver damage. We have chosen the regenerating liver as an example because of the tight link between liver architecture and function: the complex microarchitecture formed by hepatocytes and microvessels, i.e. sinusoids, ensures optimal exchange of metabolites between blood and hepatocytes. Our model captures all hepatocytes and sinusoids of a liver lobule during a 16 days regeneration process. The model unambiguously predicted a so-far unrecognized mechanism as essential for liver regeneration, whereby daughter hepatocytes align along the orientation of the closest sinusoid, a process which we named “hepatocyte-sinusoid alignment” (HSA). The simulated tissue architecture was only in agreement with the experimentally obtained data when HSA was included into the model and, moreover, no other likely mechanism could replace it. In order to experimentally validate the model of prediction of HSA, we analyzed the three-dimensional orientation of daughter hepatocytes in relation to the sinusoids. The results of this analysis clearly confirmed the model prediction. We believe our procedure is widely applicable in the systems biology of tissues.
