细胞外基质可以指挥人体进行修复重建（附原文）

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在二十几年前的一个著名实验中，研究者把一只狗麻醉，并用一段小肠替换了它心脏周围的主动脉，结果发现小肠细胞变成了血管细胞，这其中起决定性作用的就是细胞外的基质。细胞外基质的主要成分是胶原蛋白和其他蛋白质。动物身上的细胞外基质最初被用来治疗肩肌腱损伤、疝气等损伤，后来，科学家意识到细胞外基质还可以指挥人体进行修复重建。甚至从别的动物身上取来的细胞外基质，发出的信号照样能让人体听从，构建出人体免疫系统可以接受的器官、组织。在这个过程中，细胞外基质发挥着两个基本作用，一是提供物理支撑，二是提供生理信号。

猪的肌肉组织的细胞外基质曾被植入人体帮助肌肉组织的重生。当动物的细胞外基质与人体的健康细胞接触的时候，人的身体将会分解动物基质，动物基质释放的信号分子会将干细胞召集过来，指导干细胞变成肌肉组织。另外，由于动物的细胞外基质被缝合到了人的肌肉上，会随肌肉一起感受到机械运动的重负，这会进一步促进干细胞分化成肌肉组织。

在帮助伤口愈合方面，动物的细胞外基质也可以发挥作用，甚至通过特殊的设计，可以使这种细胞外基质具备抗菌的能力。最终，移植到人的伤口处的动物细胞外基质将加速伤口愈合，并成为新生组织的一部分，而无需像传统材料一样进行拆线等工作。

转自：生物探索

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Biophysical regulation of epigenetic state and cell reprogramming文献检索：doi:10.1038/nmat3777" X% t: B" _$ |5 p% B* o
[p=22, null, left]Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells’ epigenetic state. Specifically, decreased histone deacetylase activity and upregulation of the expression of WD repeat domain 5 (WDR5)—a subunit of H3 methyltranferase—by microgrooved surfaces lead to increased histone H3 acetylation and methylation. We also show that microtopography promotes a mesenchymal-to-epithelial transition in adult fibroblasts. Nanofibrous scaffolds with aligned fibre orientation produce effects similar to those produced by microgrooves, suggesting that changes in cell morphology may be responsible for modulation of the epigenetic state. These findings have important implications in cell biology and in the optimization of biomaterials for cell-engineering applications.
  e9 b3 h7 ?' q' \$ v6 q  I$ b: {相关文章：用Matrix重建你的身体 http://www.guokr.com/article/437476/
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/ v0 u4 _5 m1 b" a. N* g; c% k2楼原文 感谢zb_ming 提供
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Extracellular-matrix tethering regulates stem-cell fate

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Britta Trappmann,1 Julien E. Gautrot,1, 2 John T. Connelly,2, 3 Daniel G. T. Strange,4 Yuan Li,5 Michelle L. Oyen,4 Martien A. Cohen Stuart,5 Heike Boehm,6, 7 Bojun Li,8 Viola Vogel,8 Joachim P. Spatz,6, 7 Fiona M. Watt2, 9 & Wilhelm T. S. Huck1, 10
7 Y% `2 k- k' V7 E. |Affiliations Contributions Corresponding authors Journal name: 4 j; g* U" g( t* R2 G* r
Nature Materials Volume: 11, Pages: 642–649 Year published: (2012) DOI: doi:10.1038/nmat3339
  h7 V6 r, P0 G4 MReceived 13 July 2011 Accepted 20 April 2012 Published online 27 May 2012 Corrected online 03 July 2012 Corrigendum (August, 2012)
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Supplementary information To investigate how substrate properties influence stem-cell fate, we cultured single human epidermal stem cells on polydimethylsiloxane (PDMS) and polyacrylamide (PAAm) hydrogel surfaces, 0.1 kPa–2.3 MPa in stiffness, with a covalently attached collagen coating. Cell spreading and differentiation were unaffected by polydimethylsiloxane stiffness. However, cells on polyacrylamide of low elastic modulus (0.5 kPa) could not form stable focal adhesions and differentiated as a result of decreased activation of the extracellular-signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling pathway. The differentiation of human mesenchymal stem cells was also unaffected by PDMS stiffness but regulated by the elastic modulus of PAAm. Dextran penetration measurements indicated that polyacrylamide substrates of low elastic modulus were more porous than stiff substrates, suggesting that the collagen anchoring points would be further apart. We then changed collagen crosslink concentration and used hydrogel–nanoparticle substrates to vary anchoring distance at constant substrate stiffness. Lower collagen anchoring density resulted in increased differentiation. We conclude that stem cells exert a mechanical force on collagen fibres and gauge the feedback to make cell-fate decisions.
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