骨架材料性质可决定细胞命运

sunsong7

无需添加特殊的诱导因子，骨架材料的性质、形态可决定细胞分化、组织形成、形态发生，研究人员生成由物理形态指导干细胞分化的方法与化学诱导法相比将更便捷、廉价和安全。( G, o. t2 E2 z7 s
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Shaping Up: Controlling a Stem Cell's Form Can Determine Its Fate
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$ }0 s" I& v- Y% k$ U) FBone-like cell growth on nanofibers: Confocal microscope images detail the growth of a human bone marrow stromal cell (actin filaments in the cell "skeleton" are stained orange) on a nanofiber scaffold (green). The structure of thin fibers encourages stem cells to develop into the elongated, branched form characteristic of mature bone cells. (Credit: Tison, Simon/NIST)
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2 u3 n+ _  ^2 @ScienceDaily (Sep. 13, 2011) — "Form follows function!" was the credo of early 20th century architects making design choices based on the intended use of the structure. Cell biologists may be turning that on its head. New research by a team working at the National Institute of Standards and Technology (NIST) reinforces the idea that stem cells can be induced to develop into specific types of cells solely by controlling their shape. The results may be important to the design of materials to induce the regeneration of lost or damaged tissues in the body.& Q1 `: N$ v0 Z* x8 V7 z
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Tissue engineering seeks to repair or re-grow damaged body tissues, often using some form of stem cells. Stem cells are basic repair units in the body that have the ability to develop into any of several different forms. The NIST experiments looked at primary human bone marrow stromal cells, adult stem cells that can be isolated from bone marrow and can "differentiate" into bone, fat or cartilage cells, depending.
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' Y1 b6 H2 T, v; S2 F; K4 N( _"Depending on what?" is one of the key questions in tissue engineering. How do you ensure that the stem cells turn into the type you need? Chemical cues have been known to work in cases where researchers have identified the proper additives -- a hormone in the case of bone cells. Other research has suggested that cell differentiation on flat surfaces can be controlled by patterning the surface to restrict the locations where growing cells can attach themselves.
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2 S, V/ z: t# ~* z# lThe experiments at NIST are believed to be the first head-to-head comparison of five popular tissue scaffold designs to examine the effect of architecture alone on bone marrow cells without adding any biochemical supplements other than cell growth medium. The scaffolds, made of a biocompatible polymer, are meant to provide a temporary implant that gives cells a firm structure on which to grow and ultimately rebuild tissue. The experiment included structures made by leaching and foaming processes (resulting in microscopic structures looking like clumps of insect-eaten lettuce), freeform fabrication (like microscopic rods stacked in a crisscross pattern) and electrospun nanofibers (a random nest of thin fibers). Bone marrow stromal cells were cultured on each, then analyzed to see which were most effective at creating deposits of calcium -- a telltale of bone cell activity. Microarray analysis also was used to determine patterns of gene expression for the cultured cells.# ]( p! _2 b7 f  C3 V, I
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The results show that the stem cells will differentiate quite efficiently on the nanofiber scaffolds -- even without any hormone additives -- but not so on the other architectures. The distinction, says NIST biologist Carl Simon, Jr., seems to be shape. Mature bone cells are characteristically long and stringy with several extended branches. Of the five different scaffolds, only the nanofiber one, in effect, forces the cells to a similar shape, long and branched, as they try to find anchor points. Being in the shape of a bone cell seems to induce the cells to activate the genes that ultimately produce bone tissue.. m" x4 j) w4 H* \5 Q- K4 t  {

, X: ~1 d' K; \8 |+ q"This suggests that a good strategy to design future scaffolds would be to take into account what shape you want to put the cells in," says Simon, adding, "That's kind of a tall order though, you'd have to understand a lot of stuff: how cell morphology influences cell behavior, and then how the three-dimensional structure can be used to control it." Despite the research still to be done on this method, the ability to physically direct cell differentiation by shape alone potentially would be simpler, cheaper and possibly safer than using biochemical supplements, he says.
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The work was supported in part by the National Institute of Dental and Craniofacial Research, National Institutes of Health.
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http://www.sciencedaily.com/releases/2011/09/110913172708.htm

wanghuantjmu

好方法，之前也看到一篇不同形状的生物容器，可以诱导细胞向不同的方向分化的报道，就是没有找到具体文献。

naturalkillerce

回复 sunsong7 的帖子8 }1 z) N" d( S, J& G

8 k" Z. n% v. Z- u5 u哈哈，我正在编译中，就是所谓“Form follows Function”，还是蛮有新意的，就是不知道实际应用到底有多大作用，不过很多事情，大多是从一点一滴做起的，希望未来有好的应用。

jijuling

Not a new but an interesting story.  

naturalkillerce

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回复 sunsong7 的帖子
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1 I  T# O  W5 S& i借用了你帖子的图片，由于编译后内容过多，就单独发贴了，不好意思啦。' x7 P5 j8 V. z4 Q9 x! d
另外，该研究成果发表在《生物材料》上，其摘要还明确指出，支架结构要比支架组成成分对hBMSC分化更有影响，hBMSCs对支架结构要比想象中敏感得多，人们可以通过调整支架结构使之最优化，以便更好地迫使hBMSCs转变形态从而指导它们分化为所需的细胞系。所以个人觉得“骨架材料性质可决定细胞命运”值得商榷，换成支架结构可以决定干细胞分化命运或许更能贴近原文。楼主你说呢？对了，我习惯将scaffold翻译为支架，这个是个人习惯而已，呵。
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) V, {1 `' m/ p4 M" ]- p* U+ l0 b附上摘要中相关句子：
/ v/ L- A" I8 H, d+ RHierarchical cluster analysis showed that treatments sorted by scaffold structure and not by polymer chemistry suggesting that scaffold structure was more influential than scaffold composition.
1 v. p& d. P& C9 f1 g9 b; zThese results indicate that cells are more sensitive to scaffold structure than previously appreciated and suggest that scaffold efficacy can be optimized by tailoring the scaffold structure to force cells into morphologies that direct them to differentiate down the desired lineage.

naturalkillerce

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回复 naturalkillerce 的帖子9 d$ G( s. ~* U. T
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中文编译参见下面的帖子，http://www.stemcell8.cn/thread-46288-1-1.html。另外，求原文啊，谁能下载原文和补充材料啊？慷慨一下 。

yepgangster

还是没有看懂到底怎么control the stem cell's form。细胞骨架又是怎么固定的。这样还是不能排除是信号分子等促进stem cell 分裂的啊，况且也只是bone cell

sunsong7

回复 yepgangster 的帖子
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“Form follows Function”/ L: y+ x3 A  D! z' o$ H% f( v! S4 U
“结构决定功能”是自然界的普遍法则，凸透镜和凹透镜的结构决定了其各自的光学性能；蛋白质氨基酸序列决定二级结构和高级构象形成疏水区、亲水区，决定了生物分子间“锁与钥匙”的构效关系；磷脂分子的脂肪酸链和磷酸集团决定生物膜双分子层排列，有机分子小分子、生物大分子、无机离子等选择性透过性；5 ]0 N" M- w, ^7 S
理论上各种生物过程均可还原到化学过程和最终的物理效应，纳米材料、石墨烯等支架材料的微观物理结构对干细胞生长分化的作用是方兴未艾的细胞力学研究内容；
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【扩展阅读】
. _8 I8 K7 ]4 C  E通过支架结构控制干细胞形态从而控制它的分化途径 http://www.stemcell8.cn/thread-46288-1-1.html
4 f3 t  S0 _( Q& P2 }% I# O中国人热火朝天干iPS细胞，美国人悄无声息搞aECM... http://www.stemcell8.cn/thread-40290-1-1.html
) D$ F- I' P4 ]" a细胞力学——新方法可预测干细胞分化过程 http://www.stemcell8.cn/thread-32635-1-1.html
. o3 l' U: v! q, [moving to a Graphene world（石墨烯专题）http://www.stemcell8.cn/thread-40002-1-1.html0 ^" d+ u7 v- K
物理环境（力学）对干细胞分化和肿瘤迁移影响的3篇文献 http://www.stemcell8.cn/thread-27403-1-1.html
' N6 l$ Z- [& `; G  d组织工程突破：给心脏打补丁令其自我修复 http://www.stemcell8.cn/thread-39519-1-1.html
. ?5 V5 z3 d4 l8 |1 {' D软骨损伤可做细胞移植打“补丁”http://www.stemcell8.cn/thread-26951-1-1.html) x$ S' ]: s% K" H
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naturalkillerce

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6 F9 [. ?9 c* y9 b+ i回复 yepgangster 的帖子
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  @! m# w6 S' N7 t支架结构(scaffold structure)对干细胞形态乃至其分化命运【此处是指人原代骨髓基质细胞(primary human bone marrow stromal cells)分化为骨细胞还是脂肪细胞，还是软骨细胞】的影响最终也是通过支架结构与干细胞的胞外结构和细胞膜上的分子相互作用，将支架结构的信息通过信号分子传导到细胞核，导致干细胞一些特异性基因激活【不同支架结构激活的基因有差别】，从而改变干细胞的微环境，也就改变了干细胞的形态，从而也就决定可干细胞的分化命运。支架是由生物可降解的大分子聚合物组成的，其固定比较容易吧。更详细信息可参见http://www.stemcell8.cn/thread-46288-1-1.html(通过支架结构控制干细胞形态从而控制它的分化途径)。