在星形和花朵形的模子里培养干细胞？这多少听起来有点不可思议。但更不可思议的还在后面：这两种形状的区别甚至能决定人体干细胞长成脂肪，或是骨骼。这是史上第一次，生物学家用几何学来决定细胞的命运。而这一成果，将为培养干细胞成为各种可供病人移植的器官组织铺平道路。
与此前科学家通常通过诱导干细胞来培养各种组织相比，美国伊利诺伊州芝加哥大学Milan Mrksich教授及其团队的这一成果可以称为细胞的“物理变化”而非“化学变化”。
美国伊利诺伊州芝加哥大学的Milan Mrksich教授与他的研究团队制作了一些大约50微米宽的模子，这些模子类似于烘焙饼干的模具，包括星形、花朵形、方形、五边形以及圆形。在每一个模子里，科学家放置了一个人体骨髓干细胞。作为干细胞的一种，这些未成熟的细胞将长成血液、骨骼以及脂肪组织。而这些模子均被浸没在化学培养液里，以便他们尽快生长。
尽管接受的是同一种化学培养液，但放置在有角的模子（如星形、矩形）里70%的干细胞最终成为了骨骼组织。而相应地，放置在弧形的模子（如圆形、花朵形）里的干细胞大多成为了脂肪组织。
Mrksich教授的团队认为，在上述过程中，起决定性作用的是模子边的角度。这些角度让干细胞相互推阻，并促发细胞内部的“压力丝”。最终，这些有弹性的微型“压力丝”撑起整个细胞，并形成各自特殊的内部结构。
“在星形的模子中，尖锐的角度激活了纤长而强壮的‘压力丝’成长，导致干细胞长得更‘坚硬’，成为骨骼组织，”Mrksich教授说，“同时，花朵形模子的弧形边缘则刺激细胞长出短小而柔软的‘压力丝’，从而使干细胞长成脂肪组织。”
在其他学者看来，几何学的确能在某种程度上影响体内细胞的成长命运。
“细胞在生长过程、体内游动过程中会改变其几何形状和机制，”美国费城宾夕法尼亚大学的生物工程师ChristopherChen说到，“细胞很可能通过这些改变来诱发一些基因突变，以便于自身更好地发展。”（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS March 1, 2010, doi: 10.1073/pnas.0903269107
Geometric cues for directing the differentiation of mesenchymal stem cells
Kristopher A. Kiliana,c, Branimir Bugarijab,c, Bruce T. Lahnb,c, and Milan Mrksicha,c,1
aDepartment of Chemistry,
bDepartment of Human Genetics, and
cHoward Hughes Medical Institute, The University of Chicago, Chicago, IL 60637
Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature—and with each occupying the same area—display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
