在星形和花朵形的模子里培養(yǎng)干細胞,？這多少聽起來有點不可思議。但更不可思議的還在后面：這兩種形狀的區(qū)別甚至能決定人體干細胞長成脂肪,，或是骨骼,。這是史上第一次，生物學(xué)家用幾何學(xué)來決定細胞的命運,。而這一成果,，將為培養(yǎng)干細胞成為各種可供病人移植的器官組織鋪平道路。
與此前科學(xué)家通常通過誘導(dǎo)干細胞來培養(yǎng)各種組織相比,，美國伊利諾伊州芝加哥大學(xué)Milan Mrksich教授及其團隊的這一成果可以稱為細胞的“物理變化”而非“化學(xué)變化”,。
美國伊利諾伊州芝加哥大學(xué)的Milan Mrksich教授與他的研究團隊制作了一些大約50微米寬的模子，這些模子類似于烘焙餅干的模具,，包括星形,、花朵形、方形、五邊形以及圓形,。在每一個模子里,，科學(xué)家放置了一個人體骨髓干細胞。作為干細胞的一種,，這些未成熟的細胞將長成血液,、骨骼以及脂肪組織。而這些模子均被浸沒在化學(xué)培養(yǎng)液里,，以便他們盡快生長,。
盡管接受的是同一種化學(xué)培養(yǎng)液，但放置在有角的模子（如星形,、矩形）里70%的干細胞最終成為了骨骼組織,。而相應(yīng)地，放置在弧形的模子（如圓形,、花朵形）里的干細胞大多成為了脂肪組織,。
Mrksich教授的團隊認為，在上述過程中,，起決定性作用的是模子邊的角度,。這些角度讓干細胞相互推阻，并促發(fā)細胞內(nèi)部的“壓力絲”,。最終,，這些有彈性的微型“壓力絲”撐起整個細胞，并形成各自特殊的內(nèi)部結(jié)構(gòu),。
“在星形的模子中,，尖銳的角度激活了纖長而強壯的‘壓力絲’成長，導(dǎo)致干細胞長得更‘堅硬’,，成為骨骼組織，”Mrksich教授說,，“同時,，花朵形模子的弧形邊緣則刺激細胞長出短小而柔軟的‘壓力絲’，從而使干細胞長成脂肪組織,。”
在其他學(xué)者看來,，幾何學(xué)的確能在某種程度上影響體內(nèi)細胞的成長命運。
“細胞在生長過程,、體內(nèi)游動過程中會改變其幾何形狀和機制,，”美國費城賓夕法尼亞大學(xué)的生物工程師ChristopherChen說到，“細胞很可能通過這些改變來誘發(fā)一些基因突變,，以便于自身更好地發(fā)展,。”（生物谷Bioon.com）
生物谷推薦原始出處：
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.
