Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels.
Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels.
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DOI：
10.1038/nmat3586
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发表时间：
2013-05
期刊：
影响因子：
41.2
通讯作者：
Burdick JA
中科院分区：
文献类型：
--
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
虽然已知细胞-基质粘附相互作用调节干细胞分化，但对基本机制，特别是用于水凝胶内的直接三维（3D）包封的机制知之甚少。在这里，我们证明，在共价交联的透明质酸（HA）水凝胶中，人间充质干细胞（hMSCs）的分化是由降解介导的细胞牵引力的产生指导的，与细胞形态或基质力学无关。允许（限制）细胞介导降解的具有相等弹性模量的HA水凝胶内的hMSC表现出高（低）程度的细胞铺展和高（低）牵引，并有利于骨生成（脂肪生成）。此外，通过延迟的二次交联将允许性水凝胶转换为限制性状态，进一步减少了水凝胶降解，抑制了牵引，并在不改变扩展细胞形态的情况下引起从骨生成到脂肪生成的转换。此外，抑制张力介导的信号在许可的环境反映了延迟的二次交联的效果，而上调张力诱导成骨，即使在限制性环境。
Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional (3D) encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular-traction, independent of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that either permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). In addition, switching the permissive hydrogel to a restrictive state via delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Also, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.
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影响因子：
4.4
作者：
Bennett, Kristin P.;Bergeron, Charles;Plopper, George E.
通讯作者：
Plopper, George E.
影响因子：
14
作者：
Mann, BK;Gobin, AS;West, JL
通讯作者：
West, JL
DOI：
10.1073/pnas.0903269107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kilian, Kristopher A.;Bugarija, Branimir;Mrksich, Milan
通讯作者：
Mrksich, Milan
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM
影响因子：
16.6
作者：
Guvendiren, Murat;Burdick, Jason A.
通讯作者：
Burdick, Jason A.