Cell-controlled dynamic surfaces for skeletal stem cell growth and differentiation.
Cell-controlled dynamic surfaces for skeletal stem cell growth and differentiation.
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DOI：
10.1038/s41598-022-12057-z
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发表时间：
2022-05-17
影响因子：
4.6
通讯作者：
Dalby, Matthew J.
中科院分区：
文献类型：
--
作者：
Anderson, Hilary J.;Sahoo, Jugal Kishore;Wells, Julia;van Nuffel, Sebastiaan;Dhowre, Hala S.;Oreffo, Richard O. C.;Zelzer, Mischa;Ulijn, Rein V.;Dalby, Matthew J.
骨骼干细胞（ssc，或间充质基质细胞，通常称为骨髓间充质干细胞）是一种动态的祖细胞群，可以根据再生需求和生态位环境的提示进入静止状态、自我更新或分化。然而，在体外培养中，它们通常生长在坚硬的聚苯乙烯表面上，这导致SSC表型的快速丧失。虽然可以控制SSC生长和分化的材料正在开发中，但迄今为止，很少有反映干细胞塑性性质的动态界面的例子被开发出来。由于相互竞争的需求，实现这样的界面是具有挑战性的：生长的SSCs需要较低的细胞粘附和细胞内张力，而分化成骨形成的成骨细胞则需要增加粘附和细胞内张力。我们之前报道了一个动态界面，其中细胞粘附三肽精氨酸-甘氨酸-天冬氨酸（RGD）被用户添加的弹性蛋白酶激活后呈现给细胞，该弹性蛋白酶裂解了一个巨大的阻断基团，将RGD隐藏在细胞之外。这允许生长阶段，而阻断组在适当的位置，细胞只能形成较小的粘连，随后是一个成骨细胞分化阶段，在加入弹性蛋白酶后，引发RGD暴露和随后的细胞粘连和收缩。在这里，我们的目标是开发一个自主系统，在该系统中，根据细胞的需要，通过使用基质金属蛋白酶（MMP）可切割肽序列来去除阻断基团，并假设SSCs在细胞到达合流时会产生更高水平的MMP。目前的研究表明，ssc产生活性的MMP-2，可以在表面上切割官能团。我们还证明，ssc可以在未断裂的表面生长，并随着时间的推移，在mmp反应表面产生成骨标记蛋白。这些研究证明了细胞控制表面可以调节粘附和表型的概念，对干细胞表型调节具有重要意义。
Skeletal stem cells (SSCs, or mesenchymal stromal cells typically referred to as mesenchymal stem cells from the bone marrow) are a dynamic progenitor population that can enter quiescence, self-renew or differentiate depending on regenerative demand and cues from their niche environment. However, ex vivo, in culture, they are grown typically on hard polystyrene surfaces, and this leads to rapid loss of the SSC phenotype. While materials are being developed that can control SSC growth and differentiation, very few examples of dynamic interfaces that reflect the plastic nature of the stem cells have, to date, been developed. Achieving such interfaces is challenging because of competing needs: growing SSCs require lower cell adhesion and intracellular tension while differentiation to, for example, bone-forming osteoblasts requires increased adhesion and intracellular tension. We previously reported a dynamic interface where the cell adhesion tripeptide arginine-glycine-aspartic acid (RGD) was presented to the cells upon activation by user-added elastase that cleaved a bulky blocking group hiding RGD from the cells. This allowed for a growth phase while the blocking group was in place and the cells could only form smaller adhesions, followed by an osteoblast differentiation phase that was induced after elastase was added which triggered exposure of RGD and subsequent cell adhesion and contraction. Here, we aimed to develop an autonomous system where the surface is activated according to the need of the cell by using matrix metalloprotease (MMP) cleavable peptide sequences to remove the blocking group with the hypothesis that the SSCs would produce higher levels of MMP as the cells reached confluence. The current studies demonstrate that SSCs produce active MMP-2 that can cleave functional groups on a surface. We also demonstrate that SSCs can grow on the uncleaved surface and, with time, produce osteogenic marker proteins on the MMP-responsive surface. These studies demonstrate the concept for cell-controlled surfaces that can modulate adhesion and phenotype with significant implications for stem cell phenotype modulation.
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影响因子：
14
作者：
Ho-Shui-Ling A;Bolander J;Rustom LE;Johnson AW;Luyten FP;Picart C
通讯作者：
Picart C
DOI：
10.1042/bcj20190382
发表时间：
2020-09-18
期刊：
The Biochemical journal
影响因子：
--
作者：
Childs PG;Reid S;Salmeron-Sanchez M;Dalby MJ
通讯作者：
Dalby MJ
影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
5.2
作者：
Mirmalek-Sani, Sayed-Hadi;Tare, Rahul S.;Oreffo, Richard O. C.
通讯作者：
Oreffo, Richard O. C.
影响因子：
41.2
作者：
Khetan S;Guvendiren M;Legant WR;Cohen DM;Chen CS;Burdick JA
通讯作者：
Burdick JA