Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture.
Cyclic strain anisotropy regulates valvular interstitial cell phenotype and tissue remodeling in three-dimensional culture.
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DOI：
10.1016/j.actbio.2012.01.006
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发表时间：
2012-05
影响因子：
9.7
通讯作者：
Butcher, Jonathan T.
中科院分区：
文献类型：
--
作者：
Gould, Russell A.;Chin, Karen;Santisakultarm, Thom P.;Dropkin, Amanda;Richards, Jennifer M.;Schaffer, Chris B.;Butcher, Jonathan T.
许多平面结缔组织表现出复杂的各向异性基质纤维排列，这对其生物力学功能至关重要。这种有组织的结构是由常驻成纤维细胞响应其环境中的机械力而产生和修改的。在发育、衰老和疾病过程中，施加的应变场的方向性发生显著变化，但应变方向对基质重塑的具体影响尚不清楚。目前平面组织的机械生物学研究仅限于等双轴或单轴拉伸，不能充分模拟许多体内环境。在这项研究中，我们实现了一种新的生物反应器系统，以证明在3D工程组织环境中，控制各向异性应变对成纤维细胞行为的独特影响，使用主动脉瓣间质成纤维细胞（维克）作为模型系统。接种细胞的3D胶原水凝胶经受在1Hz下保持恒定面积应变幅度长达96小时的循环各向异性应变曲线。双轴应变各向异性的增加导致细胞取向和胶原纤维排列沿着应变和细胞取向的主要方向被发现之前的纤维重组。细胞增殖和凋亡均随应变各向异性的增加而显著增加（P < 0.05）。虽然与未应变的对照组相比，周期性应变减少了波形蛋白和α-平滑肌肌动蛋白，但波形蛋白和α-平滑肌肌动蛋白的表达随着应变各向异性而增加，并且与方向相关（P < 0.05）。总的来说，这些结果表明，应变场各向异性是成纤维细胞表型，营业额和基质重组，这可能会通知正常和病理性重塑软组织的独立调节器。
Many planar connective tissues exhibit complex anisotropic matrix fiber arrangements that are critical to their biomechanical function. This organized structure is created and modified by resident fibroblasts in response to mechanical forces in their environment. The directionality of applied strain fields change dramatically during development, aging, and disease, but the specific effect of strain direction on matrix remodeling is less clear. Current mechanobiological inquiry of planar tissues is limited to equibiaxial or uniaxial stretch, which inadequately simulate many in vivo environments. In this study, we implement a novel bioreactor system to demonstrate the unique effect of controlled anisotropic strain on fibroblast behavior in 3D engineered tissue environments, using aortic valve interstitial fibroblast cells (VIC) as a model system. Cell seeded 3D collagen hydrogels were subjected to cyclic anisotropic strain profiles maintained at constant areal strain magnitude for up to 96 hours at 1Hz. Increasing anisotropy of biaxial strain resulted in increased cellular orientation and collagen fiber alignment along the principal directions of strain and cell orientation was found to precede fiber reorganization. Cellular proliferation and apoptosis were both significantly enhanced under increasing biaxial strain anisotropy (P < 0.05). While cyclic strain reduced both vimentin and alpha-smooth muscle actin compared to unstrained controls, vimentin and alpha-smooth muscle actin expression increased with strain anisotropy and correlated with direction (P < 0.05). Collectively, these results suggest that strain field anisotropy is an independent regulator of fibroblast cell phenotype, turnover, and matrix reorganization, which may inform normal and pathological remodeling in soft tissues.
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DOI：
10.1083/jcb.134.4.971
发表时间：
1996-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goldman RD;Khuon S;Chou YH;Opal P;Steinert PM
通讯作者：
Steinert PM
影响因子：
4.8
作者：
L'Heureux, N;Pâquet, S;Auger, FA
通讯作者：
Auger, FA
影响因子：
--
作者：
Garvin, J;Qi, B;Banes, AJ
通讯作者：
Banes, AJ
影响因子：
5.5
作者：
Hornberger, TA;Armstrong, DD;Esser, KA
通讯作者：
Esser, KA
影响因子：
3.7
作者：
Merryman, W. David;Lukoff, Howard D.;Sacks, Michael S.
通讯作者：
Sacks, Michael S.