Clot-entrapped blood cells in synergy with human mesenchymal stem cells create a pro-angiogenic healing response

被引:19
作者
Burkhardt, Melanie A. [1 ]
Gerber, Isabel [1 ]
Moshfegh, Cameron [1 ]
Lucas, Miriam S. [2 ]
Waser, Jasmin [3 ]
Emmert, Maximilian Y. [4 ]
Hoerstrup, Simon P. [4 ]
Schlottig, Falko [3 ,5 ]
Vogel, Viola [1 ]
机构
[1] Swiss Fed Inst Technol, Lab Appl Mechanobiol, Inst Translat Med, Dept Hlth Sci & Technol, Vladimir Prelog Weg 4, CH-8093 Zurich, Switzerland
[2] Swiss Fed Inst Technol, Sci Ctr Opt & Elect Microscopy ScopeM, CH-8093 Zurich, Switzerland
[3] Thommen Med AG, CH-2540 Grenchen, Switzerland
[4] Swiss Ctr Regenerat Med, CH-8091 Zurich, Switzerland
[5] Univ Appl Sci Northwestern Switzerland, Sch Life Sci, CH-4132 Muttenz, Switzerland
基金
瑞士国家科学基金会; 欧洲研究理事会;
关键词
EXTRACELLULAR-MATRIX SCAFFOLDS; WOUND REPAIR; BONE REPAIR; MACROPHAGE POLARIZATION; FIBRONECTIN; SURFACES; FIBRIN; REGENERATION; INFLAMMATION; MMP-9;
D O I
10.1039/c7bm00276a
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Blood clots stop bleeding and provide cell-instructive microenvironments. Still, in vitro models used to study implant performance typically neglect any possible interactions of recruited cells with surface-adhering blood clots. Here we study the interaction and synergies of bone marrow derived human mesenchymal stem cells (hMSCs) with surface-induced blood clots in an in vitro model by fluorescence microscopy, scanning and correlative light and electron microscopy, ELISA assays and zymography. The clinically used alkali-treated rough titanium (Ti) surfaces investigated here are known to enhance blood clotting compared to native Ti and to improve the healing response, but the underlying mechanisms remain elusive. Here we show that the presence of blood clots synergistically increased hMSC proliferation, extracellular matrix (ECM) remodelling and the release of matrix fragments and angiogenic VEGF, but did not increase the osteogenic differentiation of hMSCs. While many biomaterials are nowadays engineered to release pro-angiogenic factors, we show here that clot-entrapped blood cells on conventional materials in synergy with hMSCs are potent producers of pro-angiogenic factors. Our data might thus not only explain why alkali-treatment is beneficial for Ti implant integration, but they suggest that the physiological importance of blood clots to create pro-angiogenic environments on implants has been greatly underestimated. The importance of blood clots might have been missed because the pro-angiogenic functions get activated only upon stimulation by synergistic interactions with the invading cells.
引用
收藏
页码:2009 / 2023
页数:15
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