The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment.
The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment.
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DOI：
10.1038/s41598-018-25700-5
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发表时间：
2018-05-16
影响因子：
4.6
通讯作者：
Boer J
中科院分区：
文献类型：
--
作者：
Leuning DG;Beijer NRM;du Fossé NA;Vermeulen S;Lievers E;van Kooten C;Rabelink TJ;Boer J
间充质基质细胞（MSC）分泌有助于器官稳态和组织特异性修复的因子。例如，肾血管周围间充质基质细胞（kPSC）可以通过分泌肝细胞生长因子（HGF）促进肾上皮修复，而骨髓MSC的分泌组引起免疫抑制。基质细胞在复杂的三维（3D）结缔组织结构中起作用，诱导构象适应。在这里，我们测试的假设，表面形貌和相关的细胞适应性决定基质细胞的功能，通过调整释放的细胞因子。为此，我们在TopoWell板中培养人骨髓和肾血管周围基质细胞，TopoWell板是一种定制的多孔板，含有76种独特的生物活性表面形貌。使用荧光成像，我们观察到细胞形状的深刻变化，伴随着MSC的分泌能力的主要定量变化。细胞因子分泌谱与细胞形态密切相关，并且具有基质细胞类型特异性。我们的数据表明，基质细胞的功能是由微环境的结构，并可以在一个工程设置操纵。我们的数据也对间充质基质细胞疗法的临床制造有影响，其中应考虑生物反应器扩增期间的表面形貌以保持治疗特性。
Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released. To this end, we cultured human bone marrow and kidney perivascular stromal cells in the TopoWell plate, a custom-fabricated multi-well plate containing 76 unique bioactive surface topographies. Using fluorescent imaging, we observed profound changes in cell shape, accompanied by major quantitative changes in the secretory capacity of the MSCs. The cytokine secretion profile was closely related to cell morphology and was stromal cell type specific. Our data demonstrate that stromal cell function is determined by microenvironment structure and can be manipulated in an engineered setting. Our data also have implications for the clinical manufacturing of mesenchymal stromal cell therapy, where surface topography during bioreactor expansion should be taken into account to preserve therapeutic properties.
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影响因子：
4.1
作者：
Beijer, Nick R. M.;Vasilevich, Aliaksei S.;de Boer, Jan
通讯作者：
de Boer, Jan
影响因子：
64.8
作者：
Mammoto, Akiko;Connor, Kip M.;Mammoto, Tadanori;Yung, Chong Wing;Huh, Dongeun;Aderman, Christopher M.;Mostoslavsky, Gustavo;Smith, Lois E. H.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
DOI：
10.1007/978-1-4939-3584-0_22
发表时间：
2016-01-01
期刊：
MESENCHYMAL STEM CELLS, 2 EDITION
影响因子：
--
作者：
Fernandes-Platzgummer, Ana;Carmelo, Joana G.;Cabral, Joaquim M. S.
通讯作者：
Cabral, Joaquim M. S.
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
3.7
作者：
Carrion, Bita;Kong, Yen P.;Kaigler, Darnell;Putnam, Andrew J.
通讯作者：
Putnam, Andrew J.