Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs
Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs
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DOI：
10.1016/j.biomaterials.2017.06.019
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发表时间：
2017-09-01
期刊：
影响因子：
14
通讯作者：
Geissler, Sven
中科院分区：
文献类型：
--
作者：
Qazi, Taimoor H.;Mooney, David J.;Geissler, Sven
间充质基质细胞（MSCs）分泌的旁分泌因子在组织再生过程中起着至关重要的作用。一般来说，这种旁分泌功能是否受到生物材料特性的影响，特别是那些用于细胞递送的生物材料，在很大程度上仍未被探索。在这里，我们研究了不同微环境下的三维培养——纳米多孔水凝胶（平均孔径约为5nm）和大孔支架（平均孔径约为120 μ m）——是否会影响间充质干细胞的分泌模式，从而导致对靶祖细胞（如成肌细胞）的不同旁分泌效应。我们报道，与水凝胶包裹的MSCs相比，支架种子MSCs显示出增强的分泌特征，并对各种成肌细胞功能（包括迁移和增殖）发挥有益的旁分泌作用。此外，我们发现支架种子细胞的旁分泌效应增强，部分归因于培养过程中n -钙粘蛋白介导的细胞间相互作用。在水凝胶中，细胞之间的这种物理相互作用被包封的基质所阻止。功能阻断n -钙粘蛋白会对MSCs对成肌细胞的分泌谱和旁分泌作用产生负面影响，与水凝胶包膜细胞相比，支架种子细胞的作用更强。总之，这些发现表明，MSCs的治疗效力可以通过促进细胞间相互作用的生物材料来增强。(C) 2017 Elsevier Ltd.版权所有。
Mesenchymal stromal cells (MSCs) secrete paracrine factors that play crucial roles during tissue regeneration. Whether this paracrine function is influenced by the properties of biomaterials in general, and those used for cell delivery in particular, largely remains unexplored. Here, we investigated if three-dimensional culture in distinct microenvironments - nanoporous hydrogels (mean pore size similar to 5 nm) and macroporous scaffolds (mean pore size similar to 120 mu m) - affects the secretion pattern of MSCs, and consequently leads to differential paracrine effects on target progenitor cells such as myoblasts. We report that compared to MSCs encapsulated in hydrogels, scaffold seeded MSCs show an enhanced secretion profile and exert beneficial paracrine effects on various myoblast functions including migration and proliferation. Additionally, we show that the heightened paracrine effects of scaffold seeded cells can in part be attributed to N-cadherin mediated cell-cell interactions during culture. In hydrogels, this physical interaction between cells is prevented by the encapsulating matrix. Functionally blocking N-cadherin negatively affected the secretion profile and paracrine effects of MSCs on myoblasts, with stronger effects observed for scaffold seeded compared to hydrogel encapsulated cells. Together, these findings demonstrate that the therapeutic potency of MSCs can be enhanced by biomaterials that promote cell cell interactions. (C) 2017 Elsevier Ltd. All rights reserved.