Julius Wolff Institute, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies & Berlin-Brandenburg School for Regenerative Therapies, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA.
Biomaterials. 2017 Sep;140:103-114. doi: 10.1016/j.biomaterials.2017.06.019. Epub 2017 Jun 18.
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 ∼5 nm) and macroporous scaffolds (mean pore size ∼120 μm) - 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.
间充质基质细胞（MSCs）分泌旁分泌因子，在组织再生过程中发挥着至关重要的作用。这种旁分泌功能是否受到生物材料特性的影响，特别是对细胞输送的生物材料特性的影响，在很大程度上仍未得到探索。在这里，我们研究了在不同的微环境中进行三维培养（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 120μm））是否会影响 MSCs 的分泌模式，进而导致对靶祖细胞（如成肌细胞）产生不同的旁分泌效应。我们报告称，与包封在水凝胶中的 MSCs 相比，支架接种的 MSCs 显示出增强的分泌谱，并对各种成肌细胞功能（包括迁移和增殖）产生有益的旁分泌效应。此外，我们还表明，支架接种细胞增强的旁分泌效应部分归因于培养过程中 N-钙黏蛋白介导的细胞-细胞相互作用。在水凝胶中，细胞之间的这种物理相互作用被包封基质所阻止。功能上阻断 N-钙黏蛋白会对 MSCs 对成肌细胞的分泌谱和旁分泌效应产生负面影响，与支架接种细胞相比，水凝胶包封细胞的影响更强。总之，这些发现表明，通过促进细胞-细胞相互作用的生物材料可以增强 MSCs 的治疗效力。
