Institute of Materials Research, Division for Metallic Biomaterials, Helmholtz-Zentrum Geesthacht (HZG), Geesthacht 21502, Germany.
ACS Appl Bio Mater. 2021 Mar 15;4(3):2398-2407. doi: 10.1021/acsabm.0c01289. Epub 2021 Feb 26.
The interaction between mesenchymal stem cells (MSCs) and endothelial cells (ECs) holds a promising potential for the revascularization of osteoconductive grafts in orthopedics regeneration. Magnesium (Mg), as a well-studied degradable biomaterial already used in current medical practice, possesses osteoinductive properties. We investigated whether the physiochemical microenvironment, that is, the Mg and oxygen contents, further influences the MSC-modulating EC activities. Hypoxia, normoxia, and Mg degradation were represented by 5 and 20% O and gradient Mg degradation products, respectively. The migration of ECs in both EC mono- and MSC-EC coculture was increased in Mg with normoxia. Tube formation of ECs was reduced by Mg, especially in coculture and under normoxia. Compared to the monoculture, MSC-EC coculture exhibited significantly decreased content of proangiogenic cytokines but an increased amount of chemotactic factors. Semiquantitative real-time polymerase chain reaction revealed significant different profiles of the gene regulation under hypoxia, normoxia, different cell populations, and cell status. Investigation of heterotypic MSC-EC interactions in a mixed coculture system exhibited significantly increased proliferation under hypoxia. Transdifferentiation between MSCs and ECs was found to be reciprocally regulated by Mg degradation products in the two different oxygen conditions, probably because of the variable regulating effects of Mg on hypoxia-inducible factors. These results indicated the modulatory roles of oxygen tension and MSCs in combination with Mg or Mg-based degradable materials.
间充质干细胞 (MSCs) 与内皮细胞 (ECs) 的相互作用在骨科再生中具有促进骨诱导移植物再血管化的潜力。镁 (Mg) 作为一种已经在当前医学实践中使用的研究充分的可降解生物材料，具有成骨特性。我们研究了生理化学微环境（即 Mg 和氧含量）是否进一步影响 MSC 调节 EC 活性。缺氧、常氧和 Mg 降解分别由 5% 和 20% O 和梯度 Mg 降解产物来代表。在常氧条件下，Mg 促进了 EC 单层和 MSC-EC 共培养中 EC 的迁移。Mg 降低了 EC 的管形成，尤其是在共培养和常氧条件下。与单层培养相比，MSC-EC 共培养中促血管生成细胞因子的含量显著降低，但趋化因子的含量增加。半定量实时聚合酶链反应显示，在缺氧、常氧、不同细胞群和细胞状态下，基因调控的表达谱存在显著差异。在混合共培养系统中研究异质 MSC-EC 相互作用时，在缺氧条件下发现增殖显著增加。在两种不同氧条件下，Mg 降解产物可能通过对缺氧诱导因子的可变调节作用，发现 MSC 和 EC 之间的转分化被相互调节。这些结果表明了氧张力和 MSC 在与 Mg 或基于 Mg 的可降解材料结合时的调节作用。
