Abstract
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% O2 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.
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