Introduction: Rapid establishment of functional blood vessels is a prerequisite for successful tissue engineering.\r\nDuring vascular development, endothelial cells (ECs) and perivascular cells assemble into a complex regulating\r\nproliferation of ECs, vessel diameter and production of extracellular matrix proteins. The aim of this study was to\r\nevaluate the ability of mesenchymal stem cells (MSCs) to establish an endothelial-perivascular complex in\r\ntissue-engineered constructs comprising ECs and MSCs.\r\nMethods: Primary human ECs and MSCs were seeded onto poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLAco-\r\nDXO)) scaffolds and grown in dynamic culture before subcutaneous implantation in immunocompromised mice\r\nfor 1 and 3 weeks. Cellular activity, angiogenic stimulation and vascular assembly in cell/scaffold constructs seeded\r\nwith ECs or ECs/MSCs in a 5:1 ratio was monitored with real-time RT-PCR, ELISA and immunohistochemical\r\nmicroscopy analysis.\r\nResults: A quiescent phenotype of ECs was generated, by adding MSCs to the culture system. Decreased\r\nproliferation of ECs, in addition to up-regulation of selected markers for vascular maturation was demonstrated.\r\nBaseline expression of VEGFa was higher for MSCs compared with EC (P <0.001), with subsequent up-regulated\r\nVEGFa-expression for EC/MSC constructs before (P <0.05) and after implantation (P <0.01). Furthermore, an\r\ninflammatory response with CD11b + cells was generated from implantation of human cells. At the end of the\r\n3 week experimental period, a higher vascular density was shown for both cellular constructs compared with empty\r\ncontrol scaffolds (P <0.01), with the highest density of capillaries being generated in constructs comprising both ECs\r\nand MSCs.
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