Inadequate vascularization of in vitro-engineered tissue constructs after implantation is a major problem in most tissue-engineering applications. In this study we evaluated whether adipose tissue-derived stromal cells (ASCs), similar to bone marrow-derived stromal cells (BMSCs), can support the organization of endothelial cells into prevascular-like structures using an in vitro model. In addition, we investigated the mechanisms leading to the support of endothelial organization by these cells. We cultured human umbilical vein endothelial cells (HUVECs), ASCs, and BMSCs either alone or in combination in fibrin-embedded spheroids for 14 days. We found that BMSCs and ASCs formed cellular networks that expressed α smooth muscle actin and, in the case of ASCs, also CD34. Further, BMSCs and ASCs secreted hepatocyte growth factor and tissue inhibitor of metalloproteinase 1 and 2. In addition, ASC-conditioned medium induced HUVEC outgrowth, whereas BMSC-conditioned medium and hepatocyte growth factor-supplemented medium did not. Finally, both BMSCs and ASCs supported HUVEC organization into prevascular-like structures when cocultured. Our results suggest that both BMSCs and ASCs can support the formation of prevascular-like structures in vitro. Further, our findings indicate that cell-cell contacts and reciprocal signaling play an important role in the formation of these prevascular structures.

Adipose tissue, Bioactivity, Blood vessel prostheses, Bone, Bone marrow, CD34 antigen, Cell-cell contact, Cellular network, Cellular neural networks, Conditioned medium, Endothelial cells, Engineered tissues, Hepatocyte growth factor, Human bone marrow, Human umbilical vein endothelial cells, In-vitro, MMP1 protein, MMP2 protein, Metalloproteinases, Peptides, Self assembly, Smooth muscle actins, Stromal cells, Tissue engineering, Tissue inhibitor, Vascularization, adipose tissue, adult, article, blood vessel, bone marrow cell, cell communication, cell culture, coculture, cytology, endothelium cell, female, fibrin, gelatinase A, human, interstitial collagenase, male, metabolism, methodology, middle aged, multicellular spheroid, scatter factor, secretion, signal transduction, stroma cell, tissue engineering,
Tissue Engineering. Part A
This work was funded by the European Commission 7th Framework Programme; grant id fp7/221345 - Development of a model of in vitro endochondral ossification with neovascularisation (IVANG)
Erasmus MC: University Medical Center Rotterdam

Verseijden, F, Posthumus-van Sluijs, S.J, Pavljasevic, P, Hofer, S.O.P, van Osch, G.J.V.M, & Farrell, E. (2010). Adult human bone marrow-and adipose tissue-derived stromal cells support the formation of prevascular-like structures from endothelial cells in vitro. Tissue Engineering. Part A, 16(1), 101–114. doi:10.1089/ten.tea.2009.0106