Cocultivation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Reveals Antiapoptotic and Proangiogenic Effects

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Integrating bioartificial tissues into the host vasculature is a prerequisite for tissue engineering applications. Endothelial progenitor cells (EPCs) display a high angiogenic potential and a low donor-site morbidity, making them ideal for tissue engineering applications. In our study we used a murine EPC cell line (T17b) and rat mesenchymal stem cells (MSCs) for cocultivation experiments. MSCs were cocultured with increasing T17b EPC amounts. Furthermore, MSCs in monoculture were treated with conditioned medium (CM) from T17b EPCs and T17b EPCs were treated with CM from MSCs. Proliferation and apoptosis were quantified with a bromodeoxyuridine ELISA and a DNA fragmentation ELISA, respectively. Osteogenic differentiation was detected with an alkaline phosphatase assay and bone morphogenetic protein-2 ELISA. The production of proangiogenic molecules was measured with a matrix metalloproteinase-3 and vascular endothelial growth factor ELISA as well as nitric oxide assay. We could show that T17b EPCs stimulated MSC proliferation but not vice versa. On the other hand, MSCs promoted the cell survival of EPCs. The growth-inducing and antiapoptotic effects were dependent on heterotypic cell contacts and paracrine mediators. Moreover, proangiogenic growth factors were found in the coculture. Collectively, our results indicate that the coapplication of MSCs and T17b EPCs provides new perspectives for tissue engineering applications.

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