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dc.contributor.authorPaul, Jonathan D.
dc.contributor.authorCoulombe, Kareen K. L.
dc.contributor.authorToth, Peter T.
dc.contributor.authorZhang, Yanmin
dc.contributor.authorMarsboom, Glenn
dc.contributor.authorBindokas, Vytas P.
dc.contributor.authorSmith, David W.
dc.contributor.authorMurry, Charles E.
dc.contributor.authorRehman, Jalees
dc.date.accessioned2016-06-09T22:43:06Z
dc.date.available2016-06-09T22:43:06Z
dc.date.issued2013-11-01
dc.identifier.bibliographicCitationPaul, J. D., Coulombe, K. L., Toth, P. T., Zhang, Y., Marsboom, G., Bindokas, V. P., ... & Rehman, J. (2013). SLIT3–ROBO4 activation promotes vascular network formation in human engineered tissue and angiogenesis in vivo. Journal of molecular and cellular cardiology, 64, 124-131.en_US
dc.identifier.issn0022-2828
dc.identifier.urihttp://hdl.handle.net/10027/20716
dc.description.abstractSuccessful implantation and long-term survival of engineered tissue grafts hinges on adequate vascularization of the implant. Endothelial cells are essential for patterning vascular structures, but they require supportive mural cells such as pericytes/mesenchymal stem cells (MSCs) to generate stable, functional blood vessels. While there is evidence that the angiogenic effect of MSCs is mediated via the secretion of paracrine signals, the identity of these signals is unknown. By utilizing two functionally distinct human MSC clones, we found that so-called “pericytic” MSCs secrete the pro-angiogenic vascular guidance molecule SLIT3, which guides vascular development by directing ROBO4-positive endothelial cells to form networks in engineered tissue. In contrast, “non-pericytic” MSCs exhibit reduced activation of the SLIT3/ROBO4 pathway and do not support vascular networks. Using live cell imaging of organizing 3D vascular networks, we show that siRNA knockdown of SLIT3 in MSCs leads to disorganized clustering of ECs. Knockdown of its receptor ROBO4 in ECs abolishes the generation of functional human blood vessels in an in vivo xenogenic implant. These data suggest that the SLIT3/ROBO4 pathway is required for MSC-guided vascularization in engineered tissues. Heterogeneity of SLIT3 expression may underlie the variable clinical success of MSCs for tissue repair applications.en_US
dc.description.sponsorshipNIHen_US
dc.publisherJournal of Molecular and Cellular Cardiologyen_US
dc.subjectangiogenesisen_US
dc.subjectendothelial cellsen_US
dc.subjectMesenchymal Stem Cells (MSC)en_US
dc.subjectmesenchymal stem cellsen_US
dc.subjecttissue engineeringen_US
dc.titleSLIT3–ROBO4 activation promotes vascular network formation in human engineered tissue and angiogenesis in vivoen_US
dc.typeArticleen_US


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