|
| Status |
Public on Aug 18, 2013 |
| Title |
SLIT3-ROBO4 Activation Promotes Vascular Network Formation in Human Engineered Tissue and Angiogenesis in Vivo |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Successful 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.1-5 While there is evidence that the angiogenic effect of MSCs is mediated via the secretion of paracrine signals,6,7 the identity of these signals is unknown. Here, by utilizing two functionally distinct human MSC clones, we found that so-called “pericytic” MSCs secrete the pro-angiogenic neurovascular guidance molecule SLIT3,8 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 knockdown of SLIT3 in MSCs leads to disorganized clustering of ECs, and 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 regulates MSC-guided vascularization in engineered tissues. Heterogeneity of SLIT3 expression may underlie the variable clinical success of MSCs for tissue repair applications.
|
| |
|
| Overall design |
4 samples with 2 replicates each
|
| |
|
| Contributor(s) |
Kreutziger KL, Smith DW, Murry CE |
| Citation(s) |
24090675 |
| Submission date |
Jun 26, 2013 |
| Last update date |
Aug 16, 2018 |
| Contact name |
Kareen L Kreutziger |
| Organization name |
University of Washington
|
| Department |
Pathology
|
| Lab |
Murry
|
| Street address |
850 Republican Street
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA209636 |
Less...
More...