Tissue Eng Lecture_102413

In the of scharge light the crbc is oxygen carrying

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Unformatted text preview: tational model of angiogenic stimuli - • • - - Model workflow Diffusive exchange Oxygen diffusion 16 Computational model of angiogenic stimuli 17 Angiogenesis steps: Sprouting After angiogenesis cascade is initiated pro- and antiangiogenic signals guide sprouting blood vessel to its final destination Endothelial cells must clear a path through the vascular basement membrane and ECM Proteases • • Break down the structural barriers Cleave matrix-bound growth factors to alter concentration gradients 18 these cells are called phalanx cells or lateral base cells if next to the emerging sprout [6,7]. Pericytes are also associated with nascent vessels and affect endothelial cell responses to signals in poorly understood ways. Overall, pericyte coverage of a vessel is associated with quiescence, analogous to the understood, a recent study suggests that in some cases macrophages may act as chaperones to organize fusion events [17 ]. The recent recognition of sprouting angiogenesis as a multistaged process (Fig. 2) has been facilitated by in-vitro and in-vivo assays that are Angiogenesis steps: Sprouting 01:40 03:00 (a) 1:40 Stage 1 sprout initiation (b) 04:20 3:00 Stage 2 sprout guidance sFlt-1 & (c) 05:00 4:20 Stage 3 extension (d) 5:00 Stage 4 anastomosis sFlt-1 FIGURE 2. Stages of angiogenesis. Time lapse images of embryonic stem cell-derived vessels demonstrating the four ‘stages’ of endothelial sprouting angiogenesis described in the text: (a) sprout initiation, (b) sprout guidance (e.g., through a channel created by sFlt-1 binding VEGF around adjacent stalk cells), (c) sprout extension, and (d) sprout anastomosis. Endothelial cells (white) of mouse embryonic stem cell-derived vessels have been genetically modified to express eGFP and visualized using confocal microscopy. Time stamps ¼ time elapsed (h) since start of run. (Images courtesy of Dr John Chappell, Ph.D, University of North Carolina) [18 ,19 ,20 ,21 ]. 19 && && & && Angiogenesis steps: Sprouting • Endothelial cells explore their microenvironment using filopodia • Only selected cells along a capillary will be able to begin the sprouting process • • Sprouting vessel contains tip cells and stalk cells Computational models can simulate discrete cell behaviors that follow specific rules 20 Angiogenesis steps: Sprouting Important signaling pathways involved in sprouting • Tip cell selection • VEGF receptor 2 Delta-like ligand 4 (DLL4) and Notch1 Remove physical barriers and cleave VEGF - Proteases Matrix metalloproteinases (MMPs) 21 Angiogenesis steps: Sprouting VEGFR2 VEGFR1 VEGFR1 VEGFR2 Dll4 Notch Dll4 Dll4 Notch Vegfr1 Vegfr1 Vegfr2 Vegfr2 VEGFA VEGFR2 Vegfr1 Vegfr2 DsRed):WT VEGFA VEGFR1 Dll4 Dll4 Dll4 Notch VEGFR1 Dll4 Notch b vegfr1+/– : WT VEGFA WT : WT VEGFA VEGFR2 Dll4 Vegfr1 Vegfr2 WT (DsRed):Vegfr2+/egfp vegfr2+/– : WT a WT (DsRed):Vegfr1+/lacz 22 Computational model of sprouting Bentley, Gerhardt, and Bates. J Theor Biol. 2008 23 Computational model of guiding sprout formation Vempati, Popel, and Mac Gabhann. BMC Sys Biol. 2011 24 ned HSPG gra- the model that contains no sprout. EGF degradaany inte...
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This note was uploaded on 01/20/2014 for the course BME 410 taught by Professor Han during the Spring '08 term at USC.

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