Tissue Eng Lecture_102413

End of vessel plasticity in tumors pericyte coverage

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: enesis steps: Stabilization and regression Important signaling pathways involved in sprouting • • • • • Platelet-derived growth factor (PDGF) Angiopoietins (Ang) Transforming growth factor-β1 (TGFB1) Activin receptor-like kinase 5 (ALK5) Notch signaling components 44 Angiogenesis steps: Stabilization and regression Development 138 (21) TIMP3 ANG1 models, aide and approac advance our Pericyte recruitment TIE2 TJ DLL4 notch NRARP WNT VEGFR2 Proliferation Stabilisation Key notch receptor TIMP3 Stalk cell DLL4 ligand ANG1 TIE2 Tight junction (TJ) Fig. 5. Vessel stabilisation. Stalk cells (purple) recruit pericytes (orange) D stabilise the vasculature, possibly through the production of Gruedens and Gerhardt.to evelopment. 2011 Note added A paper app recently disc extending sp (Jakobsson e ring assay, a nuclear track cells by low able to under their relativ effective elo velocity, orie under VEGF 45 Computational model of vessel stabilization : Snapshots of the developing capillary bed (top) and pericyte density (bottom) nsionless times (ø = t(days)/1.6). Only flowing vessels recruit pericytes and46 the McDougall, Chaplain, Stephanou, Anderson. Math Model Nat Phenom. 2008 te before pericyte density restricts all subsequent remodell C bed would be a worst case scenario for VDA type of omputational model of vessel stabilization treat illaries would need to be accessed by the injected drug. Mo circulated to the parent vessel, however, by way of the singl (a) (b) (c) ots of the pericyte density evolution at different dimens 47 Quantitative experiments to complement models Where do the data for models come from? • In vitro assays • Microfluidic techniques High-resolution imaging In vivo assays - Most conventional assays are not feasible for HTP Screening co- and multi-culture Zebrafish model 48 In vitro assays and imaging 49 Utilization of microfluidic devices 50 Utilization of microfluidic devices 51 Platforms to screen compounds 52 Timeline of the angiogenesis process Logsdon, Finley, Popel, and Mac Gabhann. J Cell Molec Med. 2013 (In press) 53 Lecture Outline Five steps of angiogenesis - Important signaling pathways Examples of systems biology studies Modeling approaches Case studies - Application to tissue engineering (Artel) VEGF pathway in tumor angiogenesis (Finley) Conclusions 54 Strategies for vascularizing engineered constructs When the aim is to enhance or restore diseased tissue, vascularization is essential Should the focus be on regenerative cells or functional vasculature? - Deliver growth factors to the tissues Deliver Stem cells and progenitor cells Biomaterial's with bioactive components Directly build construct with conduits and channels Artel, Mehdizadeh, Chiu, Brey, and Cinar. Tissue Eng. 2011 55 Case study: Application to tissue engineering Computational model aims to investigate: - What is relationship between vascularization and scaffold properties? - What are the optimal scaffold properties that promote vascularization? - What is the impact of pore structure on vessel invasion and network structure? Methods: agent-based model - Rules govern the behavior of sprouting vessel in the presence of fixed growth factor concentration profile 56 57...
View Full Document

This note was uploaded on 01/20/2014 for the course BME 410 taught by Professor Han during the Spring '08 term at USC.

Ask a homework question - tutors are online