Project acronym ENGVASC
Project Engineering Vascularized Tissues
Researcher (PI) Shulamit Levenberg
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), LS7, ERC-2011-StG_20101109
Summary Vascularization, the process in which new blood vessels assemble, is fundamental to tissue vitality. Vessel network assembly within 3D tissues can be induced in-vitro by means of multicellular culturing of endothelial cells (EC), fibroblasts and cells specific to the tissue of interest. This approach supports formation of endothelial vessels and promotes EC and tissue-specific cell interactions. Such EC-dependent tube-like openings may also form the basis for improved media penetration to the inner regions of thick 3D constructs, allowing for enhanced construct survival and for effective engineering of large complex tissues in the lab. Moreover, our own breakthrough results describe the beneficial impact of in vitro prevascularization of engineered muscle tissue on its survival and vascularization upon implantation. These studies have also demonstrated that implanted vascular networks of in vitro engineered constructs, can anastomose with host vasculature and form functional blood vessels in vivo. However, the mechanisms underlying enhanced vascularization of endothelialized engineered constructs and implant-host vessel integration remain unclear. In this proposal, our research objectives are (1) to uncover the mechanisms governing in vitro vessel network formation in engineered 3D tissues and (2) to elucidate the process of graft-host vessel network integration and implant vessel-stimulated promotion of neovascularization in vivo. In addition, the impact of construct prevascularization on implant survival and function will be explored in animal disease models. While there are still many challenges ahead, should we succeed, our research could lay the foundation for significantly enhanced tissue construct vascularization procedures and for their application in regenerative medicine. In addition, it may provide alternative models for studying the vascularization processes in embryogenesis and disease.
Summary
Vascularization, the process in which new blood vessels assemble, is fundamental to tissue vitality. Vessel network assembly within 3D tissues can be induced in-vitro by means of multicellular culturing of endothelial cells (EC), fibroblasts and cells specific to the tissue of interest. This approach supports formation of endothelial vessels and promotes EC and tissue-specific cell interactions. Such EC-dependent tube-like openings may also form the basis for improved media penetration to the inner regions of thick 3D constructs, allowing for enhanced construct survival and for effective engineering of large complex tissues in the lab. Moreover, our own breakthrough results describe the beneficial impact of in vitro prevascularization of engineered muscle tissue on its survival and vascularization upon implantation. These studies have also demonstrated that implanted vascular networks of in vitro engineered constructs, can anastomose with host vasculature and form functional blood vessels in vivo. However, the mechanisms underlying enhanced vascularization of endothelialized engineered constructs and implant-host vessel integration remain unclear. In this proposal, our research objectives are (1) to uncover the mechanisms governing in vitro vessel network formation in engineered 3D tissues and (2) to elucidate the process of graft-host vessel network integration and implant vessel-stimulated promotion of neovascularization in vivo. In addition, the impact of construct prevascularization on implant survival and function will be explored in animal disease models. While there are still many challenges ahead, should we succeed, our research could lay the foundation for significantly enhanced tissue construct vascularization procedures and for their application in regenerative medicine. In addition, it may provide alternative models for studying the vascularization processes in embryogenesis and disease.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym IMAGO
Project Imaging regulatory pathways of angiogenesis
Researcher (PI) Michal Neeman
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS7, ERC-2008-AdG
Summary Homeostasis of multicellular tissues relies on accurate match of vascular supply and drain to the needs of the tissue. Multiple pathways are involved in detection, signalling and execution of the required steps involved in organization of blood and lymphatic vessels during embryonic development. Similar mechanisms are utilized for overcoming changes in tissue requirements also in adult tissues and in pathological processes. The goal of this work is to reveal the dynamic forces that shape the blood vessels during angiogenesis. In particular, we would like to explore the impact of interstitial convective flow in dynamic imprinting of growth factor signalling, thereby regulating vascular patterning. Angiogenesis is explored here as an example for a possible general role for interstitial convection of growth factors in determination of the fine spatial patterning of tissue morphogenesis in vertebrates. To achieve this goal, we will develop multi-modality tools for imaging the regulation of vascular patterning. In vivo imaging will then be utilized for mapping vascular patterning in pathological and physiological angiogenesis including tumours, wound repair, the preovulatory ovarian follicle and foetal implantation sites. Whole body optical, CT, ultrasound and MRI will be applied for non-invasive imaging of deep organs. Microscopic morphometric and molecular information will be derived from the macroscopic imaging data, using selective molecular imaging approaches and functional imaging tools with specific pharmacological models that will be developed to account for interstitial convective flow. Intravital two photon microscopy and fluorescence endoscopy will be used for high resolution evaluation of vascular patterning. The evaluation of novel mechanisms for spatial regulation of intercellular growth factor signalling, will allow us to define new potential targets for intervention, and to develop new tools for preclinical and clinical imaging of angiogenesis.
Summary
Homeostasis of multicellular tissues relies on accurate match of vascular supply and drain to the needs of the tissue. Multiple pathways are involved in detection, signalling and execution of the required steps involved in organization of blood and lymphatic vessels during embryonic development. Similar mechanisms are utilized for overcoming changes in tissue requirements also in adult tissues and in pathological processes. The goal of this work is to reveal the dynamic forces that shape the blood vessels during angiogenesis. In particular, we would like to explore the impact of interstitial convective flow in dynamic imprinting of growth factor signalling, thereby regulating vascular patterning. Angiogenesis is explored here as an example for a possible general role for interstitial convection of growth factors in determination of the fine spatial patterning of tissue morphogenesis in vertebrates. To achieve this goal, we will develop multi-modality tools for imaging the regulation of vascular patterning. In vivo imaging will then be utilized for mapping vascular patterning in pathological and physiological angiogenesis including tumours, wound repair, the preovulatory ovarian follicle and foetal implantation sites. Whole body optical, CT, ultrasound and MRI will be applied for non-invasive imaging of deep organs. Microscopic morphometric and molecular information will be derived from the macroscopic imaging data, using selective molecular imaging approaches and functional imaging tools with specific pharmacological models that will be developed to account for interstitial convective flow. Intravital two photon microscopy and fluorescence endoscopy will be used for high resolution evaluation of vascular patterning. The evaluation of novel mechanisms for spatial regulation of intercellular growth factor signalling, will allow us to define new potential targets for intervention, and to develop new tools for preclinical and clinical imaging of angiogenesis.
Max ERC Funding
2 278 344 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
