Abstract
A monolayer of endothelial cells lines the entire circulatory system and create a barrier between the circulatory system and the tissues. To create and maintain an intact barrier, the individual cells have to connect tightly with their neighbors, which causes a highly correlated motion between the cells within the monolayer. The cells have to maintain this barrier while apoptotic cells are being replaced and even while new blood vessels are being created. Meanwhile they are constantly exposed to a shear stress from the ow of blood through the vessels. These extreme micro-environmental conditions are fascinating from a biophysical point of view.
The vasculature also plays a signi cant role in many pathologies. In diabetic blindness or ischemic diseases the ow of blood is insucient to sustain certain tissues or whole limbs. The creation of new blood vessels can relieve or treat such diseases. In other pathologies, such as the growth of cancerous tumors and metastasis, the creation of new blood vessels to these tumors worsen the condition and an inhibition of blood vessel creation will relieve the pathology.
The thesis is divided into three parts; Part 1 provides some general background knowledge of endothelial cells and cell motility; Part 2 describes the projects conducted with twodimensional motility; and Part 3 describes the projects conducted with three-dimensional motility.
The projects described in Part 2 all relate the endothelial cells' ability to maintain a barrier, both while creating new vessels and while the cells in the monolayer divide to maintaining the required cell density.
All tissues are vascularized to a certain extent. That means that the endothelial cells that constitute the vasculature are exposed to the full range of physical environment that native tissues exhibit. These are just some of the fascinating reasons to study endothelial cells. The main reason for the study of endothelial cells in this thesis is for the use of endothelial cells to create a vascular network for tissue engineering. The eld of tissue engineering has been able to grow small volumes of many kinds of tissues and holds great promises for treatments and regenerative therapies. It faces an important obstacle before such promises can be realized, the engineered tissues needs to be of a size large enough to function and to relieve the damaged bodily functions.
The current state of the art in tissue engineering is able to grow a variety of functional tissues, but the limiting factor remains the size that these tissues can be grown to. Relying solely on di usion for exchange of nutrients, oxygen and waste products, tissues can only be grown up to around 1 cm3 in size. The proposed solution is to engineer tissues around a vascular network and establishing a functional vascular sca old is currently the main focus in many tissue engineering labs.
The projects described in Part 2 aim at furthering the techniques that would enable us to overcome this obstacle and create vascular sca olds for tissue engineering.
Below is a summary of the thesis' general outline to give an overview of the thesis and provide the structure of how the di erent projects described in individual chapters relate to each other. Each chapter describes a separate project and will contain a small introduction that address the issues relevant to that particular chapter. In each chapter it is also denoted where the work presented was conducted, and if it was conducted in collaboration with anyone, who they were and what their contribution was.
The vasculature also plays a signi cant role in many pathologies. In diabetic blindness or ischemic diseases the ow of blood is insucient to sustain certain tissues or whole limbs. The creation of new blood vessels can relieve or treat such diseases. In other pathologies, such as the growth of cancerous tumors and metastasis, the creation of new blood vessels to these tumors worsen the condition and an inhibition of blood vessel creation will relieve the pathology.
The thesis is divided into three parts; Part 1 provides some general background knowledge of endothelial cells and cell motility; Part 2 describes the projects conducted with twodimensional motility; and Part 3 describes the projects conducted with three-dimensional motility.
The projects described in Part 2 all relate the endothelial cells' ability to maintain a barrier, both while creating new vessels and while the cells in the monolayer divide to maintaining the required cell density.
All tissues are vascularized to a certain extent. That means that the endothelial cells that constitute the vasculature are exposed to the full range of physical environment that native tissues exhibit. These are just some of the fascinating reasons to study endothelial cells. The main reason for the study of endothelial cells in this thesis is for the use of endothelial cells to create a vascular network for tissue engineering. The eld of tissue engineering has been able to grow small volumes of many kinds of tissues and holds great promises for treatments and regenerative therapies. It faces an important obstacle before such promises can be realized, the engineered tissues needs to be of a size large enough to function and to relieve the damaged bodily functions.
The current state of the art in tissue engineering is able to grow a variety of functional tissues, but the limiting factor remains the size that these tissues can be grown to. Relying solely on di usion for exchange of nutrients, oxygen and waste products, tissues can only be grown up to around 1 cm3 in size. The proposed solution is to engineer tissues around a vascular network and establishing a functional vascular sca old is currently the main focus in many tissue engineering labs.
The projects described in Part 2 aim at furthering the techniques that would enable us to overcome this obstacle and create vascular sca olds for tissue engineering.
Below is a summary of the thesis' general outline to give an overview of the thesis and provide the structure of how the di erent projects described in individual chapters relate to each other. Each chapter describes a separate project and will contain a small introduction that address the issues relevant to that particular chapter. In each chapter it is also denoted where the work presented was conducted, and if it was conducted in collaboration with anyone, who they were and what their contribution was.
| Original language | English |
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| Publisher | The Niels Bohr Institute, Faculty of Science, University of Copenhagen |
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| Publication status | Published - 2013 |