Modeling an angiogenesis treatment after a myocardial infarction
Linda Crapts
Supervisor: Fred Vermolen

Site of the project: TU Delft

start of the project: December 2011

In April 2012 the Interim Thesis and a presentation has been given.

The Master project has been finished in September 2012 by the completion of the Masters Thesis and a final presentation has been given.

For working address etc. we refer to our alumnipage.

Summary of the master project:
A combination of bad lifestyle and genetic deficiencies may result into a myocardial infarction (or commonly called 'heart attack'). This infarction represents the decease of myocardial tissue (death of heart cells in the heart muscle) as a result of insufficient supply of oxygen and nutrients, which results from poor blood supply through the arteries. This defect is commonly caused by a large built- up of fatty acids and cholesterol in the arteries. The dead cells in the affected heart region, cause an excessive secretion of collagen, which results into scar tissue with stiff mechanical properties. These mechanical properties will result into a higher resistence of the pump function to be carried by the heart muscle. This higher resistence, which frustrates the pump function, will result into growth of the present myocites cells as a natural reaction of all muscle cells to hard labor. As a result, the muscle cells will decease more rapidly than in circumstances without a heart attack, which eventually will result into heart failure, and hence in death of the patient.

In order to prevent formation of scar tissue, a new treatment is currently being investigated, in which stem cells are injected onto affected regions of the heart. These stem cells secrete, among many others, the growth factor TG-beta, which enhances angiogenesis in the sense that
  1. endothelial cells are provoked to move towards the 'wound' (chemotaxis);
  2. endothelial cells are provoked to divide, by which new arteries are formed and extended (proliferation).
In this project, we construct a continuum-based mathematical model, which consists of a set of non-linearly coupled partial differential equations, with a predominant hyperbolic structure due to a dominance of chemotaxis over random walk. This causes numerical challenges in the sense that TVD-schemes will be important. Since a three-dimensional approach with an adapting heart geometry will be the long-term goal, we will scrutinize the use of discontinuous Galerkin methods with triangular (tetrahedral) elements. The important questions, we want to answer, are the following:
  1. How many stemcells should be injected?
  2. How should they be injected with respect to adherence on the heart tissue?
  3. How does this situation change if a patient suffers from diabetes?
The last question is motivated by the detrimental correlation between the probability of the event 'heart attack' and the occurrence of 'diabetes'. Diabetes will result into stiffer arteries and a reduced supply of blood.

Heart with dead heart muscle

Application of stem cells

Contact information: Kees Vuik

Back to the home page or the Master students page of Kees Vuik