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Stem cell therapy of myocardial infarction

Directing adipose derived stem cells to the area at risk in the heart after myocardial infarction using targeted microbubbles. Development of a new molecular therapeutic technique.

Researchers: Tom Kokhuis, Klazina Kooiman, Nico de Jong

Problem definition
Cardiovascular diseases add a major contribution to morbidity and mortality in the western society. Heart attacks (myocardial infarction) are the main contributor to these cardiovascular diseases. A myocardial infarction is caused by an obstruction in one of the coronary arteries that normally supply the heart with blood resulting in an impaired function of the heart muscle. A promising tool to restore contractile function after myocardial infarction is stem cell therapy. Stem cells not only help with the formation of new vessels (angiogenesis), but might also replace lost cardiac muscle cells, since they have the capacity to differentiate into cardiac muscle cells. However, the major problem with stem cell therapy is the lack of persistence of sufficient numbers of stem cells at the site of injury. Less than 3% of the cells stay at the infarction site. It is not known what exactly happens to the other cells, because it is difficult to track these cells in vivo directly after injection.

Research
This project aims to overcome this problem by targeting the stem cells to the area at risk after myocardial infarction. The stem cells will be bound to tiny microbubbles (2-5 μm) and this stem cell-bubble complex will be targeted to specific molecules on the injured vessel wall.  

This will result in larger quantities of stem cells in the area at risk in the heart that can stimulate the formation of new vessels or can differentiate into cardiac muscle cells, and can thereby improve regeneration of the heart. Besides the possibility of carrying targeting ligands on the microbubbles, the presence of microbubbles has two main functionalities:

  • Microbubbles can be pushed towards the vessel wall using the radiation force of diagnostic ultrasound. This acoustic radiation force can also be applied to the stem cell-bubble complex,
    thereby facilitating the binding of the stem cell-bubble complex to the endothelium.
  • Imaging and tracking of individual stem cell-bubble complexes with diagnostic ultrasound, to investigate the fate of the stem cells.   

Embedding
This project is a cooperation between the VU University Medical Center and the Thoraxcenter Biomedical Engineering group of the Erasmus MC. It is implemented into the adipose stem cell research line of the Institute for Cardiovascular Research at the VU University Medical Center (ICaR-VU) and of the Skeletal Tissue Engineering Group Amsterdam (STEGA), the therapeutic research lines at the cardiology department of the Erasmus MC and the VU and the molecular imaging research line at the Erasmus MC.