Project D: Curing the heart with fat stem cells

Department of Pathology & Medical Biology
Cardiovascular Regenerative Medicine Res.Grp. (CAVAREM)

Coordinators: M.C.Harmsen PhD, A.R. Bellu PhD
Type of research: Fundamental, Laboratory
Field: Regenerative Medicine, Stem Cell Biology

Background

Cardiovascular disease (CVD) accounts for 1/3rd of the mortalities in the industrialized world. Vascular dysfunction, in particular atherosclerosis, is a prelude to occlusion of coronary arteries and subsequent myocardial infarction. Current therapies comprise of rapid restoration of myocardial perfusion by PCI and anticoagulatory treatments. Yet, this does not prevent death of myocardial tissue and subsequent adverse remodeling. Rebuilding the heart is not possible yet, but novel therapies emerge. The past decade saw the advent of cardiac stem cell therapy: promising but not for every patient and never 100% cure (yet). Among the most promising of stem cells, that were administered to patients, were stem cells isolated from adipose tissue (fat), aka ADSC (adipose derived stem cells). These cells are easy to harvest, isolate and propagate by culture.

Their mode of action is far from understood and will be topic of the IRF. We have shown that ADSC secrete a host of growth factors, chemokines and other factors that affect the repair process of the heart after myocardial infarction. Among others, ADSC stimulate the formation of new blood vessels and might induce proliferation of heart muscle cells (cardiomyocytes or CM). We also know that ADSC can literally reinforce the heart through production of extracellular matrix (ECM) components. Yet, too much ECM would mean that the heart becomes too stiff i.e. dysfunctional. Finally, after a myocardial infarction, the first stage of repair is an inflammation. As it appears ADSC modulate this myocardial inflammation.

Our research goals are

1)      What is the influence of myocardial inflammation on ADSC?
2)      How is the secretion of ECM components by ADSC regulated?
3)      What is the mechanism by which ADSC induce proliferation of CM?

Approach for the project:

The CAVAREM research group heavily relies on laboratory research, which means that we perform animal experiments and that we have in vitro models for cardiovascular disease. In other words, we culture e.g. ADSC and CM (among others) and subject these to conditions that mimic myocardial infarction: low oxygen to represent the tissue ischemia and TNFalpha to mimic inflammation. Thus in the project, the students will have to (co)culture these cells. The effects are assessed by molecular and cellular techniques such as RT-PCR, western blotting, immunofluorescence staining to mention a few. Daily supervision will be by a PostDoc and a PhD student while the students will participate in the research group meetings too.