Major Research Interest of the Lab

  • Cell-based therapy for myocardial infarction

Our main interest is to elaborate advanced therapeutic strategies for boosting the myocardial regeneration by enforcing adult stem cells (of endogenous and exogenous origin) to engraft into the infarcted myocardium and to contribute to the regeneration of the myocardial cells (cardiomyocytes, endothelial cells and smooth muscle cells).

Stem/progenitor cells are reported to importantly contribute to tissue regeneration in numerous ischemic diseases and are currently considered for therapeutic purposes. Our investigations make use of several experimental models of human ischemic diseases (animal models of myocardial infarction, hind limb ischemia, wire injury) as well as high resolution imaging technology and advanced cell-based assays. All these approaches are used to uncover the fundamental aspects of stem cell transplant, with direct implications for human health, as they may produce significant improvements in the life quality of patients with ischemic heart disease.

  • Fundamental mechanisms of cardiac function decline in natural ageing process

Aging is a progressive process of functional decline that develops at multiple levels and increases the risk for cardiovascular pathologies. Our lab is interested in the active role of cardiac fibroblasts (cFb) in the ventricular remodeling associated to the natural aging process, as well as in cell-specific signaling pathways upon interference with myocardial infarction. The population of cFb is composed of adventitial and interstitial fibroblasts, which are geometrically interspersed between cardiomyocytes and are of the appropriate molecular program to allow rapid responsiveness after injury.

Previous findings demonstrated that cFb is a unique cell type (as opposed to a generic body-wide cell) that retains its embryological cardiac identity and is engineered to make part of the cardiac microenvironment, with a critical role in the structural and mechanical maintenance of the cardiac tissue.

By analyzing the multi-OMICS signatures of various populations of cFb isolated from young and old individuals with and without myocardial infraction, we hope to identify the key drivers of cFb activation and their molecular alterations during the aging process. Besides, by deciphering the cross-talk between cFb and infiltrating immune cells within the aged heart, we attempt to identify molecular targets that short-circuit the feed-forward signaling pathways leading to adverse ventricular remodeling on old individuals with myocardial infarction in the hopes of better preserving tissue integrity long-term.

  • Oxygen sensing mechanisms in mesenchymal stromal cell biology

Welcome to the Laboratory of Stem Cell Biology

Expertise

Cell culture expertise:

- derivation of cell lines: mesenchymal stromal cells (human and mouse), endothelial progenitor cells (human and mouse), rat neonatal cardiomyocytes, mouse embryonic stem cells (ESC), etc;

- in vitro ischemia models;

- cell-cell interactions;

- xCELLigence analysis;

- 3D culture systems (aggregates, co-cultures, hanging-drops; in vitro transplant systems)

- biocompatibility assays.

 

Experimental modelling:

- mouse model of myocardial infarction (by permanent ligation of the left coronary artery);

- mouse model of cardiac ischemia-reperfusion, which is able to generate infarct with variable size, according to the length of ischemia period;

- mouse model of hind limb ischemia;

 

Imaging analysis:

- Confocal microscopy (Leica TCS-SP5)

- Ecocardiography (VEVO 2100, Visualsonics)

- In vivo imaging (IVIS Spectrum, Perkin Elmer)

- Fluorescence-activated cell sorting (MoFlo Astrios, Beckman Coulter)

 

Molecular biology assays: cloning, transfection, qRT-PCR, PCR.