Aplicación terapéutica de la bioingeniería mediante la combinación de células madre y matrices extracelulares en un modelo de infarto de miocardio en rata

Résumé

THERAPEUTIC APPLICATION OF BIOENGINEERING BY COMBINING STEM CELLS AND EXTRACELLULAR MATRICES IN A RAT MODEL OF MYOCARDIAL INFARCTION Heart failure is the leading cause of death worldwide and the stem cell application has been deeply studied as a potential alternative therapy. One of the main limitations that this therapy has presented has been the low level of engraftment and survival of the cells after transplantation and therefore diminished efficacy. Thus, the use of biodegradable extracellular matrices may facilitate both the in vivo cell administration and its retention in the damaged tissue, potentiating its positive effect on the infarcted heart. The aim of this project was to study the therapeutic benefit of a stem cell population derived from the adipose tissue (ADSC) transplanted on biomatrices in a model of chronic myocardial infarction in rats. With this purpose, a rat ADSC cell population was isolated and characterized, and the biocompatibility of a collagen type-I membrane with the cells and the heart tissue was confirmed. Next, the cardiovascular regenerative potential of the ADSC patch was analyzed in a model of chronic myocardial infarction in rats. As a result of this, the treatment with the ADSC-cellularized membrane induced a long-term improvement in the cardiac function with a significant increase in the left ventricular ejection fraction (ADSC-membrane ΔLVEF: 15.6 ± 3.15%, P <0.01; ADSC: 5 ± 3.55%, P = NS; membrane: 0.4 ± 4.28%, P = NS; medium: 3.7 ± 3.47%, P = NS). Also, the analysis of the mechanical behaviour of the heart tissue by stress-extension tests showed a similar behaviour in the transplanted hearts with the ADSC cellularized membrane and the healthy hearts (E: 0.085 ± 0.050 MPa and 0.070 ± 0.016 MPa, respectively, P = NS). Functional improvement was not detected in control groups treated with media or non-cellularized membranes and neither with injected ADSC cells. Furthermore, this improvement was associated with a significant decrease of the fibrosis and an increase in the revascularization degree of the heart tissue. Finally, by histological studies we confirmed a significantly greater engraftment of the cells transplanted with than without the membrane. In summary, this study has confirmed the beneficial effect of the transplant of ADSC cells previously seeded on a membrane, which improves graft survival and the homogeneous distribution of the cells in the tissue and ultimately, a more powerful paracrine effect, which is in turn reflected in a functional improvement and a positive remodelling of the infarcted heart in the chronic myocardial infarction model.