The fate of cardiac primitive cells depends on the composition of the microenvironment changing in the pathological conditions.

CD117(+) cells contributing to the cardiac cell turnover have been recently described in the adult heart, together with numerous factors that influence their characteristics in the normal and pathological conditions. It is known that the precise spatial and temporal expression of extracellular matrix proteins and their receptors is critical for proper organ formation during organogenesis. Hence, the cardiac regeneration cannot be accomplished without the involvement of extracellular matrix. The scope of the study was to evaluate the influence of fibronectin, laminin-1, laminin-2 and collagen IV on cardiac primitive CD117(+) cells isolated from human adult heart. Moreover, cardiac fibroblasts from human adult normal and pathological hearts with ischemic cardiomyopathy were isolated and cultured to obtain the natural extracellular matrix (cardiogel) in vitro. After non-enzymatic removal of fibroblasts, this substrate was used to compare the proliferation and apoptosis of CD117(+) cells in the presence of extracellular matrix typical of normal and pathological heart. Proliferation of CD117(+) cells, evaluated by BrdU incorporation, was as low as 4,4±0.9% (n=4) in the presence of albumin and reached maximum rate of 27,7±4,7% (n=4) on laminin-1 and minimum of 8,6±0,2% (n=3) on laminin-2. Apoptosis, detected in TUNEL assay, was minimum in the presence of laminin-1 (1,8±0,4%, n=4) when compared with laminin-2 (5,2±1,1%, n=4), fibronectin (9,8±2,4%, n=4) and collagen IV (15,4±2,6%, n=4). The components of cardiogel were characterized by immunofluorescence and immunoblotting. Cardiac fibroblasts from normal heart synthesized extracellular matrix rich in laminin-2, while those from the heart with chronic ischemic cardiomyopathy produced more laminin-1, fibronectin, collagen IV and tenascin C. Interestingly, when normal CD117(+) cells were cultured on the cardiogel from pathological heart, their proliferation rate was 5,7-fold higher (n=5, p<0,05) with respect to the proliferation of cardiac primitive cells on the cardiogel from normal heart. In the similar manner, although to a lesser extent, components of extracellular matrix from pathological heart diminished apoptosis rate with respect to cardiogel from normal heart. We conclude that the components of extracellular matrix, responding to the physiological changes during cardiac remodeling, influence cardiac primitive cells biology. These results should be taken into consideration when projecting stem cells transplantation in the diseased hearts, since the microenvironment may determine the fate of the injected cells.