Modeling some aspects of stem cell therapy in cardiac tissue regeneration

An acute myocardial infarction (MI) is followed by a multiphase reparative response, in which, in particular, the damaged tissue is replaced with a fibrotic scar composed of cardiac fibroblasts and collagens. This eventually leads to impaired cardiac function, bringing to adverse conse- quences such as cardiac atrophy and arrhythmogenicity In the meantime, the damaged tissue tries to recover and the immune system responds by emitting damage signals so that new cells come to the aid. These signals are the chemokines. Several studies show that stem cell therapies can help tissue repair, after an acute myocar- dial infarction and are used as an alternative to traditional pharmacological management of myocardial infarction. Stem cells have the capacity to regenerate cardiac tissue and improve the function of the damaged heart. Thus clearly the impact of the chemokines in the attraction of these cells toward the damaged area of the myocardium becomes very important. However several biological aspects are not yet completely understood and are still under in- vestigation. For example, it was not yet completely clarified if the decline in cardiac fibrosis was due to replacement of dead cardiomyocytes by the stem cells (they can divide and become special- ized cells, such as cardiomyocytes), or because of the direct effects of paracrine factors released from the transplanted stem cells on the extracellular matrix and on other cells and molecules participating to the tissue repair [1]. In this talk we present two mathematical models describing two different effects of stem cells on the damaged cardiac tissue. On the one hand we generalize a recent model [2], which describes the rebuilding of the cardiac tissue by means of the differentiation of the stem cells, which replace the dead cardiomyocytes. In the new model the chemotactic effect of the chemokines on the stem cells is taken into con- sideration. On the other hand we generalize a recent mathematical model [3], based on a system of PDEs, which describes the processes happening in the damaged area and bringing to the formation of fibrotic scars. In our new model we take into consideration the paracrine effects of the stem cells, in order to reduce the fibrotic scar and restore the functionality of the heart. For the paracrine effetcs, we follow in particular the paper [4], which proposes a mathematical model, based on ODEs, related to the stem cell therapy after myocardial infarction.