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Angiogenesis in tissue regeneration

The tissue regeneration depends closely on stimuli and on the signals arising from the microenvironment present in the tissue itself. A useful approach and less complex than the cell transplantation for the identification of new therapeutic strategies, is the mobilization of endogenous cells. This method allows to overcome the difficulties associated with the use of embryonic stem cells and / or mature. Although this approach is very promising, in order to identify therapeutic strategies for success, you need to obtain a more detailed understanding of the complex network that includes different types of cells and factors involved in the regeneration process (Bentzinger, von Maltzahn et al., 2010). In fact, the induction of activation and mobilization of endogenous stem cells also involves the study of other essential components of the tissue and cell populations that promote inflammation, regeneration, and angiogenesis (Brunelli and Rovere-Querini 2008) .

The skeletal muscle is characterized by the remarkable ability to regenerate after suffering injury or as a consequence of diseases. The regeneration is initiated by all the signals that are released by damaged fibers is that by macrophages (MPs) and leading to activation of satellite cells quiescent, that is, the primary stem cells that are among the major factors responsible for the regeneration of the muscle (Chazaud , Sonnet et al., 2003; Arnold, Henry et al., 2007; Tajbakhsh 2009). Recent studies show that the factors produced during the inflammatory process may affect the regeneration of skeletal muscle by stimulating the survival of satellite cells and / or their proliferation, highlighting the importance of the microenvironment which is capable of mediating cell mobilization satellites and the induction of muscle regeneration (Chazaud, Sonnet et al., 2003; Brunelli and Rovere-Querini 2008).

Among the aims of this project is to study the effect of modulators of angiogenesis and / or mobilization of muscle stem cells (satellite cells) in skeletal muscle regeneration, with the ultimate aim of defining new protocols of skeletal muscle regeneration, based on in vivo administration, in models of acute muscle damage, small molecules / peptides, including through the use of biomaterials. In particular, it will be analyzed the effect of a new factor, Cripto which acts as a regulator of pluripotent stem cells (Parisi, D’Andrea et al. 2003; Minchiotti 2005), and whose expression is induced in stem cells and in inflammatory cells during the early stages of muscle regeneration, as recently demonstrated in our laboratory (Guardiola et al., under review). It will also investigate the role of Cripto on migration of satellite cells. Today, in fact, the molecules and mechanisms for migration of these cells in vivo and precursors of myoblasts are, like most aspects of the physiology of satellite cells, complicated by the rarity and the leak of them all “internal tissue . E ‘therefore necessary to develop new experimental protocols, based on time-lapse microscopy, making it possible to follow the movement of satellite cells and muscle precursors directly on muscle fibers isolated.

The skeletal muscle is characterized by the remarkable ability to regenerate after suffering injury or as a consequence of diseases. The regeneration is initiated by all the signals that are released by damaged fibers is that by macrophages (MPs) and leading to activation of satellite cells quiescent, that is, the primary stem cells that are among the major factors responsible for the regeneration of skeletal muscle. Recent studies show that the factors produced during the inflammatory process may affect the regeneration of skeletal muscle by stimulating the survival of satellite cells  and / or their proliferation, highlighting  the  importance  of the  microenvironment which  is capable  of mediating cell mobilization satellites and the induction of muscle regeneration.

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