Regenerative Medicine Research最新文献

Background: Alcoholic cardiomyopathy (CMP) is one of the major complications of chronic excessive alcohol consumption. The pathogenic mechanisms implicated are diverse, inducing functional and structural changes in the myocardium. Insulin-like Growth Factor 1 (IGF-1) plays an important role in modulating the cell cycle, and helps the differentiation and proliferation of cardiac tissue inhibiting apoptosis. Experimental studies have suggested the role of IGF-1 in alcohol-induced cardiac damage. The aim of the present study was to determine the effect of chronic alcohol consumption on IGF-1 myocardial expression and to compare this expression in cases of hypertension and other cardiac diseases.

Methods: We studied heart samples from human organ donors: 10 healthy donors, 16 with hypertension, 23 with chronic alcohol consumption and 7 with other causes of cardiac disease. IGF-1 myocardial expression was evaluated with a specific immunohistochemistry assay using a semi-quantitative method.

Results: A significant decrease in IGF-1 myocardial expression was observed comparing all the cases included with control donors. This decrease in IGF-1 myocardial expression was significantly lower in the group of donors with chronic alcohol consumption compared to controls. On group evaluation according to the presence of CMP, donors with chronic alcohol consumption without CMP presented significantly lower IGF-1 expression than controls, whereas donors with chronic alcohol consumption with CMP showed a downward trend without achieving significance.

Conclusions: Chronic alcohol consumption significantly reduces IGF-1 myocardial expression. This decrease induced by alcohol is partially compensated in the presence of structural myocardial damage.

In tissues characterized by a high turnover or following acute injury, regeneration replaces damaged cells and is involved in adaptation to external cues, leading to homeostasis of many tissues during adult life. An understanding of the mechanics underlying tissue regeneration is highly relevant to regenerative medicine-based interventions. In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization. Epidermis is a stratified squamous epithelium that migrates from the edge of the wound on the underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells whose neurites are organized in bundles, within an endoneurium of connective tissue; they either die upon injury or undergo remodeling and axon regrowth. Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle fibers, that can temporarily survive in broken pieces; satellite cells residing along the fibers form new fibers, which ultimately fuse with the old ones as well as with each other to restore the previous organization. Satellite cell asymmetrical division grants a reservoir of undifferentiated cells, while other stem cell populations of muscle and non-muscle origin participate in muscle renewal. Following damage, all the tissues analyzed here go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms.