oa Editorial [Hot Topic: Stem Cells and Tissue Regeneration (Executive Guest Editor: Roberta Di Pietro)]

Mankind has been always fascinated by the promise of longevity, immortality and rejuvenation. Both in Greek and in Roman mythology the difference between eternal life and eternal youth is a recurrent theme and paradigmatic is the story of Tithonos, the lover of Eos, Titan of the dawn, who obtained from Zeus the boon of immortality without eternal youth. For the first time in human history science is gaining tools to slow down, stop or even reverse biological ageing. Although life is regenerative by definition, not all the tissues possess the same regenerative potential and also those that regenerate well succumb to the ravages of ageing. The discovery of stem cells and recent advances in cellular and molecular biology have led to the development of novel therapeutic strategies aimed at the regeneration of many tissues that were injured by age, trauma or disease. For many years, bone marrow-derived stem cells were the primary source of stem cells for tissue engineering applications whereas recently more accessible sources have been identified and exploited. The emerging field of regenerative medicine started as an interdisciplinary approach to heal tissue defects and relied on the doctrine of cells, biomaterial scaffolds and signalling molecules. Although we are now at a stage in which engineering a complex tissue is no longer an unachievable goal, several issues still remain to be answered before stem cell application in clinical settings. We believe that an understanding of the molecules and processes that enable stem cells to initiate self-renewal and to divide, proliferate and then differentiate to rejuvenate damaged tissues might be the key to regenerative medicine and an eventual cure for many diseases. Thus, in the attempt to give a useful contribution to translational medicine approaches, the present hot topic issue has been organized in a first part including reviews focused on aspects of stem cell biology and basic research and a second part including reviews dealing with the most advanced stem cell-based therapeutic applications. The opening paper entitled “The architectural organization of human stem cell cycle regulatory machinery” by Gary S. Stein et al. is an outstanding review on the present state of knowledge on the nuclear architecture of human embryonic stem cells [1]. The authors clearly illustrate the differences between human embryonic stem cells and somatic cells in cell cycle control mechanisms and, particularly, in histone regulatory element components localization. The minimal organization of regulatory machinery in nuclei of pluripotent stem cells is underlined as an advantage to identify crucial components of the nuclear environment to apply to a broader context of regenerative medicine and drug design. In the following article “Chromatin modification and senescence” Giovanni Di Bernardo and the group of Umberto Galderisi, President of the Italian Society of Stem Cell Research (SCR Italy), efficiently summarize the complex issue of epigenetic changes occurring during the lifespan of a cell and, consequently, of the whole individual [2]. Particular attention is paid to different chromatin remodelling factors responsible for the unique chromatin organization of undifferentiated stem cells. Moreover, chromatin changes hallmark of normal or premature ageing are clearly described throughout the paper. The theme of ageing and senescence is continued with the review “Stem cell ageing and apoptosis” authored by Stefania Fulle et al. [3]. This is a clear and extensive overview of the current knowledge on the ageing process of stem cells and on the signalling pathways leading to programmed cell death. An ample section of the review is dedicated to haematopoietic stem cells, as a model of replicative ageing, and to satellite stem cells, as a model of chronological ageing. The authors conclude remarking that in spite of the huge number of studies and reports on stem cell ageing a more precise mechanistic understanding of stem cell behaviour is needed before this knowledge can be translated into human anti-ageing therapies. Among the recently discovered molecules able to influence stem cell function and biological processes, Stefania Crippa and the group of Maurilio Sampaolesi analyze the “Role of miRNAs in muscle stem cell biology: proliferation, differentiation and death” in an updated and comprehensive review [4]. Besides providing extensive information on miRNA biogenesis and degradation, the authors underscore novel and intriguing mechanisms regulating the fate of mesodermal stem cells (cardiac/skeletal muscle switch) suggesting that this transition may be due to the impaired expression of specific miRNAs in certain degenerative cardiac disorders.....