Adult stem cells in tissue homeostasis and disease: Current frontiers and perspectives in cell biology.

Stem cells (SC) are a rare population of cells characterized by the ability to self-renew in order to preserve the SC pool and to differentiate in different lineage to produce progeny needed for the physiological functions of tissues and organs. SC can be classified as embryonic SC (ESC) and adult or somatic SC (ASC): ESC have been isolated from the inner cell mass of the blastocyst and are pluripotent cells, that is cells able to differentiate into all the cell types required to form an entire organism (Smith, 2001); ASC are tissue-resident SC that, based on their differentiation potency, can be classified as multipotent, oligopotent or even unipotent. It is still controversial whether every mammalian tissue and organ possesses an ASC, but many tissue-specific ASC have been successfully identified and isolated e.g., hematopoietic stem cells (HSCs) (Baum et al., 1992; Notta et al., 2011), mammary stem cells (Stingl et al., 2006) , muscle stem cells (satellite cells) (Tedesco et al., 2010), intestinal stem cells (Barker et al., 2007), and mesenchymal stem cells (Pittenger et al., 1999). All these tissues need to constantly replace damaged or dead cells throughout the life of the animal. This process of continual cell replacement critical for the maintenance of adult tissues, is called tissue homeostasis, and is maintained through the presence of ASC (Fig. 1). The homeostatic replacement of cells varies substantially among different tissues. The epithelium of the intestine is one of the most rapidly self-renewing tissue in adult mammals and it completely self-renews in around 5 days (van der Flier L.G and Clevers H., 2009). By contrast, interfollicular epidermis takes 4 weeks to renew (Blanpain C. and Fuchs E., 2009), whereas the lung epithelium can take as long as 6 months to be replaced (XXXX). Moreover, apart from the maintenance of tissue homeostasis, ASC are devoted to the regeneration and repair of highly specialized tissues in both the plant and the animal kingdoms. Regeneration refers to the proliferation of cells to replace lost structures, such as the growth of an amputated limb in amphibians. In mammals, whole organs and complex tissues rarely regenerate after injury, but tissues with high proliferative capacity, such as the hematopoietic system and the epithelia of the skin and gastrointestinal tract, renew themselves continuously and can regenerate after injury, as long as the SC of these tissues are not destroyed (Fig. 1). Repair most often consist of a combination of regeneration and scar formation by the deposition of collagen which relative contribution depends on the ability of the tissue to regenerate and the extent of the injury. For instance, in superficial injury of the skin, wound can heal through the regeneration of the surface epithelium. However, scar formation is the predominant healing process that occurs when the extracellular matrix framework is damaged by severe injury (Fig. 1). This last mechanism results in restoration of tissue continuity but with or without function (Gurtner et al., 2008).