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Medicine regenerative in epithelial tissue

The integrity and repair of the epithelia of coating depend on a population of stem cells present in the basal layer and in specific niches. Epithelial stem cells generate a population of progenitors with limited proliferative capacity that give rise to terminally differentiated cells. In the stratified human epithelia have been identified and isolated three types of keratinocytes with different proliferative capacity: holoclone, meroclone and paraclone (Barrandon and Green, PNAS 1987). The oloclone are stem cells of epithelia of coating and have been characterized at the molecular level (De Luca et al., PNAS 1990; Marchisio et al., J. Cell Biol. 1991; Zambruno et al., J. Cell Biol. 1995 ; Pellegrini et al., J. Cell Biol. 1999; Dellambra et al., 2000; Pellegrini et al., PNAS 2001; Di Iorio et al., PNAS 2005; Barbaro et al., J. Cell Biol. 2007). The holoclone possess all the characteristics of adult stem cells, such as self-renewal, proliferative capacity, telomerase activity and ability to generate all the elements of the tissue of origin. The meroclone and paraclone have the characteristics of the progenitors transients.

In recent years, knowledge of the biology of holoclone has allowed their application in clinical activity in protocols of personalized regenerative medicine and cell therapy and gene therapy (reviewed in De Luca et al., Regen. Med 2006 ; Pellegrini et al., J. Pathol. 2009; Pellegrini et al., Trends Mol. Med 2011). In particular, stem cells of coating epithelia were applied (i) in the lifesaving treatment of third degree burns (Pellegrini et al., Transplantation 1999), stable vitiligo (Guerra et al., Arch Dermatol. 2000; Guerra et al., Br J. Dermatolol. 2004) and chronic ulcers of the lower limbs, (ii) in the first reconstruction of the corneal epithelium in deficit of corneal stem cells with recovery of visual acuity in eyes not otherwise curable (Pellegrini et al., Lancet 1997; Rama et al., Transplantation 2001; Rama et al., N. Eng J. Med 2010),

(iii)       in the first retread urethral epithelium in the posterior hypospadias congenital (Romagnoli et al., N. Eng J. Med . 1990), (iv) in the first clinical trial of ex vivo gene therapy of junctional epidermolysis bullosa (Mathor et al., PNAS 1996; Dellambra et al., 1998; Mavilio et al., Nat. Med 2006). The clinical applications of cultured epidermal stem cells and limbal cell therapy of burns, skin or eyes that are advanced therapies consolidated.

The clinical applications of genetically modified stem cells urethral and of those epidermal are still in clinical trials.

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