Biomedical Engineering Reference
In-Depth Information
vectors can effectively transduce SC derived from a skin biopsy of junctional EB,
restore synthesis of laminin-5 in keratinocytes, and normal adhesion in vivo. Self-
inactivating lentiviral vectors could become a good alternative for the gene therapy
in junctional EB [
36
]. These studies clearly indicate the possibility of treating
other genodermatoses with gene therapy and change/save life of a huge number of
patients. To confirm this hope, a preclinical corrective gene transfer in SC from
patients with Xeroderma pigmentosum (XP) has been recently reported. XP is a
devastating skin disease associated with a high predisposition to skin cancer due to
XP cells being deficient in nucleotide excision repair (NER) and causing genome
instability. Wild-type XPC gene was transduced into SC and maintained long term
in culture. In addition, corrected XP cells displayed normal NER capacity in skin
equivalent cultures and murine model of human skin regeneration in vivo [
37
].
4.5 Vitiligo
Vitiligo is an acquired pigmentary disorder of unknown etiology that is clinically
characterized by the development of white macules related to the selective disap-
pearance or loss of function of melanocytes. Keratinocytes are essential for mela-
nocyte function, in that they release a number of factors that contribute to cell
differentiation and melanogenesis. In vitiligo, keratinocytes from involved skin
contain a high proportion of apoptotic cells [
38
], have a shorter life span, and are
unable to maintain melanocytes in vitro [
39
]. Keratinocyte and melanocyte sus-
pensions have been recently used to improve vitiligo [
40
]. Similarly to grafting
cultured keratinocytes enriched in SC in wounds, the transplantation of sheets from
cultured keratinocytes could have a potential benefit in vitiligo, given the quality of
the culture system which is based upon a high content in keratinocyte SC [
41
].
References
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Middelkoop E, Ulrich MM (2007) Culture of keratinocytes for transplantation without the
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2. Pincelli C, Marconi A (2011) Keratinocyte stem cells: friends and foes. J Cell Physiol
225(2):310-315
3. Blanpain C, Fuchs E (2006) Epidermal stem cells of the skin. Annu Rev Cell Dev Biol
22:339-373
4. Levy V, Lindon C, Harfe BD, Morgan BA (2005) Distinct stem cell populations regenerate
the follicle and interfollicular epidermis. Dev Cell 9(6):855-861
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telogen to anagen transition of murine hair follicle stem cells. J Dermatol Sci 60(3):143-150
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pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.
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