Keratinocyte cell lines derived from severe generalized recessive E pidermolysis B ullosa patients carrying a highly recurrent COL 7A1 homozygous mutation: models to assess cell and gene therapies in vitro and in vivo

Abstract Recessive dystrophic epidermolysis bullosa ( RDEB ) is caused by deficiency of type VII collagen due to COL 7A1 mutations such as c.6527insC, recurrently found in the S panish RDEB population. Assessment of clonal correction–based therapeutic approaches for RDEB requires large expansions of...

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Published in:Experimental dermatology 2013-09, Vol.22 (9), p.601-603
Main Authors: Chamorro, Cristina, Almarza, David, Duarte, Blanca, Llames, Sara G., Murillas, Rodolfo, García, Marta, Cigudosa, Juan C., Espinosa‐Hevia, Luis, Escámez, Maria José, Mencía, Ángeles, Meana, Álvaro, García‐Escudero, Ramón, Moro, Rosa, Conti, Claudio J., Del Río, Marcela, Larcher, Fernando
Format: Article
Language:English
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Summary:Abstract Recessive dystrophic epidermolysis bullosa ( RDEB ) is caused by deficiency of type VII collagen due to COL 7A1 mutations such as c.6527insC, recurrently found in the S panish RDEB population. Assessment of clonal correction–based therapeutic approaches for RDEB requires large expansions of cells, exceeding the replication capacity of human primary keratinocytes. Thus, immortalized RDEB cells with enhanced proliferative abilities would be valuable. Using either the SV 40 large T antigen or papillomavirus HPV 16‐derived E6‐E7 proteins, we immortalized and cloned RDEB keratinocytes carrying the c.6527insC mutation. Clones exhibited high proliferative and colony‐forming features. Cytogenetic analysis revealed important differences between T antigen‐driven and E 6‐ E 7‐driven immortalization. Immortalized cells responded to differentiation stimuli and were competent for epidermal regeneration and recapitulation of the blistering RDEB phenotype in vivo . These features make these cell lines useful to test novel therapeutic approaches including those aimed at editing mutant COL 7A1 .
ISSN:0906-6705
1600-0625
DOI:10.1111/exd.12203