Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa.

[dystrophic epidermolysis bullosa]

Spontaneous reversion of disease-causing mutations has been observed in some genetic disorders . In our clinical observations of severe generalized recessive dystrophic epidermolysis bullosa (RDEB ), a currently incurable blistering genodermatosis caused by loss -of-function mutations in COL 7 A 1 that results in a deficit of type VII collagen (C 7 ), we have observed patches of healthy-appearing skin on some individuals . When biopsied , this skin revealed somatic mosaicism resulting in the self-correction of C 7 deficiency . We believe this source of cells could represent an opportunity for translational 'natural ' gene therapy . We show that revertant RDEB keratinocytes expressing functional C 7 can be reprogrammed into induced pluripotent stem cells (iPSCs ) and that self-corrected RDEB iPSCs can be induced to differentiate into either epidermal or hematopoietic cell populations . Our results give proof-of-principle that an inexhaustible supply of functional patient-specific revertant cells can be obtained--potentially relevant to local wound therapy and systemic hematopoietic cell transplantation . This technology may also avoid some of the major limitations of other cell therapy strategies , e .g ., immune rejection and insertional mutagenesis , which are associated with viral- and nonviral-mediated gene therapy . We believe this approach should be the starting point for autologous cellular therapies using 'natural ' gene therapy in RDEB and other diseases .

Diseases
Validation

Diseases presenting "mutations in col7a1" symptom

dystrophic epidermolysis bullosa

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