Portal de investigación
Derivation of healthy hepatocyte-like cells from a female patient with ornithine transcarbamylase deficiency through X-inactivation selection.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Wuestefeld T
Grupos
Abstract
Autologous cell replacement therapy for inherited metabolic disorders requires the correction of the underlying genetic mutation in patient's cells. An unexplored alternative for females affected from X-linked diseases is the clonal selection of cells randomly silencing the X-chromosome containing the mutant allele, without in vivo or ex vivo genome editing. In this report, we have isolated dermal fibroblasts from a female patient affected of ornithine transcarbamylase deficiency and obtained clones based on inactivation status of either maternally or paternally inherited X chromosome, followed by differentiation to hepatocytes. Hepatocyte-like cells derived from these clones display indistinct features characteristic of hepatocytes, but express either the mutant or wild type OTC allele depending on X-inactivation pattern. When clonally derived hepatocyte-like cells were transplanted into FRG(®) KO mice, they were able to colonize the liver and recapitulate OTC-dependent phenotype conditioned by X-chromosome inactivation pattern. This approach opens new strategies for cell therapy of X-linked metabolic diseases and experimental in vitro models for drug development for such diseases.
© 2022. The Author(s).
Datos de la publicación
- ISSN/ISSNe:
- 2045-2322, 2045-2322
- Tipo:
- Article
- Páginas:
- 2308-2308
- PubMed:
- 35145162
- Factor de Impacto:
- 1,005 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
SCIENTIFIC REPORTS NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 1
Documentos
- No hay documentos
Filiaciones
Keywords
- OTC DEFICIENCY; INBORN-ERRORS; GENE; METABOLISM; PHENOTYPE; MUTATION; MOUSE; TRANSPLANTATION; FIBROBLASTS; PHOSPHATE
Campos de Estudio
Cita
SANTAMARIA R,BALLESTER M,GARCIA G,MARTINEZ F,BLAZQUEZ M,RIBES C,CASTELL JV,Wuestefeld T,BORT R. Derivation of healthy hepatocyte-like cells from a female patient with ornithine transcarbamylase deficiency through X-inactivation selection. Sci Rep. 2022. 12. (1):p. 2308-2308. IF:4,600. (2).