Generation of functional neutrophils from a mouse model of X-linked chronic granulomatous disorder using induced pluripotent stem cells

Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC). Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD), and...

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Bibliographic Details
Published in:PloS one 2011-03, Vol.6 (3), p.e17565-e17565
Main Authors: Mukherjee, Sayandip, Santilli, Giorgia, Blundell, Michael P, Navarro, Susana, Bueren, Juan A, Thrasher, Adrian J
Format: Article
Language:English
Subjects:
Animal models
Animals
Autografts
Biology
Cell Differentiation
Cell Lineage
Cellular Reprogramming - genetics
Childrens health
Chronic granulomatous disease
Cloning
Differentiation
Disease Models, Animal
DNA methylation
Embryos
Epigenetics
Expression vectors
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - pathology
Gene therapy
Gene transfer
Genes, X-Linked - genetics
Genetic disorders
Genetic vectors
Genetic Vectors - genetics
Granulomatous Disease, Chronic - pathology
Granulomatous Disease, Chronic - therapy
Health aspects
Hematopoietic stem cells
Humans
Induced Pluripotent Stem Cells - cytology
Inhibitory postsynaptic potentials
Kinases
Lentivirus - genetics
Leukocytes (neutrophilic)
Medical research
Mice
Morphology
Mutation
NAD(P)H oxidase
Neutrophils
Neutrophils - cytology
Oxidases
Phenotype
Phosphatase
Pluripotency
Stem cell transplantation
Stem cells
Viral genetics
X chromosome
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Summary:Murine models of human genetic disorders provide a valuable tool for investigating the scope for application of induced pluripotent stem cells (iPSC). Here we present a proof-of-concept study to demonstrate generation of iPSC from a mouse model of X-linked chronic granulomatous disease (X-CGD), and their successful differentiation into haematopoietic progenitors of the myeloid lineage. We further demonstrate that additive gene transfer using lentiviral vectors encoding gp91(phox) is capable of restoring NADPH-oxidase activity in mature neutrophils derived from X-CGD iPSC. In the longer term, correction of iPSC from human patients with CGD has therapeutic potential not only through generation of transplantable haematopoietic stem cells, but also through production of large numbers of autologous functional neutrophils.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0017565