Mukherjee, S;
Santilli, G;
Blundell, MP;
Navarro, S;
Bueren, JA;
Thrasher, AJ;
(2011)
Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells.
PLOS ONE
, 6
(3)
, Article e17565. 10.1371/journal.pone.0017565.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Generation of Functional Neutrophils from a Mouse Model of X-Linked Chronic Granulomatous Disorder Using Induced Pluripotent Stem Cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0017565 |
| Publisher version: | http://dx.doi.org/ |
| Language: | English |
| Additional information: | © 2011 Mukherjee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by generous funding from the following: European Program "7FWP, Health" (PERSIST; Ref Grant Agreement no: 222878); Chronic Granulomatous Disorder Research Trust (J4G/04B/GT09); Biotechnology and Biological Sciences Research Council, UK (BB/F015526/1); Wellcome Trust (090233/Z/09/Z); GOSH Children's Charity; Ministry of Science and Innovation for Programa de Fomento de Cooperación Científica Internacional (110-90.1); Plan Nacional de Salud y Farmacia (SAF 2009-07164); Fondo de Investigaciones Sanitarias, ISCIII (Programa RETICS-RD06/0010/0015); Fundación Marcelino Botín for promoting translational research at the División de Hematopoyesis y Terapia Génica at the CIEMAT-CIBERER. CIBERER is an initiative of the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | HEMATOPOIETIC LINEAGES, EFFICIENT PRODUCTION, DEFINED FACTORS, GENE-THERAPY, DISEASE, FIBROBLASTS, PROGENITORS, ACTIVATION, INDUCTION, CULTURE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1301688 |
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