Developing new cell models

Professor Lyle Armstrong and collaborators will generate stem cell lines from people with CGD as valuable tools to speed up CGD research.  Awarded in September 2009.

Project leaders: Prof Lyle Armstrong, Prof Majlinda Lako, Prof William James and Prof Reinhard Seger
Locations: Research Fellow employed on project: Dr Y Jiang
Institute of Human Genetics and The North East England Stem Cell Institute, Newcastle University; Sir William Dunn School of Pathology, University of Oxford and University Children’s Hospital, Zurich
Duration: 2 years
Total project cost: £145,369, with a generous donation of £30,347 from the Belron World Conference Foundation
Official title: Using Induced Pluripotent Stem Cell Technology to Model Human CGD Disease

There are currently few models with which to study human CGD. This project, at the cutting edge of scientific advances, will generate new CGD cell models.  Skin cells from people with CGD will be reprogrammed in the laboratory using key genetic triggers that turn back their biological clock so they become stem cells capable of generating many different cell types including the white blood cells affected in CGD.  These cells called induced pluripotent stem cells or iPSC can be grown up in unlimited numbers in the laboratory for use in research and in the future, for treating patients.

The cell lines generated, carrying different CGD defects, will have real advantages for studying the biology of CGD and can be used as screening tools for drugs and testing gene therapy methods. Once generated the cell lines will be made available for all researchers to use through storage in a public stem cell bank.

What this research means to people with CGD 

  • Allow testing of new gene therapy tools and methods for the cure of CGD
  • By combining iPSC technology with gene therapy it may be possible in the future to repair the genetic defect in iPSCs developed from people with CGD and grow these up to produce unlimited numbers of healthy blood cells capable of fighting infection. These cells would be genetically matched to the patient and could be given back to patients without the risk of rejection
  • Accelerate the drug discovery process by having a large source of relevant cells available to screen drugs that might better treat the complications of CGD
  • Enable better understanding of the biological consequences of CGD on the working of the cell
  • Unlock the secrets of CGD that could potentially shed light on other conditions such as inflammation
  • Create robust, cost effective and replicable human cell models of all types of CGD that will be available to researchers around the world to speed up research into CGD
  • Foster international collaboration that will benefit people with CGD all around the world

Background information

The first reports of the development of mouse iPSCs were in 2006 followed by reports of human cell lines in 2007.  iPSCs are already useful tools for drug development and modelling of diseases, and scientists hope to use them in transplantation medicine. 

Although using iPSC cells as a therapy in humans is far in the future recent work has demonstrated their potential as a new therapy for disease.  Work at the National Institutes of Health in the USA showed that they could reprogramme human iPSCs to retinal cells  (the cells in the eye that capture light and help us see). When these cells were transplanted into the eye of a rat model of retinal degeneration the newly, transplanted retinal cells functioned normally and resulted in long-term preservation of vision. 

Further information and links

Method of the Year 2009: iPS cells - www.youtube.com/watch?v=fGNchPdlaGU&feature=related