Cell Therapy by Generation of Disease-Corrected, Patient-Specific Pluripotent Stem Cells

Abstract

Several diseases with genetic etiologies have proved to be cured by bone marrow
transplantation. However, donor availability constrains its usage. Recent technologies have
made human induced pluripotent stem (iPS) cells a foreseeable and realistic source to release
this limitation.
iPS cells derived from somatic cells hold promise to develop patient-specific cell
therapies and provide experimental platforms to model human diseases. iPS cells are the
product of somatic cell reprogramming to an embryonic-like state. Reprogramming mature
somatic cells to generate iPS cells occur by the introduction of a defined and limited set of
transcription factors. Very recently, iPS-cell technology has been successfully applied to
human somatic cells and used for the generation of disease-corrected, patient-specific cells
with potential value for stem cell therapy. The generation of patient-specific iPS cells could
be used in the treatment of several human inherited diseases especially fatal diseases
requiring haematopoietic stem cell transplantation. One of the most suitable candidates is a
disorder called Wiskott-Aldrich syndrome (WAS). WAS is an X-linked recessive disorder
characterized by immunodeficiency, thrombocytopenia and eczema. Without bone marrow
transplantation, most patients die by 10 years old due to recurrent infections, haemorrhage or
autoimmune diseases. We have identified a Thai patient with classic WAS with a novel and
unique termination codon mutation (p.X503R) in the WAS gene. This resulted in an absence
of protein with a severe phenotype in this patient. Since bone marrow transplantation cannot
be performed due to a lack of a suitably matched donor, disease-corrected, patient-specific
iPS cells could be an alternative source for treatment of this fatal disease.