Gene Therapy + Stem Cells = Great Therapeutic Potential

By Dr. Caroline Wright, Foundation for Genomics and Population Health, December 10, 2007

Scientists have now provided a conclusive demonstration of their huge therapeutic potential with the production of stem cells from human skin and the Nobel Prize for Physiology and Medicine: stem cells have had a fantastic year. A humanized sickle cell anaemia mouse model has been successfully treated with a combination of gene and cell therapy, as reported in the online advanced edition of Science.

By using a retrovirus to insert four transcription factor genes into the cells, human, monkey and mouse skin cells can be developmentally reprogrammed in vitro into induced pluripotent stem cells (iPS). Any of the specialized cell types that are present in the body can be created from the iPS cells. Using gene therapy in order to correct any disease causing mutations, the cells can also be genetically reprogrammed in vitro. Then before transplantation back into the patient, the cells can be differentiated into the appropriate cell type. By avoiding issues of immune-mediated tissue rejection since the cells are derived from the patient, the therapeutic potential is huge.

Mouse hemoglobin genes were replaced with human counterparts, with the homozygous sickle cell anaemia variant that causes the mice, which are called 'knock-in' mice, to exhibit typical symptoms of the disease. iPS cells were created with skin cells that were removed from the mice. The cells were differentiated into hematopoetic (blood) progenitor cells before being transplanted back into the mice, but first, the sickle cell mutation in the genome of these cells was then corrected by gene targeting. The red blood cell count had returned to within the normal range with significantly fewer misshapen cells after 12 weeks. The iPS cells also were responsible for for producing around 70% of the peripheral blood cells present in the mice. The treatment also substantially reduced the problems with renal function associated with sickle cell anemia.

While avoiding any tricky ethical snares by using iPS instead of embryonic stem cells, the study underlines the therapeutic potential of stem cells combined with gene therapy. With further refinement, the technology could potentially be used in humans as well.