In the news

It has been a good year for stem cells. Following the Nobel Prize for Physiology and Medicine (see previous news article), and the production of stem cells from human skin (see previous news article), scientists have now provided a conclusive demonstration of their huge therapeutic potential. Reported in the online advanced edition of Science, a humanized sickle cell anaemia mouse model has been successfully treated with a combination of gene and cell therapy [Hanna J. et al (2007) Science doi: 10.1126/science.1152092].

 

The method follows on from a series of studies showing that human, monkey and mouse skin cells can be developmentally reprogrammed in vitro into induced pluripotent stem cells (iPS), by using a retrovirus to insert four transcription factor genes into the cells. These cells have the capacity to differentiate into any of the specialised cell types present in the body. The cells can also be genetically reprogrammed in vitro using gene therapy in order to correct any disease causing mutations, and then differentiated into the appropriate cell type before transplantation back into the patient. As these cells can be taken from the patient, they have huge potential for therapeutic use by avoiding issues of immune-mediated tissue rejection.

 

The technique was tested on so-called ‘knock-in’ mice, in which mouse haemoglobin genes were replaced with human counterparts, with the homozygous sickle cell anaemia variant that causes the mice to exhibit typical symptoms of the disease. Skin cells were removed from the mice and reprogrammed into iPS. The sickle cell mutation in the genome of these cells was then corrected by gene targeting, and the cells differentiated into haematopoetic (blood) progenitor cells before being transplanted back into the mice. After 12 weeks, around 70% of the peripheral blood cells present in the mice were derived from these iPS cells and the red blood cell count had returned to within the normal range with significantly fewer misshapen cells. Problems with renal function associated with sickle cell anaemia were also substantially ameliorated by the treatment.

 

Comment: This study underlines the therapeutic potential of stem cells combined with gene therapy, whilst avoiding any tricky ethical entanglements by using iPS instead of embryonic stem cells. However, before this technology can be trialled in humans, the technique must be refined to avoid using an oncogene (c-Myc) for reprogramming and a retrovirus for introducing the transcription factors genes, in order to lessen the risk of cancer with the current approach.