Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin

Science. 2007 Dec 21;318(5858):1920-3. doi: 10.1126/science.1152092. Epub 2007 Dec 6.


It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell-like state by introducing combinations of four transcription factors. However, the therapeutic potential of such induced pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell anemia mouse model, we show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. Our results provide proof of principle for using transcription factor-induced reprogramming combined with gene and cell therapy for disease treatment in mice. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / physiopathology
  • Anemia, Sickle Cell / therapy*
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cellular Reprogramming*
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Embryonic Stem Cells / cytology
  • Erythrocyte Count
  • Fibroblasts / cytology*
  • Genes, myc
  • Globins / genetics
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology*
  • Hemoglobin A / analysis
  • Hemoglobin, Sickle / analysis
  • Humans
  • Kidney Concentrating Ability
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Male
  • Mice
  • Octamer Transcription Factor-3 / genetics
  • Pluripotent Stem Cells / cytology*
  • SOXB1 Transcription Factors
  • Trans-Activators / genetics
  • Transduction, Genetic


  • DNA-Binding Proteins
  • Hemoglobin, Sickle
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Trans-Activators
  • Globins
  • Hemoglobin A