The promise of induced pluripotent stem cells in research and therapy

Journal name:
Nature
Volume:
481,
Pages:
295–305
Date published:
DOI:
doi:10.1038/nature10761
Published online

Abstract

The field of stem-cell biology has been catapulted forward by the startling development of reprogramming technology. The ability to restore pluripotency to somatic cells through the ectopic co-expression of reprogramming factors has created powerful new opportunities for modelling human diseases and offers hope for personalized regenerative cell therapies. While the field is racing ahead, some researchers are pausing to evaluate whether induced pluripotent stem cells are indeed the true equivalents of embryonic stem cells and whether subtle differences between these types of cell might affect their research applications and therapeutic potential.

At a glance

Figures

  1. Morphology of pluripotent stem cell types.
    Figure 1: Morphology of pluripotent stem cell types.

    Mouse ES (a) and iPS (b) cells form dome-shaped, refractile colonies. These colonies are in contrast to the flat morphology of mouse epiblast-derived stem cells (f), which resemble human ES (d) and iPS (e) cells. Human iPS cells induced into a naive pluripotent state by treatment with chemical inhibitors97, 98, 99, 100 (c) parallel the morphology of mouse ES and iPS cells. Scale bars, 50 μm.

  2. Medical applications of iPS cells.
    Figure 2: Medical applications of iPS cells.

    Reprogramming technology and iPS cells have the potential to be used to model and treat human disease. In this example, the patient has a neurodegenerative disorder. Patient-specific iPS cells — in this case derived by ectopic co-expression of transcription factors in cells isolated from a skin biopsy — can be used in one of two pathways. In cases in which the disease-causing mutation is known (for example, familial Parkinson's disease), gene targeting could be used to repair the DNA sequence (right). The gene-corrected patient-specific iPS cells would then undergo directed differentiation into the affected neuronal subtype (for example, midbrain dopaminergic neurons) and be transplanted into the patient's brain (to engraft the nigrostriatal axis). Alternatively, directed differentiation of the patient-specific iPS cells into the affected neuronal subtype (left) will allow the patient's disease to be modelled in vitro, and potential drugs can be screened, aiding in the discovery of novel therapeutic compounds.

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Affiliations

  1. Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana Farber Cancer Institute, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.

    • Daisy A. Robinton &
    • George Q. Daley
  2. Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.

    • Daisy A. Robinton &
    • George Q. Daley
  3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Daisy A. Robinton &
    • George Q. Daley
  4. Broad Institute, Cambridge, Massachusetts 02142, USA.

    • Daisy A. Robinton &
    • George Q. Daley
  5. Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.

    • Daisy A. Robinton &
    • George Q. Daley

Competing financial interests

G.Q.D. is a member of the scientific advisory boards and holds stock in, or receives consulting fees from, the following companies: Johnson & Johnson, Verastem, Epizyme, iPierian, Solasia Pharma and MPM Capital.

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