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Small molecules in stem cell self-renewal and differentiation

Gene Therapy volume 15, pages 126–135 (2008)Cite this article

Abstract

The use of stem cells in regenerative medicine is a promising approach to the treatment of disease and injury. Natural and synthetic small molecules have been shown to be useful chemical tools for controlling and manipulating the fates of cells. Small molecules can target signaling transduction pathways (for example, tyrosine kinase receptors) and affect DNA replication, cell differentiation, tumor metastasis and apoptosis. Stem cells share many properties with cancer cells and these similarities can provide insights to control and direct cell behavior; small molecules are already standard chemotherapeutics in the treatment of cancer. Libraries of small molecules have been examined for anticancer behavior (especially apoptosis), and, more recently, for stem cell self-renewal and differentiation capabilities in potential approaches to regenerative medicine. Differentiation therapy for cancer is based on the idea that cancer cells are undifferentiated embryonic-like cells and proposes to promote the differentiation and hence block cell proliferation. For example, retinoids have a role in stem cell differentiation to several lineages and have also been used to promote differentiation of acute promyeloic leukemic cells. Small molecules are also important tools for understanding mechanistic and developmental processes. Strategies for generating functional small molecule libraries have been outlined previously. In this review, we will look at several small molecules that have been described in the recent literature as effectors of stem cell self-renewal or differentiation as associated with the Wnt, Hedgehog or NF-κB pathways.

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Acknowledgements

The authors thank D Humiston for editorial assistance and artistic contribution for Figure 1. The authors also thank Drs J Huard and B Péault of the Stem Cell Research Center for scientific discussions. This work was supported by the Research Advisory Committee, Children's Hospital of Pittsburgh and the United States Department of Defense.

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  1. Stem Cell Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA

    R C Schugar & B M Deasy

  2. Molecular Genetics and Biochemistry Department, University of Pittsburg, Pittsburgh, PA, USA

    P D Robbins

  3. Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    B M Deasy

  4. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

    B M Deasy

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  1. R C Schugar
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Schugar, R., Robbins, P. & Deasy, B. Small molecules in stem cell self-renewal and differentiation. Gene Ther 15, 126–135 (2008). https://doi.org/10.1038/sj.gt.3303062

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