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Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Cell and Tissue Research volume 336, pages 465–475 (2009)Cite this article

Abstract

Little information is available concerning multidrug resistance (MDR) in mesenchymal stem cells, although several studies have reported that MDR is associated with hyaluronan in neoplastic cells. We have evaluated whether a hyaluronan-coated surface modulates MDR in placenta-derived human mesenchymal stem cells (PDMSCs). We have found that PDMSCs cultured on a tissue-culture polystyrene surface coated with 30 μg/cm2 hyaluronan are more resistant than control PDMSCs to doxorubicin. Inhibiting PI3K/Akt signaling has shown that the PI3K/Akt pathway modulates both P-glycoprotein activity and doxorubicin resistance. In addition, 10 μM verapamil dramatically suppresses the doxorubicin resistance induced by the hyaluronan-coated surface, indicating that P-glycoprotein activity is necessary for MDR. We have further found that PDMSCs treated with CD44 small interfering RNA (siRNA) and grown on a polystyrene surface coated with 30 μg/cm2 hyaluronan have fewer P-glycoprotein+ cells and lower CD44 expression levels (less than 60% in both cases) than PDMSCs not treated with CD44 siRNA and grown on the hyaluronan-coated surface. Moreover, treatment with CD44 siRNA suppresses the hyaluronan-substratum-induced doxorubicin resistance. We conclude that a hyaluronan substratum induces MDR in PDMSCs through CD44 signaling.

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Affiliations

  1. Institute of Biotechnology, National Cheng Kung University, 1 University Road, Tainan, 70101, Taiwan

    Chi-Mou Liu & Lynn L. H. Huang

  2. Department of Obstetrics and Gynecology, National Cheng Kung University, Tainan, Taiwan

    Chiung-Hsin Chang, Chen-Hsiang Yu & Chao-Chin Hsu

  3. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Lynn L. H. Huang

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  1. Chi-Mou Liu
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  2. Chiung-Hsin Chang
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  3. Chen-Hsiang Yu
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  4. Chao-Chin Hsu
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  5. Lynn L. H. Huang
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Correspondence to Lynn L. H. Huang.

Additional information

This work was supported by research grant NSC95–2745-B-006–003-MY2 from the National Science Council, Taiwan, and by Landmark Project Grant A25, funded by the Taiwan Ministry of Education, from National Cheng Kung University.

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Liu, CM., Chang, CH., Yu, CH. et al. Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling. Cell Tissue Res 336, 465–475 (2009). https://doi.org/10.1007/s00441-009-0780-3

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  • DOI: https://doi.org/10.1007/s00441-009-0780-3

Keywords

  • Hyaluronan
  • Mesenchymal stem cells
  • CD44
  • Multidrug resistance
  • P-glycoprotein
  • Human