Cell and Tissue Research

, Volume 336, Issue 3, pp 465–475

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

Authors

  • Chi-Mou Liu
    • Institute of BiotechnologyNational Cheng Kung University
  • Chiung-Hsin Chang
    • Department of Obstetrics and GynecologyNational Cheng Kung University
  • Chen-Hsiang Yu
    • Department of Obstetrics and GynecologyNational Cheng Kung University
  • Chao-Chin Hsu
    • Department of Obstetrics and GynecologyNational Cheng Kung University
    • Institute of BiotechnologyNational Cheng Kung University
    • Institute of Clinical Medicine, College of MedicineNational Cheng Kung University
Regular Article

DOI: 10.1007/s00441-009-0780-3

Cite this article as:
Liu, C., Chang, C., Yu, C. et al. Cell Tissue Res (2009) 336: 465. doi:10.1007/s00441-009-0780-3

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.

Keywords

HyaluronanMesenchymal stem cellsCD44Multidrug resistanceP-glycoproteinHuman

Copyright information

© Springer-Verlag 2009