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The multidrug resistance protein breast cancer resistance protein (BCRP) protects adipose-derived stem cells against ischemic damage

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Abstract

Adipose tissue-derived stem cells (ASCs) are promising candidates for regenerative therapy, like after myocardial infarction. However, when transplanted into the infarcted heart, ASCs are jeopardized by the ischemic environment. Interestingly, it has been shown that multidrug resistance (MDR) proteins like the breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) have a protective effect in haematopoietic stem cells. In ASC, however, only expression of BCRP was shown until now. In this study, we therefore analysed the expression and functional activity of BCRP and P-gp and their putative function in ischemia in ASC. BCRP and P-gp protein expression was studied over time (passages 2–6) using western blot analysis and immunohistochemical staining. MDR activity was analysed using protein-specific substrate extrusion assays. Ischemia was induced using metabolic inhibition. All analyses demonstrated protein expression and activity of BCRP in ASCs. In contrast, only minor expression of P-gp was found, without functional activity. BCRP expression was most prominent in early passage ASCs (p2) and decreased during culture. Finally, ischemia induced expression of BCRP. In addition, when BCRP was blocked, a significant increase in dead ASCs was found already after 1 h of ischemia. In conclusion, ASCs expressed BCRP, especially in early passages. In addition, we now show for the first time that BCRP protects ASCs against ischemia-induced cell death. These data therefore indicate that for transplantation of ASCs in an ischemic environment, like myocardial infarction, the optimal stem cell protective effect of BCRP theoretically will be achieved with early culture passages ASCs.

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Authors and Affiliations

  1. Department of Pathology, VU University Medical Centre, Amsterdam, the Netherlands

    A. van Dijk, B. A. Naaijkens, G. L. Scheffer, J. Kassies, J. Aznou, M. Brouwer, F. J. van Milligen & H. W. M. Niessen

  2. Department of Plastic Surgery, VU University Medical Centre, Amsterdam, the Netherlands

    W. J. F. M. Jurgens

  3. Department of Rheumatology, VU University Medical Centre, Amsterdam, the Netherlands

    R. Oerlemans

  4. Department of Cardiology, VU University Medical Centre, Amsterdam, the Netherlands

    A. C. van Rossum

  5. Department of Hematology, VU University Medical Centre, Amsterdam, the Netherlands

    G. J. Schuurhuis

  6. Department of Cardiac Surgery, VU University Medical Centre, Amsterdam, the Netherlands

    H. W. M. Niessen

  7. ICaR-VU, Institute of Cardiovascular Research, VU University Medical Centre, Amsterdam, the Netherlands

    A. van Dijk, B. A. Naaijkens, A. C. van Rossum & H. W. M. Niessen

  8. ICIN, Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands

    B. A. Naaijkens

  9. Technology Foundation STW, Utrecht, the Netherlands

    A. van Dijk & B. A. Naaijkens

  10. Department of Pathology, ICaR-VU, VU University Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands

    A. van Dijk

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  1. A. van Dijk
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  2. B. A. Naaijkens
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  12. H. W. M. Niessen
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Correspondence to A. van Dijk.

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van Dijk, A., Naaijkens, B.A., Jurgens, W.J.F.M. et al. The multidrug resistance protein breast cancer resistance protein (BCRP) protects adipose-derived stem cells against ischemic damage. Cell Biol Toxicol 28, 303–315 (2012). https://doi.org/10.1007/s10565-012-9225-y

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  • DOI: https://doi.org/10.1007/s10565-012-9225-y

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