Stem Cell Reviews and Reports

, Volume 14, Issue 6, pp 801–811 | Cite as

The Impact of Morphine on the Characteristics and Function Properties of Human Mesenchymal Stem Cells

  • Vladimir HolanEmail author
  • Kristina Cechova
  • Alena Zajicova
  • Jan Kossl
  • Barbora Hermankova
  • Pavla Bohacova
  • Michaela Hajkova
  • Magdalena Krulova
  • Petr Svoboda
  • Eliska Javorkova


Morphine is an analgesic drug therapeutically administered to relieve pain. However, this drug has numerous side effects, which include impaired healing and regeneration after injuries or tissue damages. It suggests negative effects of morphine on stem cells which are responsible for tissue regeneration. Therefore, we studied the impact of morphine on the properties and functional characteristics of human bone marrow-derived mesenchymal stem cells (MSCs). The presence of μ-, δ- and κ-opioid receptors (OR) in untreated MSCs, and the enhanced expression of OR in MSCs pretreated with proinflammatory cytokines, was demonstrated using immunoblotting and by flow cytometry. Morphine modified in a dose-dependent manner the MSC phenotype, inhibited MSC proliferation and altered the ability of MSCs to differentiate into adipocytes or osteoblasts. Furthermore, morphine rather enhanced the expression of genes for various immunoregulatory molecules in activated MSCs, but significantly inhibited the production of the vascular endothelial growth factor, hepatocyte growth factor or leukemia inhibitory factor. All of these observations are underlying the selective impact of morphine on stem cells, and offer an explanation for the mechanisms of the negative effects of opioid drugs on stem cells and regenerative processes after morphine administration or in opioid addicts.


Mesenchymal stem cells Morphine Opioid receptors Gene expression Growth factors Cytokines 



This work was supported by grants from the Grant Agency of the Czech Republic no. 17-07070S and 17-05903S, the projects LO1309 and LO1508 from the Ministry of Education, Youth and Sports of the Czech Republic, institutional support of the Institute of Physiology (RVO:6798523) and by the project SVV 244-260435 from Charles University, Prague.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vladimir Holan
    • 1
    • 2
    Email author
  • Kristina Cechova
    • 3
    • 4
  • Alena Zajicova
    • 1
  • Jan Kossl
    • 1
    • 2
  • Barbora Hermankova
    • 1
    • 2
  • Pavla Bohacova
    • 1
    • 2
  • Michaela Hajkova
    • 1
    • 2
  • Magdalena Krulova
    • 1
    • 2
  • Petr Svoboda
    • 3
  • Eliska Javorkova
    • 1
    • 2
  1. 1.Department of Transplantation ImmunologyInstitute of Experimental Medicine of the Czech Academy of SciencesPragueCzech Republic
  2. 2.Department of Cell Biology, Faculty of ScienceCharles UniversityPrague 2Czech Republic
  3. 3.Department of BiomathematicsInstitute of Physiology of the Czech Academy of SciencesPragueCzech Republic
  4. 4.Department of Biochemistry, Faculty of ScienceCharles UniversityPrague 2Czech Republic

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