International Journal of Hematology

, Volume 107, Issue 3, pp 286–296 | Cite as

Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal stem cells derived from menstrual blood, bone marrow and adipose tissue

  • Irina Kozhukharova
  • Victoria Zemelko
  • Zoya Kovaleva
  • Larisa Alekseenko
  • Olga Lyublinskaya
  • Nikolay Nikolsky
Original Article


Doxorubicin (Dox) is an effective anticancer drug with known activity against a wide spectrum of malignancies, hematologic malignancies in particular. Despite extensive clinical use, the mechanisms of its side effects and negative action on normal cells remain under study. The aim of this study was to investigate the effect of Dox on cultured human mesenchymal stem cells (MSCs) derived from menstrual blood (eMSCs), bone marrow (BMSCs) and adipose tissue (AMSCs). Dox treatment in high doses decreased the survival of MSCs in a dose-dependent manner. Clinically relevant low doses of Dox induced premature senescence of eMSCs, BMSCs and AMSCs, but did not kill the cells. Dox caused cell cycle arrest and formation of γ-H2AX foci, and increased the number of SA-β-gal-positive cells. BMSCs entered premature senescence earlier than other MSCs. It has been reported that neural-like cells differentiated from MSCs of various origins are more sensitive to Dox than their parent cells. Dox-treated differentiated MSCs exhibited lower viability and earlier generation of γ-H2AX foci. Dox administration inhibited secretory activity in neural-like cells. These findings suggest that a clinically relevant Dox dose damages cultured MSCs, inducing their premature senescence. MSCs are more resistant to this damage than differentiated cells.


Doxorubicin Mesenchymal stem cells Stress-induced premature senescence γ-H2AX foci 





Mesenchymal stem cells


Bone marrow mesenchymal stem cells


Adipose mesenchymal stem cells


Endometrium from menstrual blood mesenchymal stem cells


Brain-derived neurotrophic factor

SA- β-gal

Senescence-associated β galactosidase


Fluorescence-activated cell system


Enzyme-linked immunosorbent assay


Neuronal nuclear antigen


Glial fibrillary acidic protein


Standard deviation


Basic fibroblast growth factor


Epidermal growth factor


Senescence-associated secretory phenotype


Stress-induced premature senescence



We thank Dr. Maxim Puzanov (Federal Almazov Medical Research Centre, Saint-Petersburg) for providing human bone marrow and adipose stem cell lines. We thank Dr. Irina Fridlyanskaya for critical revision of the manuscript. The work was supported by the Russian Science Foundation (Project 14-50-00068).

Compliance with ethical standards

Ethical approval

The study was performed according to the Helsinki Declaration and approved by the “Ethics Committee of Federal Almazov Medical Research Centre”, Saint-Petersburg, Russia.

Conflict of interest

The authors declare that they have no conflict of interests.


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  1. 1.Department of Intracellular Signaling and TransportInstitute of Cytology Russian Academy of SciencesSaint-PetersburgRussia

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