The Altered Migration and Distribution of Systemically Administered Mesenchymal Stem Cells in Morphine-Treated Recipients

Abstract

Mesenchymal stem cells (MSCs) have the ability to migrate to the site of injury or inflammation, and to contribute to the healing process. Since patients treated with MSCs are often users of analgesic drugs, to relieve their uncomfortable pain associated with the tissue disorder, there is a possibility of negative effects of these drugs on the migration of endogenous and exogenous MSCs. Therefore, we tested the impact of acute and chronic treatment with morphine on the migration and organ distribution of exogenous adipose tissue-derived MSCs in mouse models. Firstly, we showed that the incubation of MSCs with morphine significantly reduced the expression of adhesive molecules CD44 (HCAM), CD54 (ICAM-1) and CD106 (VCAM-1) on MSCs. Using a model of systemic administration of MSCs labeled with vital dye PKH26 and by the application of flow cytometry to detect living CD45PKH26+ cells, we found a decreased number of labeled MSCs in the lung, spleen and bone marrow, and a significantly increased number of MSCs in the liver of morphine-treated recipients. A skin allograft model was used to study the effects of morphine on the migration of exogenous MSCs to the superficial wound. Intraperitoneally administered MSCs migrated preferentially to the wound site, and this migration was significantly decreased in the morphine-treated recipients. The present results showed that morphine significantly influences the distribution of exogenous MSCs in the body, and decreases their migration to the site of injury.

Graphical Abstract

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Data Availability

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Funding

This work was supported by the project No. LTAUSA18110 – Inter-Excellence from the Ministry of Education, Youth and Sports of the Czech Republic, grant No. 19-02290S from the Grant Agency of the Czech Republic, project RVO:6798523 from the Institute of Physiology and by the Charles University programs SVV 260435 and 20604315 PROGRES Q43.

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All authors contributed to this study. VH and PS designed the study, VH, BE, KP, AZ, JK, PB and JB performed the experiments, VH and PS wrote the paper, all authors read and approved the final manuscript.

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Correspondence to Vladimir Holan.

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This study did not involve human participants. The experiments with animals were approved by the local Animal Ethics Committee of the Institute of Experimental Medicine of the Czech Academy of Sciences, Prague.

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Holan, V., Echalar, B., Palacka, K. et al. The Altered Migration and Distribution of Systemically Administered Mesenchymal Stem Cells in Morphine-Treated Recipients. Stem Cell Rev and Rep (2021). https://doi.org/10.1007/s12015-021-10126-w

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Keywords

  • Mesenchymal stem cells
  • Acute and chronic morphine treatment
  • Adhesive molecules
  • Cell migration
  • Skin graft model