Influence of the dose of human umbilical cord mesenchymal stem cells on acute inflammation on the peritonitis model in mice

  • P. A. Pikus
  • S. E. Rymar
  • N. S. Shuvalova
  • V. A. Kordium


Aim. Study the effect of the dose of human umbilical cord MSCs on acute inflammation on the peritonitis model in mice with intraperitoneal induction of a 3% solution of proteose peptone. Human umbilical cord MSCs can be used in the cell therapy as allogeneic since their properties provide a minimal risk of an immune response with the transplantation MSCs into body. The inflammation follows all diseases and it is base target for MSCs. Methods. The study is used methods of cell biology. Results. Research has shown that 4 hours after the injection of MSCs, the number of macrophages in the peritoneal cavity of mice immediately decreased. The introduction of 5x103 cells per mouse resulted in 78% decrease the number of macrophages in the exudate. Complete return to a normal has been observed with the injection 70–100 x 103 of cells per mouse. In parallel with the decrease in the number of macrophages, their phagocytic activity has decreased, and these changes also depend on the dose of transplanted MSCs. Conclusions. A dose-dependent decrease of acute inflammation of the abdominal cavity in mice was shown with the introduction of MSCs from the human umbilical cord. The number of macrophages into peritoneal exudate has decreased by 78% in 4 hours after the injection 5x103 cells per mouse. Complete suppression of inflammation has observed with the introduction of 70–100 x 103 cells. Inhibition of inflammation is accompanied by a decrease in the phagocytic activity of macrophages, which indicates a change in their polarization.

Keywords: human umbilical cord MSCs, inflammation, macrophages, phagocytic activity.


Semenov O.V., Koestenbauer S., Riegel M., Zech N., Zimmermann R., Zisch A.H. Malek A. Multipotent mesenchymal stem cells from human placenta: Critical parameters for isolation and maintenance of stemness after isolation. Am. J. Obstet. Gyne-col. 2010. Vol. 202. P. 191–193. doi: 10.1016/j.ajog.2009.10.869.

Ilancheran S., Moodley Y., Manuelpillai U. Human fetal membranes: A source of stem cells for tissue regeneration and repair. Placenta. 2009. Vol. 30. P. 2–10. doi: 10.1016/j.placenta.2008.09.009.

Pappa K.I., Anagnou N.P. Novel sources of fetal stem cells: Where do they fit on the develop-mental continuum? Regen. Med. 2009. № 4. P. 423–433. doi: 10.2217/rme.09.12.

Marcus A.J., Woodbury D. Fetal stem cells from extra-embryonic tissues: Do not discard. J. Cell. Mol. Med. 2008. № 12. P. 730–742. doi: 10.1111/j.1582-4934.2008.00221.

Radzikowski C. Protection of animal research subjects. Sci. Eng. Ethics. 2006. Vol. 12. P. 103–110.

Caramanis V., Varonos D. The Influence of Acetylsalicylic Acid, Phenylbutazone, Indomethacin, and F1ufenamic Acid on the Kinetics Arch. Toxicol., Suppl. 1980. Vol. 4. P. 485–491.

Cain D.W., O'Koren E.G. Identification of a tissue-specific, C/EBPв-dependent pathway of differentiation for murine perito-neal macrophages. J. Immunol. 2013. Vol. 191, № 9. P. 4665–4675. doi: 10.4049/jimmunol.1300581.

Chen H.-Y., Weng I., Li Ch.-Sh., Wan L., Liu F.-T. Examination of Galectins in Phagocytosis Methods. Mol Biol. 2015. P. 201–213. doi: 10.1007/978-1-4939-1396-1_13.

Dominici M., Blanc K.L., Mueller I., Slaper-Cortenbach I., Marini F.C., Krause S., Deans R.J. A Keatin Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytother-apy. 2006. Vol. 8, № 4. Р. 315–317. doi: 10.1080/14653240600855905.

Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004. Vol. 25. P. 677–686. doi: 10.1016/

Parisi L., Gini E., Baci D., Tremolati M., Fanuli M., Bassani B. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders? J. of Immunology Research. 2018. P. 25. doi: 10.1155/2018/8917804.

Italiani P., Boraschi D. From monocytes to M1/M2 macrophages: phenotypical functional differentiation. Frontiers in immu-nology. 2014. Vol. 5. Р. 514. doi: 10.3389/fimmu.2014.00514.

Lam R.S., Brien-Simpson N.A. Holden Reynolds Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyro-monas gingivalis. PLoS ONE. 2016. Vol. 11, № 7. Р. 11–23. doi: 10.1371/journal.pone.0158629.

Eunkyung Chung Crosstalk between Mesenchymal Stem Cells and Macrophages in Tissue Repair. Tissue Engineering and Regenerative Medicine. 2014. Vol. 11, № 6. Р. 431–438. doi: 10.5114/wo.2017.68616.

Song Ji-young, Kang H.J., Hong J.S., Kim C.J., Shim J.-Y., Lee C.W., Choi J. Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by repolarizing intestinal macrophages. Scientific Reports. 2017. № 138. P. 9. doi: 10.1038/s41598-017-09827-5.

Carty B.P. Mahon The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents? Clinical and Experimental Immunology. 2017. Vol. 188. P. 1–11. doi: 10.1111/cei.12929.