Abstract
The study focused on the interaction between mesenchymal stromal cells (MSCs) and monocyte-derived macrophages (MN/MPs). The interactions play an important role in MSC in vivo indirect therapeutic effects and anti-inflammatory and immunomodulatory properties. To assess the MSC effect on MN/MP functional activity, MSCs and MN/MPs were co-cultured in standard conditions (20% O2) for 6 days. Then part of MN/MP and MN/MP + MSC cultures was exposed to short-term hypoxic stress (1% O2, 24 h), while the other part was further cultured at 20% O2. In both standard conditions and hypoxia, MSCs exerted stromal activity and increased the MN/MP viability by decreasing the MN/MP portion undergoing early apoptosis. A paracrine interaction stimulated phagocytic activity of MN/MPs without affecting activity of the lysosomal compartment at 20% O2. Hypoxic stress decreased the MSC-induced phagocytic potential and lysosomal activity. An anti-inflammatory phenotype developed in MN/MPs upon their interaction with MSCs, and MN/MPs consequently better utilized their phagocytic potential in the presence of MSCs in spite of oxygen deprivation.
Similar content being viewed by others
REFERENCES
Vasandan, A., Jahnavi, S., Shashank, C., et al., Human mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism, Sci. Rep., 2016, vol. 6, p. 38308. https://doi.org/10.1038/srep38308
Kim, J. and Hematti, P., Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages, Exp. Hematol., 2009, vol. 37, no. 12, p. 1445. https://doi.org/10.1016/j.exphem.2009.09.004
Eggenhofer, E. and Hoogduijn, M.J., Mesenchymal stem cell-educated macrophages, Transplant. Res., 2012. vol. 1, p. 12. https://doi.org/10.1186/2047-1440-1-12
Francois, M., Romieu-Mourez, R., Li, M., et al., Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation, Mol. Ther., 2012, vol. 20, p. 187.
Melief, S.M., Geutskens, S.B., Fibbe, W.E., et al., Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6, Haematologica, 2013, vol. 98, p. 888.
Melief, S.M., Schrama, E., Brugman, M.H., et al., Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages, Stem Cells, 2013, vol. 31, p. 1980.
Nemeth, K., Leelahavanichkul, A., Yuen, P.S., et al., Bone marrow stromal cells attenuate sepsis via prostaglandin E (2) -dependent reprogramming of host macrophages to increase their interleukin-10 production, Nat. Med., 2009, vol. 15, p. 42.
Gonzalez-Rey, E., Anderson, P., Gonzalez, M.A., et al., Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis, Gut, 2009, vol. 58, p. 929.
Alekseeva, O.Yu., Bobyleva, P.I., and Andreeva, E.R., Phenotype and secretome of monocyte-derived macrophages interacting with mesenchymal stromal cells under conditions of hypoxic stress, Bull. Exp. Biol. Med., 2019, vol. 168, no. 1, p. 125. https://doi.org/10.1007/s10517-019-04662-2
Dominici, M., Le Blanc, K., Mueller, I., et al., Minimal criteria for defining multipotent mesenchymal stromal cells: the International Society for Cellular Therapy position statement, Cytotherapy, 2006, vol. 8, no. 4, p. 315. https://doi.org/10.1080/14653240600855905
Wlodkowic, D., Skommer, J., and Darzynkiewicz, Z., Flow cytometry-based apoptosis detection, Methods Mol. Biol., 2009, vol. 559, p. 19. https://doi.org/10.1007/978-1-60327-017-5_2
Kurynina, A.V., Erokhina, M.V., Makarevich, O.A., et al., Plasticity of human THP–1 cell phagocytic activity during macrophagic differentiation, Biochemistry (Moscow), 2018, vol. 83, no. 3, p. 200. https://doi.org/10.1134/S0006297918030021
Sugiyama, T. and Nagasawa, T., Bone marrow niches for hematopoietic stem cells and immune cells, Inflamm. Allergy Drug Targets, 2012, vol. 11, no. 3, p. 201.
Van Poll, D., Parekkadan, B., Cho, C.H., et al., Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo, Hepatology, 2008, vol. 47, no. 5, p. 1634. https://doi.org/10.1002/hep.22236
Mangan, D.F. and Wahl, S.M., Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines, J. Immunol., 1991, vol. 147, no. 10, p. 3408.
White, G.E., McNeill, E., Channon, K.M., and Greaves, D.R., Fractalkine promotes human monocyte survival via a reduction in oxidative stress, Arterioscler. Thromb. Vasc. Biol., 2014, vol. 34, no. 12, p. 2554. https://doi.org/10.1161/ATVBAHA.114.304717
Jackson, M.V., Morrison, T.J., Doherty, D.F., et al., Mitochondrial transfer via tunneling nanotubes is an important mechanism by which mesenchymal stem cells enhance macrophage phagocytosis in the in vitro and in vivo models of ARDS, Stem Cells, 2016, vol. 34, no. 8, p. 2210. https://doi.org/10.1002/stem.2372
Johnson, D.E., Ostrowski, P., Jaumouillé, V., and Grinstein, S., The position of lysosomes within the cell determines their luminal pH, J. Cell. Biol., 2016, vol. 212, no. 6, p. 677. https://doi.org/10.1083/jcb.201507112
Ceccariglia, S., Cargnoni, A., Silini, A.R., and Parolini, O., Autophagy: a potential key contributor to the therapeutic action of mesenchymal stem cells, Autophagy, 2020, vol. 16, no. 1, p. 28. https://doi.org/10.1080/15548627.2019.1630223
Hu, C., Zhao, L., Wu, D., et al., Modulating autophagy in mesenchymal stem cells effectively protects against hypoxia- or ischemia-induced injury, Stem Cell Res. Ther., 2019, vol. 10, p. 120. https://doi.org/10.1186/s13287-019-1225-x
Funding
This work was supported by the Russian Foundation for Basic Research (project no. 17-04-00942).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interests. The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human subjects performed by any of the authors.
Additional information
Translated by T. Tkacheva
Rights and permissions
About this article
Cite this article
Alekseeva, O.Y., Bobyleva, P.I. & Andreeva, E.R. Effect of Multipotent Mesenchymal Stromal Cells on Functional Activity of Monocyte-Derived Macrophages under Short-Term Hypoxic Stress in Vitro. Hum Physiol 48, 899–905 (2022). https://doi.org/10.1134/S0362119722070155
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0362119722070155