Skip to main content
Log in

Osteogenic Commitment of MSC Is Enhanced after Interaction with Umbilical Cord Blood Mononuclear Cells In Vitro

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

The effectiveness of stroma-dependent expansion of hematopoietic cells ex vivo may depend on the level of commitment of multipotent mesenchymal stromal cells (MSC). Markers of MSC osteodifferentiation and the level of soluble hematopoiesis regulators were determined during their interaction with umbilical cord blood mononuclears. After 72-h co-culturing, an increase in the expression of ALPL and alkaline phosphatase activity was revealed. In conditioned medium of co-cultures, the levels of osteopontin and osteoprotegerin were elevated and the levels of osteocalcin and sclerostin were reduced. Co-culturing of umbilical cord blood mononuclears with osteocommitted MSC was accompanied by more pronounced increase in the concentration of both positive (GM-CSF and G-CSF) and negative (IP-10, MIP-1α, and MCP-3) regulators of hematopoiesis. Thus, umbilical cord blood mononuclears induced the formation of early osteogenic progenitor phenotype in MSC ex vivo, providing the microenvironmental conditions necessary to support hematopoiesis. Preliminary osteocommitted MSC were more sensitive to the effect of umbilical cord blood mononuclears.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Buravkova LB, Grinakovskaya OS, Andreeva ER, Zhambalova AP, Kozionova MP. Characteristics of human lipoaspirateisolated mesenchymal stromal cells cultivated under lower oxygen tension. Cell Tissue Biol. 2009;3(1):23-28.

    Article  Google Scholar 

  2. Dmitrieva RI, Anisimov SV. Optimal protocols of hematopoietic stem cell expansion in vitro. Cell Tissue Biol. 2013;7(3):207-211.

    Article  Google Scholar 

  3. Zhambalova AP, Darevskaya AN, Kabaeva NV, Romanov YA, Buravkova LB. Specific interaction of cultured human mesenchymal and hemopoietic stem cells under conditions of reduced oxygen content. Bull. Exp. Biol. Med. 2009;147(4):525-530. doi: https://doi.org/10.1007/s10517-009-0542-y

    Article  CAS  PubMed  Google Scholar 

  4. Romanov YA, Balashova EE, Bystrykh OA, Titkov KV, Dugina TN, Kabaeva NV, Fedorova TA, Rogachevskii OV, Degtyarev DN, Sukhikh GT. Umbilical cord blood for autologous transfusion in the early postnatal ontogeny: analysis of cell composition and viability during long-term culturing. Bull. Exp. Biol. Med. 2015;158(4):523-527. doi: https://doi.org/10.1007/s10517-015-2800-5

    Article  PubMed  Google Scholar 

  5. Andreeva ER, Andrianova IV, Gornostaeva AN, Gogiya BS, Buravkova LB. Evaluation of committed and primitive cord blood progenitors after expansion on adipose stromal cells. Cell Tissue Res. 2018;372(3):523-533. doi: https://doi.org/10.1007/s00441-017-2766-x

    Article  CAS  PubMed  Google Scholar 

  6. Andreeva ER, Andrianova IV, Sotnezova EV, Buravkov SV, Bobyleva PI, Romanov YA, Buravkova LB. Human adiposetissue derived stromal cells in combination with hypoxia effectively support ex vivo expansion of cord blood haematopoietic progenitors. PLoS One. 2015;10(4):e0124939. doi: https://doi.org/10.1371/journal.pone.0124939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Arai F, Suda T. Maintenance of quiescent hematopoietic stem cells in the osteoblastic niche. Ann. N.Y. Acad. Sci. 2007;1106:41-53. doi: https://doi.org/10.1196/annals.1392.005

    Article  CAS  PubMed  Google Scholar 

  8. Boyerinas B, Zafrir M, Yesilkanal A.E, Price TT, Hyjek EM, Sipkins DA. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood. 2013;121(24):4821-4831. doi: https://doi.org/10.1182/blood-2012-12-475483

  9. Broxmeyer HE. Chemokines in hematopoiesis. Curr. Opin. Hematol. 2008;15(1):49-58. doi: https://doi.org/10.1097/MOH.0b013e3282f29012

    Article  CAS  PubMed  Google Scholar 

  10. Brunstein CG, Wagner JE. Cord blood transplantation for adults. Vox Sang. 2006;91(3):195-205. doi: https://doi.org/10.1111/j.1423-0410.2006.00823.x

    Article  PubMed  Google Scholar 

  11. Dahlberg A, Delaney C, Bernstein ID. Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood. 2011;117(23):6083-6090. doi: https://doi.org/10.1182/blood-2011-01-283606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J. Bone Miner. Res. 2006;21(11):1738-1749. doi: https://doi.org/10.1359/jbmr.060810

    Article  CAS  PubMed  Google Scholar 

  13. Haylock DN, Nilsson SK. Osteopontin: a bridge between bone and blood. Br. J. Haematol. 2006;134(5):467-474. doi: https://doi.org/10.1111/j.1365-2141.2006.06218.x

    Article  CAS  PubMed  Google Scholar 

  14. Jing D, Fonseca AV, Alakel N, Fierro FA, Muller K, Bornhauser M, Ehninger G, Corbeil D, Ordemann R. Hematopoietic stem cells in co-culture with mesenchymal stromal cells — modeling the niche compartments in vitro. Haematologica. 2010;95(4):542-550. doi: https://doi.org/10.3324/haematol.2009.010736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Le PM, Andreeff M, Battula VL. Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis. Haematologica. 2018;103(12):1945-1955. doi: https://doi.org/10.3324/haematol.2018.197004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lévesque JP, Helwani FM, Winkler IG. The endosteal “osteoblastic” niche and its role in hematopoietic stem cell homing and mobilization. Leukemia. 2010;24(12):1979-1992. doi: https://doi.org/10.1038/leu.2010.214

    Article  PubMed  Google Scholar 

  17. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 2005;280(20):19883-19887. doi: https://doi.org/10.1074/jbc.M413274200

    Article  CAS  PubMed  Google Scholar 

  18. Metcalf D. Hemopoietic cytokines. Blood. 2008;111(2):485-491. doi: https://doi.org/10.1182/blood-2007-03-079681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Moser SC, van der Eerden BCJ. Osteocalcin — a versatile bone-derived hormone. Front. Endocrinol. (Lausanne). 2019;9:794. doi: https://doi.org/10.3389/fendo.2018.00794

    Article  Google Scholar 

  20. Nakamura A, Dohi Y, Akahane M, Ohgushi H, Nakajima H, Funaoka H, Takakura Y. Osteocalcin secretion as an early marker of in vitro osteogenic differentiation of rat mesenchymal stem cells. Tissue Eng. Part C Methods. 2009;15(2):169-180. doi: https://doi.org/10.1089/ten.tec.2007.0334

    Article  CAS  PubMed  Google Scholar 

  21. Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005;106(4):1232-1239. doi: https://doi.org/10.1182/blood-2004-11-4422

    Article  CAS  PubMed  Google Scholar 

  22. Omatsu Y, Sugiyama T, Kohara H, Kondoh G, Fujii N, Kohno K, Nagasawa T. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity. 2010;33(3):387-399. doi: https://doi.org/10.1016/j.immuni.2010.08.017

    Article  CAS  PubMed  Google Scholar 

  23. Pontikoglou C, Deschaseaux F, Sensebé L, Papadaki HA. Bone marrow mesenchymal stem cells: biological properties and their role in hematopoiesis and hematopoietic stem cell transplantation. Stem Cell Rev. Rep. 2011;7(3):569-589. doi: https://doi.org/10.1007/s12015-011-9228-8

    Article  PubMed  Google Scholar 

  24. Schweikle E, Baessler T, Yildirim S, Kanz L, Möhle R, Weisel KC. Osteoprotegerin positively regulates hematopoietic progenitor cells. Curr. Stem Cell Res. Ther. 2012;7(1):72-77. doi: https://doi.org/10.2174/157488812798483458

    Article  CAS  PubMed  Google Scholar 

  25. Standal T, Hjorth-Hansen H, Rasmussen T, Dahl IM, Lenhoff S, Brenne AT, Seidel C, Baykov V, Waage A, Børset M, Sundan A, Hjertner O. Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma. Haematologica. 2004;89(2):174-182.

    CAS  PubMed  Google Scholar 

  26. Sugino N, Miura Y, Yao H, Iwasa M, Fujishiro A, Fujii S, Hirai H, Takaori-Kondo A, Ichinohe T, Maekawa T. Early osteoinductive human bone marrow mesenchymal stromal/ stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles. Biochem. Biophys. Res. Commun. 2016;469(4):823-829. doi: https://doi.org/10.1016/j.bbrc.2015.12.061

    Article  CAS  PubMed  Google Scholar 

  27. Wagner W, Wein F, Roderburg C, Saffrich R, Faber A, Krause U, Schubert M, Benes V, Eckstein V, Maul H, Ho AD. Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell-cell interaction. Exp. Hematol. 2007;35(2):314-325. doi: https://doi.org/10.1016/j.exphem.2006.10.003

    Article  CAS  PubMed  Google Scholar 

  28. Wilson A, Laurenti E, Oser G, van der Wath RC, Blanco-Bose W, Jaworski M, Offner S, Dunant CF, Eshkind L, Bockamp E, Lió P, Macdonald HR, Trumpp A. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell. 2008;135(6):1118-1129. doi: https://doi.org/10.1016/j.cell.2008.10.048

    Article  CAS  PubMed  Google Scholar 

  29. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003;22(23):6267-6276. doi: https://doi.org/10.1093/emboj/cdg599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yoshihara H, Arai F, Hosokawa K, Hagiwara T, Takubo K, Nakamura Y, Gomei Y, Iwasaki H, Matsuoka S, Miyamoto K, Miyazaki H, Takahashi T, Suda T. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007;1(6):685-697. doi: https://doi.org/10.1016/j.stem.2007.10.020

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. I. Bobyleva.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 116-122, June, 2021

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andreeva, E.R., Ezdakova, M.I., Bobyleva, P.I. et al. Osteogenic Commitment of MSC Is Enhanced after Interaction with Umbilical Cord Blood Mononuclear Cells In Vitro. Bull Exp Biol Med 171, 541–546 (2021). https://doi.org/10.1007/s10517-021-05266-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-021-05266-5

Key Words

Navigation