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Immunomodulatory effect of mesenchymal stem cells: Cell origin and cell quality variations

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Abstract

The immunomodulatory property of mesenchymal stem cells (MSCs) has been previously reported. Still it is unclear if this property can be affected by the cell origin and cell quality. Using primary MSCs expanded from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) of mice, we investigated whether the immunomodulatory property of MSCs varied with cell origin and cell quality (early- vs. late-passaged BM-MSCs). BM-MSCs (p1) and AD-MSCs (p1) had a typical spindle shape, but morphological changes were observed in late-passaged BM-MSCs (p6). A pathway-focused array showed that the expression of chemokine/cytokine genes varied with different cell origins and qualities. By co-culturing with spleen mononuclear cells (MNC) for 3 days, the expression of CD4 was suppressed by all types of MSCs. By contrast, the expression of CD8 was suppressed by BM-MSCs and increased by AD-MSCs. The expression ratio of CD206 to CD86 was at a comparable level after co-culture with AD-MSCs and BM-MSCs, but was lower with late-passaged BM-MSCs. AD-MSCs highly induced the release of IL6, IL-10 and TGF-β in culture medium. Compared with early-passaged BM-MSCs (p1), late-passaged BM-MSCs (p6) released less TGF-β. Our data suggests that the immunomodulatory properties of MSCs vary with cell origin and cell quality and that BM-MSCs of good quality are likely the optimal source of immunomodulation.

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References

  1. Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guina-pig bone marrow and spleen cells. Cell Prolif 3:393–403

    Article  CAS  Google Scholar 

  2. Pittenger MF (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  PubMed  Google Scholar 

  3. Gao F, Chiu SM, Motan DA et al (2016) Mesenchymal stem cells and immunomodulation: status and prospects. Cell Death Dis. https://doi.org/10.1038/cddis.2015.327

    Article  PubMed  PubMed Central  Google Scholar 

  4. Abreu SC, Antunes MA, Xisto DG et al (2017) Bone marrow, adipose, and lung tissue-derived murine mesenchymal stromal cells release different mediators and differentially affect airway and lung parenchyma in experimental asthma. Stem Cells Transl Med. https://doi.org/10.1002/sctm.16-0398

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wen L, Zhu M, Madigan MC et al (2014) Immunomodulatory effects of bone marrow-derived mesenchymal stem cells on pro-inflammatory cytokine-stimulated human corneal epithelial cells. PLoS ONE. https://doi.org/10.1371/journal.pone.0101841

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tomic S, Djokic J, Vasilijic S, Vucevic D et al (2011) Immunomodulatory properties of mesenchymal stem cells derived from dental pulp and dental follicle are susceptible to activation by toll-like receptor agonists. Stem Cells Dev. https://doi.org/10.1089/scd.2010.0145

    Article  PubMed  Google Scholar 

  7. Amable PR, Teixeira MV, Carias RB et al (2014) Gene expression and protein secretion during human mesenchymal cell differentiation into adipogenic cells. BMC Cell Biol 15:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Engela AU, Baan CC, Dor FJ et al (2012) On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation. Front Immunol. https://doi.org/10.1186/s12860-014-0046-0

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M et al (2014) Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. https://doi.org/10.4252/wjsc.v6.i5.552

    Article  PubMed  PubMed Central  Google Scholar 

  10. Anjos-Afonso F, Bonnet D (2011) Prospective identification and isolation of murine bone marrow derived multipotent mesenchymal progenitor cells. Best Pract Res Clin Haematol. https://doi.org/10.1016/j.beha.2010.11.003

    Article  PubMed  Google Scholar 

  11. Zhang L, Chan C (2010) Isolation and enrichment of rat mesenchymal stem cells (MSCs) and separation of single-colony derived MSCs. J Vis Exp. https://doi.org/10.3791/1852

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huang S, Xu L, Sun Y, Wu T et al (2015) An improved protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. J Orthop Transl. https://doi.org/10.3791/1852

    Article  Google Scholar 

  13. Yu G, Wu X, Kilroy G, Halvorsen YD et al (2011) Isolation of murine adipose-derived stem cells. Methods Mol Biol. https://doi.org/10.1007/978-1-61737-960-4_3

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ellis KM, O’Carroll DC, Lewis MD et al (2014) Neurogenic potential of dental pulp stem cells isolated from murine incisors. Stem Cell Res Ther. https://doi.org/10.1186/scrt419

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lushaj EB, Anstadt E, Haworth R et al (2011) Mesenchymal stromal cells are present in the heart and promote growth of adult stem cells in vitro. Cytotherapy. https://doi.org/10.3109/14653249.2010.529890

    Article  PubMed  Google Scholar 

  16. Kang SG, Shinojima N, Hossain A et al (2010) Isolation and perivascular localization of mesenchymal stem cells from mouse brain. Neurosurgery. https://doi.org/10.1227/01.NEU.0000377859.06219.78

    Article  PubMed  PubMed Central  Google Scholar 

  17. Strioga M, Viswanathan S, Darinskas A et al (2012) Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. https://doi.org/10.1089/scd.2011.0722

    Article  PubMed  Google Scholar 

  18. Glennie S, Soeiro I, Dyson PJ et al (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood. https://doi.org/10.1182/blood-2004-09-3696

    Article  PubMed  Google Scholar 

  19. Bach M, Schimmelpfennig C, Stolzing A (2014) Influence of murine mesenchymal stem cells on proliferation, phenotype, vitality, and cytotoxicity of murine cytokine-induced killer cells in coculture. PLoS ONE. https://doi.org/10.1371/journal.pone.0088115

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kudlik G, Hegyi B, Czibula A et al (2016) Mesenchymal stem cells promote macrophage polarization toward M2b-like cells. Exp Cell Res. https://doi.org/10.1016/j.yexcr.2016.08.022

    Article  PubMed  Google Scholar 

  21. Zhou Y, Day A, Haykal S et al (2013) Mesenchymal stromal cells augment CD4+ and CD8+ T-cell proliferation through a CCL2 pathway. Cytotherapy. https://doi.org/10.1016/j.jcyt.2013.05.009

  22. Ribeiro A, Laranjeira P, Mendes S et al (2013) Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells. Stem Cell Res Ther. https://doi.org/10.1186/scrt336

    Article  PubMed  PubMed Central  Google Scholar 

  23. Le Blanc K, Rasmusson I, Sundberg B et al (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. https://doi.org/10.1016/S0140-6736(04)16104-7

    Article  PubMed  Google Scholar 

  24. Duijvestein M, Vos AC, Roelofs H et al (2010) Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn’s disease: results of a phase I study. Gut. https://doi.org/10.1136/gut.2010.215152

  25. Gao F, Chiu SM, Motan DA et al (2016) Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. https://doi.org/10.1038/cddis.2015.327

    Article  PubMed  PubMed Central  Google Scholar 

  26. Boregowda SV, Krishnappa V, Phinney DG (2016) Isolation of mouse bone marrow mesenchymal stem cells. Methods Mol Biol. https://doi.org/10.1007/978-1-4939-3584-0_11

    Article  PubMed  Google Scholar 

  27. Baldari S, Di Rocco G, Piccoli M et al (2017) Challenges and strategies for improving the regenerative effects of mesenchymal stromal cell-based therapies. Int J Mol Sci. https://doi.org/10.3390/ijms18102087

    Article  PubMed  PubMed Central  Google Scholar 

  28. Trounson A, Thakar RG, Lomax G, Gibbons D (2011) Clinical trials for stem cell therapies. BMC Med. https://doi.org/10.1186/1741-7015-9-52

    Article  PubMed  PubMed Central  Google Scholar 

  29. Da Silva Meirelles L, Nardi NB (2003) Murine marrow-derived mesenchymal stem cell: ISolation, in vitro expansion, and characterization. Br J Haematol. https://doi.org/10.1046/j.1365-2141.2003.04669.x

    Article  Google Scholar 

  30. Peister A, Mellad JA, Larson BL et al (2004) Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Blood. https://doi.org/10.1182/blood-2003-09-3070

    Article  PubMed  Google Scholar 

  31. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. https://doi.org/10.1080/14653240600855905

    Article  PubMed  Google Scholar 

  32. Hsu PJ, Liu KJ, Chao YY et al (2015) Assessment of the immunomodulatory properties of human mesenchymal stem cells (MSCs). J Vis Exp. https://doi.org/10.3791/53265

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ivanova-Todorova E, Bochev I, Dimitrov R et al (2012) Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4 + FOXP3 + cells and increases IL-10 secretion. J Biomed Biotechnol. https://doi.org/10.1155/2012/295167

    Article  PubMed  PubMed Central  Google Scholar 

  34. Deng Y, Zhang Y, Ye L et al (2016) Umbilical cord-derived mesenchymal stem cells instruct monocytes towards an IL10-producing phenotype by secreting IL6 and HGF. Sci Rep. https://doi.org/10.1038/srep37566

    Article  PubMed  PubMed Central  Google Scholar 

  35. Puissant B, Barreau C, Bourin P et al (2016) Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol. https://doi.org/10.1111/j.1365-2141.2005.05409.x

    Article  Google Scholar 

  36. Chen PM, Liu KL, Hsu PJ et al (2014) Induction of immunomodulatory monocytes by human mesenchymal stem cell-derived hepatocyte growth factor through ERK1/2. J Leukoc Biol. https://doi.org/10.1189/jlb.3A0513-242R

    Article  PubMed  PubMed Central  Google Scholar 

  37. Ryan EJ, Bengtsson AK (2002) Immune function of the decoy receptor osteoprotegerin. Crit Rev Immunol 22:15

    Article  Google Scholar 

  38. Fan L, Hu C. Chen J, Cen P et al (2016) Interaction between mesenchymal stem cells and B-cells. Int J Mol Sci. https://doi.org/10.3390/ijms17050650

    Article  PubMed  PubMed Central  Google Scholar 

  39. Rosado MM, Bernardo ME, Scarsella M et al (2015) Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells. Stem Cells Dev. https://doi.org/10.1089/scd.2014.0155

    Article  PubMed  Google Scholar 

  40. Schlesinger M, Rabinowitz R, Levy P, Maayan S (1996) The expression of CD8 on B lymphocytes in HIV-infected individuals. Immunol Lett 50:23–27

    Article  CAS  PubMed  Google Scholar 

  41. Rabinowitz R, Massiah E, Hadar R, Schlesinger M (1995) In vitro activation leads to the binding of T-cell markers to the surface of B-lymphocytes. Clin Immunol Immunopathol 76:148–154

    Article  CAS  PubMed  Google Scholar 

  42. Hu Y, Qin C, Zheng G et al (2016) Mesenchymal stem cell-educated macrophages ameliorate LPS-induced systemic response. Mediators Inflamm. https://doi.org/10.1155/2016/3735452

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yin Y, Wu RX, He XT et al (2017) Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture. Stem Cell Res Ther. https://doi.org/10.1186/s13287-017-0608-0

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the Ministry of Higher Education, Egypt and a Grant-in-Aid from the Ministry of Education, Science, Sports, Culture and Technology, Japan.

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Correspondence to Marwa El-Sayed.

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All experiments were approved by the Institutional Animal Care and Use Committee of Nagasaki University and performed in accordance with the institutional and national guidelines.

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El-Sayed, M., El-Feky, M.A., El-Amir, M.I. et al. Immunomodulatory effect of mesenchymal stem cells: Cell origin and cell quality variations. Mol Biol Rep 46, 1157–1165 (2019). https://doi.org/10.1007/s11033-018-04582-w

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