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Front Bioeng Biotechnol. 2019 Jun 12;7:142. doi: 10.3389/fbioe.2019.00142. eCollection 2019.

Pediatric Mesenchymal Stem Cells Exhibit Immunomodulatory Properties Toward Allogeneic T and B Cells Under Inflammatory Conditions.

Frontiers in bioengineering and biotechnology

Virginia Palomares Cabeza, Martin Johannes Hoogduijn, Rens Kraaijeveld, Marcella Franquesa, Janneke Witte-Bouma, Eppo B Wolvius, Eric Farrell, Pieter A J Brama

Affiliations

  1. Department of Oral and Maxillofacial Surgery, Erasmus University Medical Center, Rotterdam, Netherlands.
  2. Nephrology and Transplantation, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
  3. School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
  4. REMAR Group and Nephrology Service, Germans Trias i Pujol Health Science Institute and University Hospital, Badalona, Spain.

PMID: 31245368 PMCID: PMC6581756 DOI: 10.3389/fbioe.2019.00142

Abstract

Mesenchymal stem cells from pediatric patients (pMSCs) are an attractive cell source in regenerative medicine, due to their higher proliferation rates and better differentiation abilities compared to adult MSCs (aMSCs). We have previously characterized the immunomodulatory abilities of pMSCs on T cells under co-culture. It has also been reported that aMSCs can inhibit B cell proliferation and maturation under inflammatory conditions. In this study, we therefore aimed to clarify the immunomodulatory effect of pMSCs toward T and B cells in an inflammatory microenvironment. Bone marrow derived pMSCs were primed to simulate inflammatory conditions by exposure with 50 ng/mL of IFN-γ for 3 days. To analyze the interaction between pMSCs and T cells, CD3/CD28 stimulated peripheral blood mononuclear cells (PBMCs) were co-cultured with primed or unprimed pMSCs. To investigate B cell responses, quiescent B cells obtained from spleens by CD43 negative selection were stimulated with anti-IgM, anti-CD40, IL-2, and co-cultured with either IFN-γ primed or unprimed pMSC. pMSC phenotype, B and T cell proliferation, and B cell functionality were analyzed. Gene expression of indoleamine 2,3-dioxygenease (IDO), as well as the expression of HLA-ABC, HLA-DR and the co-stimulatory molecules CD80 and CD86 was upregulated on pMSCs upon IFN-γ priming. IFN-γ did not alter the immunomodulatory abilities of pMSCs upon CD4

Keywords: B cell; T cell; allogeneic; immunomodulation; inflammatory microenvironment; mesenchymal stem cell

References

  1. Exp Hematol. 2002 Jan;30(1):42-8 - PubMed
  2. J Biomed Sci. 2003 Mar-Apr;10(2):228-41 - PubMed
  3. Exp Hematol. 2003 Oct;31(10):890-6 - PubMed
  4. Blood. 2004 Jun 15;103(12):4619-21 - PubMed
  5. Stem Cells. 2006 Feb;24(2):386-98 - PubMed
  6. Blood. 2006 Jan 1;107(1):367-72 - PubMed
  7. Ageing Res Rev. 2006 Feb;5(1):91-116 - PubMed
  8. Am J Transplant. 2006 May;6(5 Pt 1):876-83 - PubMed
  9. Ann Neurol. 2007 Mar;61(3):219-27 - PubMed
  10. Clin Exp Immunol. 2007 Aug;149(2):353-63 - PubMed
  11. Stem Cells. 2007 Nov;25(11):2739-49 - PubMed
  12. Cell Stem Cell. 2008 Apr 10;2(4):313-9 - PubMed
  13. Gastroenterology. 2009 Mar;136(3):978-89 - PubMed
  14. Immunol Cell Biol. 2010 Nov-Dec;88(8):795-806 - PubMed
  15. BMC Musculoskelet Disord. 2011 Jan 31;12:31 - PubMed
  16. Stem Cells Dev. 2011 Dec;20(12):2115-26 - PubMed
  17. J Immunol. 2012 Jul 1;189(1):222-33 - PubMed
  18. PLoS One. 2012;7(9):e45185 - PubMed
  19. Nat Rev Rheumatol. 2013 Oct;9(10):584-94 - PubMed
  20. Stem Cells Dev. 2014 Apr 1;23(7):755-66 - PubMed
  21. Cell Death Differ. 2014 Mar;21(3):388-96 - PubMed
  22. J Immunol. 2014 Feb 15;192(4):1491-501 - PubMed
  23. Cytotherapy. 2014 Feb;16(2):191-202 - PubMed
  24. Eur Cell Mater. 2014 Feb 19;27:137-48; discussion 148 - PubMed
  25. Transpl Immunol. 2014 May;30(4):122-7 - PubMed
  26. Arthritis Rheumatol. 2014 Dec;66(12):3413-23 - PubMed
  27. Stem Cells. 2015 Mar;33(3):880-91 - PubMed
  28. Hepatol Int. 2014 Apr;8(2):179-84 - PubMed
  29. Immunobiology. 2016 Feb;221(2):129-36 - PubMed
  30. Biol Res. 2015 Nov 03;48:62 - PubMed
  31. Cell Death Dis. 2016 Jan 21;7:e2062 - PubMed
  32. Stem Cells Int. 2016;2016:1461648 - PubMed
  33. J Clin Invest. 2017 Jun 30;127(7):2473-2481 - PubMed
  34. Front Immunol. 2017 Aug 28;8:1042 - PubMed
  35. Transfus Apher Sci. 2017 Aug;56(4):498-505 - PubMed
  36. Cell Transplant. 2017 Sep;26(9):1520-1529 - PubMed
  37. Tissue Eng Part C Methods. 2018 Jun;24(6):313-321 - PubMed
  38. J Immunol Regen Med. 2018 Mar;1:45-56 - PubMed
  39. Stem Cells Dev. 2019 Jan 15;28(2):114-119 - PubMed

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