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Biores Open Access. 2015 Jan 01;4(1):75-88. doi: 10.1089/biores.2014.0029. eCollection 2015.

CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network Formation of Blood-Derived Endothelial Outgrowth Cells.

BioResearch open access

Erica B Peters, Nicolas Christoforou, Erika Moore, Jennifer L West, George A Truskey

Affiliations

  1. Department of Biomedical Engineering, Duke University , Durham, North Carolina.
  2. Department of Biomedical Engineering, Duke University , Durham, North Carolina. ; Department of Biomedical Engineering, Khalifa University , Abu Dhabi, United Arab Emirates .
  3. Department of Biomedical Engineering, Duke University , Durham, North Carolina. ; Department of Mechanical Engineering and Materials Science, Duke University , Durham, North Carolina. ; Department of Cell Biology, Duke University , Durham, North Carolina. ; Department of Chemistry, Duke University , Durham, North Carolina.

PMID: 26309784 PMCID: PMC4497669 DOI: 10.1089/biores.2014.0029

Abstract

Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) represent promising cell sources for angiogenic therapies. There are, however, conflicting reports regarding the ability of MSCs to support network formation of endothelial cells. The goal of this study was to assess the ability of human bone marrow-derived MSCs to support network formation of endothelial outgrowth cells (EOCs) derived from umbilical cord blood EPCs. We hypothesized that upon in vitro coculture, MSCs and EOCs promote a microenvironment conducive for EOC network formation without the addition of angiogenic growth supplements. EOC networks formed by coculture with MSCs underwent regression and cell loss by day 10 with a near 4-fold and 2-fold reduction in branch points and mean segment length, respectively, in comparison with networks formed by coculture vascular smooth muscle cell (SMC) cocultures. EOC network regression in MSC cocultures was not caused by lack of vascular endothelial growth factor (VEGF)-A or changes in TGF-β1 or Ang-2 supernatant concentrations in comparison with SMC cocultures. Removal of CD45+ cells from MSCs improved EOC network formation through a 2-fold increase in total segment length and number of branch points in comparison to unsorted MSCs by day 6. These improvements, however, were not sustained by day 10. CD45 expression in MSC cocultures correlated with EOC network regression with a 5-fold increase between day 6 and day 10 of culture. The addition of supplemental growth factors VEGF, fibroblastic growth factor-2, EGF, hydrocortisone, insulin growth factor-1, ascorbic acid, and heparin to MSC cocultures promoted stable EOC network formation over 2 weeks in vitro, without affecting CD45 expression, as evidenced by a lack of significant differences in total segment length (p=0.96). These findings demonstrate the ability of MSCs to support EOC network formation correlates with removal of CD45+ cells and improves upon the addition of soluble growth factors.

Keywords: angiogenesis; endothelial progenitor cells; mesenchymal stem cells; microvessel tissue engineering; umbilical cord blood; vasculogenesis

References

  1. Biochem Biophys Res Commun. 2010 Sep 17;400(2):284-91 - PubMed
  2. Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1584-95 - PubMed
  3. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5026-30 - PubMed
  4. Adv Drug Deliv Rev. 2011 Apr 30;63(4-5):291-9 - PubMed
  5. J Invest Dermatol. 1990 Dec;95(6 Suppl):85S-89S - PubMed
  6. Biochem Biophys Res Commun. 1988 Aug 30;155(1):429-35 - PubMed
  7. Stem Cells Dev. 2014 Feb 15;23(4):319-32 - PubMed
  8. Exp Cell Res. 1985 Dec;161(2):297-306 - PubMed
  9. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1457-64 - PubMed
  10. J Immunol. 2004 Jun 15;172(12):7565-73 - PubMed
  11. Methods. 2003 Dec;31(4):265-73 - PubMed
  12. Adv Funct Mater. 2012 May 23;22(10):2027-2039 - PubMed
  13. J Clin Invest. 2007 May;117(5):1155-66 - PubMed
  14. Stem Cells. 2013 Jan;31(1):146-55 - PubMed
  15. Cancer Res. 2014 Mar 1;74(5):1287-93 - PubMed
  16. J Biomed Mater Res A. 2012 Mar;100(3):561-70 - PubMed
  17. J Cell Biol. 1987 Mar;104(3):689-96 - PubMed
  18. Expert Opin Biol Ther. 2010 Oct;10(10):1441-51 - PubMed
  19. Cell Stem Cell. 2008 Sep 11;3(3):229-30 - PubMed
  20. Lab Invest. 2005 Oct;85(10):1189-98 - PubMed
  21. Circulation. 2012 Jan 3;125(1):87-99 - PubMed
  22. Cell Tissue Res. 2003 Oct;314(1):61-8 - PubMed
  23. J Leukoc Biol. 1994 Mar;55(3):410-22 - PubMed
  24. Blood. 2009 Apr 30;113(18):4197-205 - PubMed
  25. Cancer Res. 2007 Apr 15;67(8):3835-44 - PubMed
  26. PLoS One. 2013;8(3):e58897 - PubMed
  27. Cytotherapy. 2006;8(4):315-7 - PubMed
  28. Cells. 2013 Sep 16;2(3):621-34 - PubMed
  29. Stem Cells Dev. 2013 Jan 1;22(1):148-57 - PubMed
  30. Mol Cell. 2010 Mar 12;37(5):643-55 - PubMed
  31. Ann N Y Acad Sci. 2012 Aug;1266:94-106 - PubMed
  32. Stem Cells. 2004;22(3):377-84 - PubMed
  33. PLoS One. 2009 Jun 04;4(6):e5798 - PubMed
  34. J Cell Physiol. 2012 Nov;227(11):3546-55 - PubMed
  35. Stem Cells Dev. 2013 Feb 15;22(4):643-53 - PubMed
  36. Biomed Res Int. 2014;2014:395781 - PubMed
  37. Nat Commun. 2013;4:1886 - PubMed
  38. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6624-8 - PubMed
  39. FASEB J. 2001 Feb;15(2):447-57 - PubMed
  40. Tissue Eng Part A. 2013 Mar;19(5-6):697-706 - PubMed
  41. Nat Immunol. 2013 Oct;14(10):986-95 - PubMed
  42. Stem Cell Rev. 2011 Sep;7(3):560-8 - PubMed
  43. Microvasc Res. 2010 Jul;80(1):166-73 - PubMed
  44. Circ Res. 2008 Jul 18;103(2):194-202 - PubMed
  45. Tissue Eng Part A. 2012 Dec;18(23-24):2395-405 - PubMed
  46. Nat Rev Mol Cell Biol. 2007 Jun;8(6):464-78 - PubMed
  47. Endothelium. 2006 Mar-Apr;13(2):63-9 - PubMed
  48. Lymphology. 2010 Jun;43(2):59-72 - PubMed
  49. Angiogenesis. 2012 Jun;15(2):253-64 - PubMed
  50. Br Med Bull. 2013;108:25-53 - PubMed
  51. PLoS One. 2012;7(10 ):e46842 - PubMed
  52. Blood. 2004 Nov 1;104(9):2752-60 - PubMed
  53. Blood. 2011 Dec 15;118(25):6718-21 - PubMed
  54. Adv Mater. 2012 May 2;24(17):2344-8 - PubMed
  55. Regen Med. 2008 Nov;3(6):877-92 - PubMed
  56. Circ Res. 2005 Nov 25;97(11):1093-107 - PubMed

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