title: In vivo transfer of intracellular labels from locally implanted bone marrow stromal cells to resident tissue macrophages.
abstract: Intracellular labels such as dextran coated superparamagnetic iron oxide nanoparticles (SPION), bromodeoxyuridine (BrdU) or green fluorescent protein (GFP) are frequently used to study the fate of transplanted cells by in vivo magnetic resonance imaging or fluorescent microscopy. Bystander uptake of labeled cells by resident tissue macrophages (TM) can confound the interpretation of the presence of intracellular labels especially during direct implantation of cells, which can result in more than 70% cell death. In this study we determined the percentages of TM that took up SPION, BrdU or GFP from labeled bone marrow stromal cells (BMSCs) that were placed into areas of angiogenesis and inflammation in a mouse model known as Matrigel plaque perfusion assay. Cells recovered from digested plaques at various time points were analyzed by fluorescence microscopy and flow cytometry. The analysis of harvested plaques revealed 5% of BrdU(+), 5-10% of GFP(+) and 5-15% of dextran(+) macrophages. The transfer of the label was not dependent on cell dose or viability. Collectively, this study suggests that care should be taken to validate donor origin of cells using an independent marker by histology and to assess transplanted cells for TM markers prior to drawing conclusions about the in vivo behavior of transplanted cells.
authors.affiliation: Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America. pawelczyke@cc.nih.gov
authors.forename: Edyta
authors.initials: E
authors.lastname: Pawelczyk
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Jordan
authors.forename: Arun
authors.initials: A
authors.lastname: Balakumaran
authors.forename: Aneeka
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Nicole
authors.initials: N
authors.lastname: Gormley
authors.forename: Melissa
authors.initials: M
authors.lastname: Smith
authors.forename: Bobbi K
authors.initials: BK
authors.lastname: Lewis
authors.forename: Richard
authors.initials: R
authors.lastname: Childs
authors.forename: Pamela G
authors.initials: PG
authors.lastname: Robey
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Frank
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D019070:Cell Lineage; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008856:Microscopy, Fluorescence; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine
references.citation: Stem Cells. 2006 Aug;24(8):1968-75
references.pmid: 16627684
references.citation: J Neurosci. 2004 May 12;24(19):4585-95
references.pmid: 15140930
references.citation: Stem Cells. 2006 Mar;24(3):671-8
references.pmid: 16179427
references.citation: J Neurotrauma. 2007 Apr;24(4):625-37
references.pmid: 17439346
references.citation: Life Sci. 2006 Aug 1;79(10):999-1006
references.pmid: 16828117
references.citation: Blood. 2004 Aug 15;104(4):1217-23
references.pmid: 15100158
references.citation: Magn Reson Med. 2006 Jan;55(1):203-9
references.pmid: 16315206
references.citation: Cytotherapy. 2004;6(6):621-5
references.pmid: 15773025
references.citation: Stem Cells. 2006 Apr;24(4):1121-7
references.pmid: 16373692
references.citation: Cell Transplant. 2001 Jan-Feb;10(1):31-40
references.pmid: 11294470
references.citation: Cell Transplant. 2004;13(7-8):749-54
references.pmid: 15690976
references.citation: Circulation. 2007 Sep 11;116(11 Suppl):I38-45
references.pmid: 17846324
references.citation: Diabetes. 2006 Sep;55(9):2419-28
references.pmid: 16936189
references.citation: Methods Enzymol. 2006;419:117-48
references.pmid: 17141054
references.citation: Tissue Eng Part A. 2008 Jul;14(7):1149-60
references.pmid: 18433314
references.citation: Curr Protein Pept Sci. 2008 Aug;9(4):338-69
references.pmid: 18691124
references.citation: Gene Ther. 2008 May;15(10):730-8
references.pmid: 18401438
references.citation: Hum Gene Ther. 2004 Apr;15(4):351-60
references.pmid: 15053860
references.citation: Exp Neurol. 2006 Sep;201(1):49-59
references.pmid: 16764862
references.citation: Science. 1982 Oct 29;218(4571):474-5
references.pmid: 7123245
references.citation: Stem Cells. 2007 Nov;25(11):2936-44
references.pmid: 17690182
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10211-6
references.pmid: 17553967
references.citation: Lab Invest. 2002 Jun;82(6):747-56
references.pmid: 12065685
references.citation: Stem Cells. 2006 Nov;24(11):2483-92
references.pmid: 16873764
references.citation: J Immunol. 2008 Feb 15;180(4):2581-7
references.pmid: 18250469
references.citation: Circulation. 2008 Mar 25;117(12):1555-62
references.pmid: 18332264
references.citation: Blood. 2005 Jan 1;105(1):420-5
references.pmid: 15331444
references.citation: Mol Ther. 2009 Jan;17(1):183-90
references.pmid: 18985030
references.citation: Eur Heart J. 2006 Jul;27(13):1620-6
references.pmid: 16751204
references.citation: PLoS One. 2008 Apr 02;3(4):e1886
references.pmid: 18382669
references.citation: Circ Res. 2003 Jul 25;93(2):114-23
references.pmid: 12805240
references.citation: Regen Med. 2007 Jan;2(1):51-62
references.pmid: 17465775
references.citation: Stem Cells. 2008 May;26(5):1366-75
references.pmid: 18276802
references.citation: Cancer Cell. 2005 Jan;7(1):101-11
references.pmid: 15652753
references.citation: Nat Clin Pract Cardiovasc Med. 2006 Oct;3(10):554-62
references.pmid: 16990841
references.citation: Nature. 1965 Aug 28;207(5000):953-6
references.pmid: 5886931
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9
references.pmid: 16061805
references.citation: Invest Radiol. 2006 Mar;41(3):313-24
references.pmid: 16481915
references.citation: Neurosurgery. 2005 Oct;57(4):785-96; discussion 785-96
references.pmid: 16239893
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10711-6
references.pmid: 10485891
references.citation: Science. 1985 Sep 20;229(4719):1268-71
references.pmid: 4035355
references.citation: Regen Med. 2008 Jul;3(4):531-46
references.pmid: 18588475
references.citation: J Neurosci Res. 2008 Mar;86(4):873-82
references.pmid: 17975825
references.citation: Blood. 2004 Jun 15;103(12):4619-21
references.pmid: 15001472
references.citation: Nat Med. 1999 Dec;5(12):1410-2
references.pmid: 10581084
references.citation: Nat Rev Immunol. 2008 Sep;8(9):726-36
references.pmid: 19172693
references.citation: Gene Ther. 2008 Nov;15(21):1446-53
references.pmid: 18596829