In vivo transfer of intracellular labels from locally implanted bone marrow stromal cells to resident tissue macrophages.
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.
Pawelczyk
Edyta
E
Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America. pawelczyke@cc.nih.gov
Jordan
Elaine K
EK
Balakumaran
Arun
A
Chaudhry
Aneeka
A
Gormley
Nicole
N
Smith
Melissa
M
Lewis
Bobbi K
BK
Childs
Richard
R
Robey
Pamela G
PG
Frank
Joseph A
JA
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*
D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine
Stem Cells. 2006 Aug;24(8):1968-75
16627684
J Neurosci. 2004 May 12;24(19):4585-95
15140930
Stem Cells. 2006 Mar;24(3):671-8
16179427
J Neurotrauma. 2007 Apr;24(4):625-37
17439346
Life Sci. 2006 Aug 1;79(10):999-1006
16828117
Blood. 2004 Aug 15;104(4):1217-23
15100158
Magn Reson Med. 2006 Jan;55(1):203-9
16315206
Cytotherapy. 2004;6(6):621-5
15773025
Stem Cells. 2006 Apr;24(4):1121-7
16373692
Cell Transplant. 2001 Jan-Feb;10(1):31-40
11294470
Cell Transplant. 2004;13(7-8):749-54
15690976
Circulation. 2007 Sep 11;116(11 Suppl):I38-45
17846324
Diabetes. 2006 Sep;55(9):2419-28
16936189
Methods Enzymol. 2006;419:117-48
17141054
Tissue Eng Part A. 2008 Jul;14(7):1149-60
18433314
Curr Protein Pept Sci. 2008 Aug;9(4):338-69
18691124
Gene Ther. 2008 May;15(10):730-8
18401438
Hum Gene Ther. 2004 Apr;15(4):351-60
15053860
Exp Neurol. 2006 Sep;201(1):49-59
16764862
Science. 1982 Oct 29;218(4571):474-5
7123245
Stem Cells. 2007 Nov;25(11):2936-44
17690182
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10211-6
17553967
Lab Invest. 2002 Jun;82(6):747-56
12065685
Stem Cells. 2006 Nov;24(11):2483-92
16873764
J Immunol. 2008 Feb 15;180(4):2581-7
18250469
Circulation. 2008 Mar 25;117(12):1555-62
18332264
Blood. 2005 Jan 1;105(1):420-5
15331444
Mol Ther. 2009 Jan;17(1):183-90
18985030
Eur Heart J. 2006 Jul;27(13):1620-6
16751204
PLoS One. 2008 Apr 02;3(4):e1886
18382669
Circ Res. 2003 Jul 25;93(2):114-23
12805240
Regen Med. 2007 Jan;2(1):51-62
17465775
Stem Cells. 2008 May;26(5):1366-75
18276802
Cancer Cell. 2005 Jan;7(1):101-11
15652753
Nat Clin Pract Cardiovasc Med. 2006 Oct;3(10):554-62
16990841
Nature. 1965 Aug 28;207(5000):953-6
5886931
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9
16061805
Invest Radiol. 2006 Mar;41(3):313-24
16481915
Neurosurgery. 2005 Oct;57(4):785-96; discussion 785-96
16239893
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10711-6
10485891
Science. 1985 Sep 20;229(4719):1268-71
4035355
Regen Med. 2008 Jul;3(4):531-46
18588475
J Neurosci Res. 2008 Mar;86(4):873-82
17975825
Blood. 2004 Jun 15;103(12):4619-21
15001472
Nat Med. 1999 Dec;5(12):1410-2
10581084
Nat Rev Immunol. 2008 Sep;8(9):726-36
19172693
Gene Ther. 2008 Nov;15(21):1446-53
18596829