Global transcriptome analysis of human bone marrow stromal cells (BMSC) reveals proliferative, mobile and interactive cells that produce abundant extracellular matrix proteins, some of which may affect BMSC potency.
OBJECTIVE
Bone marrow stromal cells (BMSC) are being used for immune modulatory, anti-inflammatory and tissue engineering applications, but the properties responsible for these effects are not completely understood. Human BMSC were characterized to identify factors that might be responsible for their clinical effects and biomarkers for assessing their quality.


METHODS
Early passage BMSC prepared from marrow aspirates of seven healthy subjects were compared with three human embryonic stem cell (hESC) samples, CD34(+) cells from three healthy subjects and three fibroblast cell lines. The cells were analyzed with oligonucleotide expression microarrays with more than 35 000 probes.


RESULTS
BMSC gene expression signatures of BMSC differed from those of hematopoietic stem cells (HSC), hESC and fibroblasts. Genes upregulated in BMSC were involved with cell movement, cell-to-cell signaling and interaction and proliferation. The upregulated genes most probably belonged to pathways for integrin signaling, integrin-linked kinase (ILK) signaling, NF-E2-related factor-2 (NFR2)-mediated oxidative stress response, regulation of actin-based motility by Rho, actin cytoskeletal signaling, caveolar-mediated endocytosis, clathrin-mediated endocytosis and Wingless-type MMTV integration site (Wnt/β catenin signaling. Among the most highly upregulated genes were structural extracellular matrix (ECM) proteins (α5 and β5 integrin chains, fibronectin and collagen type IIIα1 and Vα1) and functional EMC proteins [connective tissue growth factor (CTGF), transforming growth factor beta-induced protein (TGFBI) and A disintegrin and metalloproteinase (ADAM12)].


CONCLUSIONS
Global analysis of human BMSC suggests that they are mobile, metabolically active, proliferative and interactive cells that make use of integrins and integrin signaling. They produce abundant ECM proteins that may contribute to their clinical immune modulatory and anti-inflammatory effects.
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1288, USA.
Jiaqiang
J
Ren
Ping
P
Jin
Marianna
M
Sabatino
Arun
A
Balakumaran
Ji
J
Feng
Sergei A
SA
Kuznetsov
Harvey G
HG
Klein
Pamela G
PG
Robey
David F
DF
Stroncek
D051722:ADAM Proteins / Q000235:genetics; D000072199:ADAM12 Protein; D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D000099222:betaIG-H3 Protein; D000099200:Scaffold Protein ILK
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D055513:Connective Tissue Growth Factor; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D017346:Protein Serine-Threonine Kinases; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; D000099200:Scaffold Protein ILK; C526317:CCN2 protein, human; C000606480:ADAM12 protein, human
Bone Marrow Transplant. 2002 Aug;30(4):215-22
12203137
J Intern Med. 2007 Nov;262(5):509-25
17949362
Stem Cells. 2006 Sep;24(9):2140-9
16763200
Annu Rev Biochem. 2009;78:857-902
19317650
J Cell Mol Med. 2009 Jun;13(6):1175-84
18681910
Int J Biochem Cell Biol. 2008;40(9):1685-702
18342566
Stroke. 2001 Apr;32(4):1005-11
11283404
Stem Cells. 2007 Aug;25(8):1966-74
17510214
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
9843981
Biochem Biophys Res Commun. 2005 Dec 30;338(4):1759-65
16288716
Cancer Res. 2002 Jul 1;62(13):3581-6
12097256
Mult Scler. 2010 Apr;16(4):503-10
20086020
Am J Pathol. 2006 Feb;168(2):542-50
16436668
Stem Cells Dev. 2007 Feb;16(1):53-73
17348805
Expert Opin Biol Ther. 2009 Dec;9(12):1487-97
19821796
Biochem Biophys Res Commun. 2009 Dec 18;390(3):902-7
19852944
Liver Transpl. 2010 Feb;16(2):118-29
20104479
Expert Rev Clin Immunol. 2010 Mar;6(2):211-8
20402384
Vitam Horm. 2005;70:69-103
15727802
Matrix Biol. 2007 Jun;26(5):371-81
17306970
Tissue Eng Part A. 2008 Dec;14(12):1949-58
18800877
Circulation. 2006 Jan 17;113(2):238-45
16401770
Biol Blood Marrow Transplant. 2005 May;11(5):321-34
15846285
Neurosci Lett. 2009 Jun 12;456(3):120-3
19429146
Front Biosci (Landmark Ed). 2009 Jan 01;14:2307-34
19273203
Cancer Res. 2009 Jan 1;69(1):37-44
19117985
PLoS One. 2009 Aug 25;4(8):e6743
19707545
Breast Cancer Res Treat. 2008 Jul;110(1):39-49
17674196
Genome Biol. 2003;4(5):P3
12734009
Immunol Rev. 2005 Dec;208:126-40
16313345
Blood. 2007 Oct 1;110(7):2764-7
17638847
Lancet. 2008 May 10;371(9624):1579-86
18468541
Stem Cells. 2005 Apr;23(4):584-93
15790779
Biomaterials. 2008 Nov;29(31):4211-6
18687465
Stem Cells. 2007 Nov;25(11):2896-902
17901396
Neurosurgery. 2004 Nov;55(5):1185-93
15509325
Blood. 2008 Jul 15;112(2):295-307
18332228
Cytotherapy. 2008;10(8):771-4
19089685
Cytotherapy. 2009;11(4):377-91
19568970
Cell Stem Cell. 2008 Apr 10;2(4):313-9
18397751
Haematologica. 2008 Jan;93(1):e11-3
18166768
J Transl Med. 2009 Mar 23;7:20
19309508
Int J Mol Med. 2008 Mar;21(3):271-9
18288373
Ann Rheum Dis. 2010 Jan;69 Suppl 1:i86-88
19995753
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8932-7
12084934
Arch Immunol Ther Exp (Warsz). 2008 Sep-Oct;56(5):325-9
18836860
Biofactors. 2009 Mar-Apr;35(2):200-8
19449449
J Cell Biochem. 2006 Aug 1;98(5):1076-84
16619257