CD34 expression on murine marrow-derived mesenchymal stromal cells: impact on neovascularization.
OBJECTIVE
CD34 is a sialomucin often expressed by cells with hemangiopoietic potential and widely serves as a surrogate marker of stem cell potential. Mesenchymal stromal cells (MSCs) also express CD34, although the functional significance of its expression remains undefined. In this study, we determined whether CD34(pos) MSCs are functionally distinct from CD34(null) MSCs.


METHODS
MSCs derived from C57Bl/6 mice were transduced to express the green fluorescent protein (GFP) from which pure CD34(pos) MSC and CD34(null) MSC clones were selected. In vitro, clones were examined by microarray analysis, while in vivo subcutaneous implantation of matrix-embedded MSCs was used to assess cell survival, differentiation, and neovascularization.


RESULTS
The flow cytometric phenotype of CD34(pos) and CD34(null) MSCs were similar, as was gene expression of vascular endothelial growth factors (VEGFs) A and B. However, CD34(pos) MSCs upregulated a number of supplementary angiogenesis-associated genes and showed a greater expression of gene associated with vascular differentiation. At 15 days postimplantation, cell survival between CD34(pos) and CD34(null) MSCs was similar, however, CD34(pos) MSCs evoked a significantly greater host-derived response (4.2 +/- 0.7 vs 1.9 +/- 0.5 x 10(6) cells; p < 0.05). GFP-expressing CD34(pos) MSC implants acquired significantly more CD31 expression compared to CD34(null) MSC cells (10.7% +/- 8.4% vs 3.1% +/- 0.6%; p < 0.05), as well as a significantly greater host-derived endothelial cell influx (CD31(+)/CD45(-)).


CONCLUSIONS
CD34 expression by MSCs correlates with enhanced vasculogenic and angiogenic potential in vivo.
Copland
Ian
I
Lady Davis Institute for Research, Jewish General Hospital, Montreal, Canada.
Sharma
Kapil
K
Lejeune
Laurence
L
Eliopoulos
Nicoletta
N
Stewart
Duncan
D
Liu
Peter
P
Lachapelle
Kevin
K
Galipeau
Jacques
J
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis*; D015415:Biomarkers; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D016130:Immunophenotyping; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D042787:Receptor, TIE-2 / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry / Q000166:cytology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D051941:fms-Like Tyrosine Kinase 3 / Q000032:analysis
D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D049452:Green Fluorescent Proteins; C497971:Flt3 protein, mouse; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2; D051941:fms-Like Tyrosine Kinase 3