Use of recombinant adeno-associated viral vectors as a tool for labeling bone marrow cells.
We have tested the feasibility of using recombinant adeno-associated virus (rAAV) vectors as a tool for labeling bone marrow (BM) cells in vivo. We infected BM cells of donor FVB mice with rAAV vectors containing the lacZ gene for 2 h. We then injected the rAAV-infected cells to lethally irradiated-recipient FVB mice. Peripheral blood (PB), BM and spleen harvested at 4 weeks after BM transplant (BMT) demonstrated stable engraftment in beta-galactosidase (beta-gal) expression. In contrast, Dil-labeling displayed only a faint signal 4 weeks after BMT. To analyze the kinetics of BM cells, we injected vascular endothelial growth factor (VEGF), which promotes mobilization of BM cells. Administration of VEGF protein significantly increased the rAAV-mediated beta-gal expression in PB and BM of recipient mice. Moreover, when myocardial infarction was induced in BMT mice, the ischemic area exhibited significant beta-gal staining in rAAV-labeled BMT group. rAAV vectors programmed stable transduction in BM cells in vivo through rapid infection. rAAV appears to represent a useful vector for labeling BM cells ex vivo prior to BMT for analysis of cardiovascular therapeutic purposes.
Iwakura
Atsushi
A
Cardiovascular Research, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge Street, Boston, MA 02135, USA.
Dean
Jarrod
J
Hamada
Hiromichi
H
Eaton
Elizabeth
E
Qin
Giangjin
G
Losordo
Douglas W
DW
Aikawa
Ryuichi
R
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000187:drug effects / Q000821:virology*; D016026:Bone Marrow Transplantation; D004279:DNA, Viral / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors; D066298:In Vitro Techniques; D007763:Lac Operon / Q000187:drug effects; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D004279:DNA, Viral; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A