Bone marrow-derived cells do not repair endothelium in a mouse model of chronic endothelial cell dysfunction.
OBJECTIVE
Bone marrow (BM)-derived endothelial progenitor cells (EPCs) in the circulation replace damaged vascular endothelium. We assessed the hypothesis that a BM transplant from healthy animals would restore normal arterial endothelium and prevent hypertension in young endothelial nitric oxide synthase-deficient (eNOS(-/-)) mice.


RESULTS
Radiation or busulfan-induced BM ablation in eNOS(-/-) mice on day 6, day 14, or day 28 was followed by a BM transplant consisting of enhanced green fluorescent protein positive (EGFP(+)) cells from C57BL/6J mice. Peripheral blood cell chimerism was always greater than 85% at 4 months after BM transplant. Molecular assays of heart, kidney, and liver revealed low-level chimerism in all treatment groups, consistent with residual circulating EGFP(+) blood cells. When aorta, coronary, renal, hepatic, and splenic arteries in BM-transplanted eNOS(-/-) mice were examined by confocal microscopy, there were no EGFP- or eNOS-positive endothelial cells detected in these vessels in any of the treatment groups. Likewise, telemetry did not detect any reduction in blood pressure. Thus, no differences were observed in our measurements using several different treatment protocols.


CONCLUSIONS
We found no evidence for BM-derived EPC renewal of endothelium in this eNOS-deficient mouse model of a chronic vascular disease or in wild-type mice during postnatal growth. Hence, renewal of chronic dysfunctional endothelium and endothelial homeostasis may be dependent on resident vascular progenitor cells.
Perry
Tashera E
TE
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Building 10-CRC, Room 6-3130, Bethesda, MD 20892, USA.
Song
Minjung
M
Despres
Daryl J
DJ
Kim
Soo Mi
SM
San
Hong
H
Yu
Zu-Xi
ZX
Raghavachari
Nalini
N
Schnermann
Jurgen
J
Cannon
Richard O
RO
Orlic
Donald
D
D000818:Animals; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D001835:Body Weight; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009206:Myocardium / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D033581:Stem Cell Transplantation; D013686:Telemetry; D013997:Time Factors; D018183:Transplantation Chimera
D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse