Embryonic endothelial progenitor cells expressing a broad range of proangiogenic and remodeling factors enhance vascularization and tissue recovery in acute and chronic ischemia.
Clonal embryonic endothelial progenitor cells (eEPCs) isolated from embryonic day 7.5 mice home specifically to hypoxic areas in mouse tumor metastases but spare normal organs and do not form carcinomas. Based on these results, we assessed the potential of eEPCs to enhance vascularization and limit organ dysfunction after ischemia in syngenic and xenotypic organisms. The angiogenic potential of eEPCs was evaluated in chronic ischemic rabbit hindlimbs after regional application by retroinfusion. eEPC treatment improved limb perfusion, paralleled by an increase in capillary density and collateral blood vessel number. Systemic eEPC infusion into mice after ischemic cardiac insult increased postischemic heart output measured by a marked improvement in left ventricle developed pressure and both systolic and diastolic functions. In vitro, eEPCs strongly induced vascular outgrowths from aortic rings. To address the molecular basis of this intrinsic angiogenic potential, we investigated the eEPC transcriptome. Genome-wide Affymetrix GeneChip analysis revealed that the eEPCs express a wealth of secreted factors known to induce angiogenesis, tissue remodeling, and organogenesis that may contribute to the eEPC-mediated beneficial effects. Our findings show that eEPCs induce blood vessel growth and cardioprotection in severe ischemic conditions providing a readily available source to study the mechanisms of neovascularization and tissue recovery.
Kupatt
Christian
C
GSF-Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Munich, Germany.
Horstkotte
Jan
J
Vlastos
Georgios A
GA
Pfosser
Achim
A
Lebherz
Corinna
C
Semisch
Matthias
M
Thalgott
Mark
M
Büttner
Kerstin
K
Browarzyk
Christian
C
Mages
Jörg
J
Hoffmann
Reinhard
R
Deten
Alexander
A
Lamparter
Mathias
M
Müller
Fabian
F
Beck
Heike
H
Büning
Hildegard
H
Boekstegers
Peter
P
Hatzopoulos
Antonis K
AK
D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D006614:Hindlimb / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D018919:Neovascularization, Physiologic; D011817:Rabbits; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*