Novel Cell-Free Strategy for Therapeutic Angiogenesis In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation 英文参考文献.docVIP
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Novel Cell-Free Strategy for Therapeutic Angiogenesis In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation 英文参考文献
NovelCell-FreeStrategyforTherapeuticAngiogenesis:In
VitroGeneratedConditionedMediumCanReplace
ProgenitorCellTransplantation
StefanoDiSanto.,ZijiangYang.,MoritzWylervonBallmoos,JanVoelzmann,NicolasDiehm,Iris
Baumgartner,ChristophKalka*
DepartmentofVascularMedicine,SwissCardiovascularCenter,Inselspital,BernUniversityHospital,UniversityofBern,Bern,Switzerland
Abstract
Background:Currentevidencesuggeststhatendothelialprogenitorcells(EPC)contributetoischemictissuerepairbyboth
secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free
administrationofparacrinefactorssecretedbyculturedEPCmayachieveanangiogeniceffectequivalenttocelltherapy.
Methodology/Principal Findings: EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC
subjected to 72hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and
promotedangiogenesisinarataorticringassay.ThetherapeuticpotentialofEPC-CMascomparedtoEPCtransplantation
was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both
significantlyincreasedhindlimbbloodflowassessedbylaserDoppler(81.262.9%and83.763.0%vs.53.562.4%ofnormal,
P,0.01) andimproved muscle performance. Asignificantly increased capillary density (1.6260.03 and1.6860.05/muscle
fiber, P,0.05), enhanced vascular maturation (8.660.3 and 8.160.4/HPF, P,0.05) and muscle viability corroborated the
findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the
+
mobilizationofbonemarrow(BM)-derivedEPCcomparedtocontrol(678.7644.1vs.340.0629.1CD34 /CD452cells/16105
+
mononuclearcells,P,0.05)andtheirrecruitmenttotheischemicmuscles(5.960.7vs.2.660.4CD34 cells/HPF,P,0.001)3
daysafterthelastinjection.
Conclusions/Significance: Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue
revascularization and functional reco
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