Novel Cell-Free Strategy for Therapeutic Angiogenesis In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation 英文参考文献.docVIP

Novel Cell-Free Strategy for Therapeutic Angiogenesis In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation 英文参考文献.doc

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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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