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In vivo cardiac pacem.ker function of differentiated h.m.n m.sench.m.l stem.cells from.adipose tissue transplanted into porcine h.arts

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World Journal of Stem.Cells 2020年第10期12卷 1133-1151页

作者： Fabrice F Darch. Rasm.s Rivinius Ann-Kath.in rahm Eva Köllensperger Uwe Leim.r Günter Germ.nn m.riam.Reiss m.ch.el Koenen h.go A Katus Dierk Th.m.s Patrick A Sch.eizer Departm.nt of Cardiology Medical University Hospital HeidelbergHeidelberg D-69120Germany DZh.(Germ.n Centre for Cardiovascular Research. Partner Site Heidelberg/MannheimUniversity of HeidelbergHeidelberg D-69120Germany h.R(h.idelberg Center for h.art Rh.th. Disorders) Department of CardiologyMedical University Hospital HeidelbergHeidelberg D-69120Germany Departm.nt of Plastic Surgery ETHIANUM Klinik HeidelbergHeidelberg D-69115Germany Departm.nt of m.lecular neurobiology Max-Planck-Institute for Medical ResearchHeidelberg D-69120Germany

BACKGROUnD m.sench.m.l stem.cells(m.C)m.dified by gene transfer to express cardiac pacem.ker ch.nnels such.as h.n2 or h.n4 were sh.wn to elicit pacem.ker function after intracardiac transplantation in experim.ntal anim.l *** m.C derived from.adipose tissue(h.m.C)differentiate into cells with.pacem.ker properties in vitro,but little is known about th.ir beh.vior after intracardiac *** To investigate wh.th.r h.m.C elicit biological pacem.ker function in vivo after transplantation into pig *** h.m.C under native conditions(nh.m.C)or after pre-conditioning by m.dium.differentiation(dh.m.C)(n=6 pigs each.5×106 cells/anim.l)were injected into th. porcine left ventricular free *** receiving PBS injection served as controls(n=6).Four weeks later,total atrioventricular(AV)-block was induced by radiofrequency cath.ter ablation,and electronic pacem.ker devices were im.lanted for backup stim.lation and h.art rate *** rate and rh.th. of pigs were evaluated during a follow-up of 15 d post ablation by 12-lead-ECG with.h.art rate assessm.nt,24-h.continuous rate m.nitoring recorded by electronic pacem.ker,assessm.nt of escape recovery tim.,and ph.rm.cological ch.llenge to address catech.lam.nergic rate ***,h.arts were analyzed by h.stological and im.unoh.stoch.m.cal *** In vivo transplantation of dh.m.C into th. left ventricular free wall of pigs elicited spontaneous and regular rh.th.s th.t were pace-m.pped to ventricular injection sites(m.an h.art rate 72.2±3.6 bpm.n=6)after experim.ntal total AV *** rh.th.s were stably detected over a 15-d period and were sensitive to catech.lam.nergic stim.lation(m.an m.xim.m.h.art rate 131.0±6.2 bpm.n=6;Ph.ch.received nh.m.C or PBS presented significantly lower ventricular rates(m.an h.art rates 47.2±2.5 bpm.and 37.4±3.2 bpm.respectively;n=6 each.Pnd exh.bited little sensitivity towards catech.lam.nergic stim.latio

关键词： Biological cardiac pacem.ker m.sench.m.l stem.cells Differentiation Anim.l m.del Cell transplantation Stem.cell th.rapy

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