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In vivo cardiac pacem.ker function of differentiated hum.n m.senchym.l stem.cells from.adipose tissue transplanted into porcine hearts

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

作者： Fabrice F Darche Rasm.s Rivinius Ann-Kathrin rahm Eva Köllensperger Uwe Leim.r Günter Germ.nn m.riam.Reiss m.chael Koenen Hugo A Katus Dierk Thom.s Patrick A Schweizer Departm.nt of Cardiology Medical University Hospital HeidelbergHeidelberg D-69120Germany DZHK(Germ.n Centre for Cardiovascular Research) Partner Site Heidelberg/MannheimUniversity of HeidelbergHeidelberg D-69120Germany HCR(Heidelberg Center for Heart Rhythm.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.senchym.l stem.cells(m.C)m.dified by gene transfer to express cardiac pacem.ker channels such as HCn2 or HCn4 were shown to elicit pacem.ker function after intracardiac transplantation in experim.ntal anim.l *** m.C derived from.adipose tissue(ham.C)differentiate into cells with pacem.ker properties in vitro,but little is known about their behavior after intracardiac *** To investigate whether ham.C elicit biological pacem.ker function in vivo after transplantation into pig *** ham.C under native conditions(nham.C)or after pre-conditioning by m.dium.differentiation(dham.C)(n=6 pigs each,5×106 cells/anim.l)were injected into the porcine left ventricular free *** receiving PBS injection served as controls(n=6).Four weeks later,total atrioventricular(AV)-block was induced by radiofrequency catheter ablation,and electronic pacem.ker devices were im.lanted for backup stim.lation and heart rate *** rate and rhythm.of pigs were evaluated during a follow-up of 15 d post ablation by 12-lead-ECG with heart rate assessm.nt,24-h continuous rate m.nitoring recorded by electronic pacem.ker,assessm.nt of escape recovery tim.,and pharm.cological challenge to address catecholam.nergic rate ***,hearts were analyzed by histological and im.unohistochem.cal *** In vivo transplantation of dham.C into the left ventricular free wall of pigs elicited spontaneous and regular rhythm. that were pace-m.pped to ventricular injection sites(m.an heart rate 72.2±3.6 bpm.n=6)after experim.ntal total AV *** rhythm. were stably detected over a 15-d period and were sensitive to catecholam.nergic stim.lation(m.an m.xim.m.heart rate 131.0±6.2 bpm.n=6;Pnham.C or PBS presented significantly lower ventricular rates(m.an heart rates 47.2±2.5 bpm.and 37.4±3.2 bpm.respectively;n=6 each;Pnd exhibited little sensitivity towards catecholam.nergic stim.latio

关键词： Biological cardiac pacem.ker m.senchym.l stem.cells Differentiation Anim.l m.del Cell transplantation Stem.cell therapy

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