title: Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy.
abstract: Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.
authors.affiliation: Arizona Heart Institute, 2632 N. 20th Street, Phoenix, AZ 85006, USA. Ndib@azheart.com
authors.forename: Nabil
authors.initials: N
authors.lastname: Dib
authors.forename: Patrick
authors.initials: P
authors.lastname: McCarthy
authors.forename: Ann
authors.initials: A
authors.lastname: Campbell
authors.forename: Michael
authors.initials: M
authors.lastname: Yeager
authors.forename: Francis D
authors.initials: FD
authors.lastname: Pagani
authors.forename: Susan
authors.initials: S
authors.lastname: Wright
authors.forename: W Robb
authors.initials: WR
authors.lastname: MacLellan
authors.forename: Gregg
authors.initials: G
authors.lastname: Fonarow
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Eisen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Michler
authors.forename: Philip
authors.initials: P
authors.lastname: Binkley
authors.forename: Diane
authors.initials: D
authors.lastname: Buchele
authors.forename: Ronald
authors.initials: R
authors.lastname: Korn
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghazoul
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dinsmore
authors.forename: Shaun R
authors.initials: SR
authors.lastname: Opie
authors.forename: Edward
authors.initials: E
authors.lastname: Diethrich
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D004452:Echocardiography; D005240:Feasibility Studies; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D006353:Heart-Assist Devices; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000166:cytology; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D013318:Stroke Volume / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology