title: Autologous umbilical cord blood mononuclear cell transplantation preserves right ventricular function in a novel model of chronic right ventricular volume overload.
abstract: We aimed to evaluate the feasibility and efficacy of autologous umbilical cord blood mononuclear cell (UCMNC) transplantation on right ventricular (RV) function in a novel model of chronic RV volume overload. Four-month-old sheep (n = 20) were randomized into cell (n = 10) and control groups (n = 10). After assessment of baseline RV function by the conductance catheter method, a transannular patch (TAP) was sutured to the right ventricular outflow tract (RVOT). Following infundibulotomy the ring of the pulmonary valve was transected without cardiopulmonary bypass. UCMNC implantation (8.22 +/- 6.28 x 10(7)) in the cell group and medium injection in the control group were performed into the RV myocardium around the TAP. UCMNCs were cultured for 2 weeks after fluorescence-activated cell sorting (FACS) analysis for CD34 antigen. Transthoracic echocardiography (TTE) and computed tomography were performed after 6 weeks and 3 months, respectively. RV function was assessed 3 months postoperatively before the hearts were excised for immunohistological examinations. FACS analysis revealed 1.2 +/- 0.22% CD34(+) cells within the isolated UCMNCs from which AcLDL(+) endothelial cells were cultured in vitro. All animals survived surgery. TTE revealed grade II-III pulmonary regurgitation in both groups. Pressure-volume loops under dobutamine stress showed significantly improved RV diastolic function in the cell group (dP/dt(min): p = 0.043; E(ed): p = 0.009). CD31 staining indicated a significantly enhanced number of microvessels in the region of UCMNC implantation in the cell group (p < 0.001). No adverse tissue changes were observed. TAP augmentation and pulmonary annulus distortion without cardiopulmonary bypass constitutes a valid large animal model mimicking the surgical repair of tetralogy of Fallot. Our results indicate that the chronically volume-overloaded RV profits from autologous UCMNC implantation by enhanced diastolic properties with a probable underlying mechanism of increased angiogenesis.
authors.affiliation: Department of Cardiac Surgery, Medical Faculty, University of Rostock, Rostock, Germany. can.yerebakan@med.uni-rostock.de
authors.forename: Can
authors.initials: C
authors.lastname: Yerebakan
authors.forename: Eugen
authors.initials: E
authors.lastname: Sandica
authors.forename: Stephanie
authors.initials: S
authors.lastname: Prietz
authors.forename: Christian
authors.initials: C
authors.lastname: Klopsch
authors.forename: Murat
authors.initials: M
authors.lastname: Ugurlucan
authors.forename: Alexander
authors.initials: A
authors.lastname: Kaminski
authors.forename: Sefer
authors.initials: S
authors.lastname: Abdija
authors.forename: Björn
authors.initials: B
authors.lastname: Lorenzen
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.forename: Björn
authors.initials: B
authors.lastname: Nitzsche
authors.forename: Dietmar
authors.initials: D
authors.lastname: Egger
authors.forename: Malte
authors.initials: M
authors.lastname: Barten
authors.forename: Dario
authors.initials: D
authors.lastname: Furlani
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
authors.forename: Andreas
authors.initials: A
authors.lastname: Liebold
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
mesh_terms: D000818:Animals; D006348:Cardiac Surgical Procedures; D002306:Cardiac Volume / Q000502:physiology; D002478:Cells, Cultured; D002908:Chronic Disease; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D004452:Echocardiography; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology* / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D011183:Postoperative Complications / Q000000981:diagnostic imaging; D011897:Random Allocation; D012756:Sheep; D014182:Transplantation, Autologous / Q000379:methods; D018497:Ventricular Dysfunction, Right / Q000517:prevention & control*; D016278:Ventricular Function, Right / Q000502:physiology*; D014694:Ventricular Outflow Obstruction / Q000503:physiopathology / Q000628:therapy