Authors: Yerebakan, Can; Sandica, Eugen; Prietz, Stephanie; Klopsch, Christian; Ugurlucan, Murat; Kaminski, Alexander; Abdija, Sefer; Lorenzen, Björn; Boltze, Johannes; Nitzsche, Björn; Egger, Dietmar; Barten, Malte; Furlani, Dario; Ma, Nan; Vollmar, Brigitte; Liebold, Andreas; Steinhoff, Gustav

Source: Cell Transplantation, Volume 18, Number 8, 2009 , pp. 855-868(14)

Publisher: Cognizant Communication Corporation

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 × 10⁷) 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.

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Keywords: Tetralogy of Fallot; Right ventricular dysfunction; Pulmonary insufficiency; Umbilical cord blood; Stem cells

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096368909X471170

Affiliations: 1: Department of Cardiac Surgery, Medical Faculty, University of Rostock, Rostock, Germany

Publication date: 2009-08-01

More about this publication?

• Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
  

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• In this Subject: Anatomy & Physiology ,  Biology ,  Biotechnology ,  Pharmacology ,  Surgery
• By this author: Yerebakan, Can ;  Sandica, Eugen ;  Prietz, Stephanie ;  Klopsch, Christian ;  Ugurlucan, Murat ;  Kaminski, Alexander ;  Abdija, Sefer ;  Lorenzen, Björn ;  Boltze, Johannes ;  Nitzsche, Björn ;  Egger, Dietmar ;  Barten, Malte ;  Furlani, Dario ;  Ma, Nan ;  Vollmar, Brigitte ;  Liebold, Andreas ;  Steinhoff, Gustav

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