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Intramyocardial Delivery of Bone Marrow Mononuclear Cells and Mechanical Assist Device Implantation in Patients With End-Stage Cardiomyopathy

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Abstract:

In end-stage heart failure, mechanical ventricular assist devices (VAD) are being used as bridge-to-transplantation, as a bridge-to-recovery, or as the definitive therapy. We tested the hypothesis that myocardial implantation of autologous bone marrow mononuclear cells (BMNC) increases the likelihood of successful weaning from left VAD (LVAD) support. Ten patients (aged 14–60 years) with deteriorating heart function underwent LVAD implantation and concomitant implantation of autologous BMNC. Bone marrow was harvested prior to VAD implantation and BMNC were prepared by density centrifugation. Two patients received a pulsatile, extracorporeal LVAD and eight a nonpulsatile implantable device. Between 52 and 164 × 107 BMNC containing between 1 and 12 × 106 CD34+ cells were injected into the LV myocardium. There was one early and one late death. The median time on LVAD support was 243 days (range 24–498 days). Repeated echocardiographic examinations under increased hemodynamic load revealed a significant improvement of LV function in one patient. Three patients underwent heart transplantation, and four patients remain on LVAD support >1 year without evidence of recovery. Only one patient was successfully weaned from LVAD support after 4 months, and LV function has remained stable ever since. In patients with end-stage cardiomyopathy, intramyocardial injection of BMNC at the time of LVAD implantation does not seem to increase the likelihood of successful weaning from VAD support. Other cell-based strategies should be pursued to harness the potential of cell therapy in LVAD patients.

Keywords: Assist device; Bone marrow; Heart failure; Myocardium; Regeneration; Surgery

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368907783338235

Affiliations: 1: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany 2: Department of Anesthesiology, Deutsches Herzzentrum Berlin, Berlin, Germany 3: Pediatric Bone Marrow Transplant Program, Charité, Universitätsmedizin Berlin, Berlin, Germany 4: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany, BCRT—Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany

Publication date: September 1, 2007

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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