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Open Access The Presence of Apoptotic Bone Marrow Cells Impairs the Efficacy of Cardiac Cell Therapy

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Abstract:

Injection of autologous bone marrow cells into infarcted myocardium has been proposed to limit the deterioration of cardiac function following myocardial infarction (MI); unfortunately, the beneficial effects observed have been modest. One of the limiting factors is believed to be poor local survival of the injected cells, but the potential impact of apoptosis among the injected cells has yet to be assessed. Therefore, this study aimed to quantify the apoptosis rate in bone marrow mononuclear cells (BMMCs) prepared for cardiac therapy, and to analyze their effects in vitro on cardiomyoblast apoptosis and in vivo on cardiac function recovery following MI. Using rabbit BMMCs prepared by Ficoll gradient, apoptotic cells were detected via Annexin V (AnV) staining. The effects of depleting the apoptotic cell population by means of AnV magnetic beads was tested in vitro after coculture with cardiomyoblasts (H9c2 cells) and in vivo after cell injection into the infarcted area. Left ventricular ejection fraction and scar extent were assessed by echography and histology 2 months later. After Ficoll gradient isolation, 37.3% (33.4‐37.9%) of BMMCs were found to be apoptotic (ApoBase BMMCs). AnV depletion decreased the proportion of apoptotic cells to 20% (17.6‐32%) (ApoLow BMMCs). Rabbits treated in vivo with ApoLow BMMCs after MI presented with significantly improved left ventricular ejection fraction [41.4% (41.0‐43.6%) vs. 34.6% (34.6‐35.9%), p = 0.03), reduced scar extent [20.4% (17.9‐24.3%) vs. 25.6% (17.9‐27.9%), p = 0.057], and reduced rate of cardiomyocyte apoptosis compared to those treated with ApoBase BMMCs. H9c2 apoptosis was found to be higher after coculture with ApoBase than with ApoLow BMMCs [25.6% (22.6‐29.6%) vs. 10.1% (6.6‐12.6%), p = 0.03], a result partially reproduced by cocultures with microparticle-rich supernatants from BMMCs. The presence of apoptotic cells among BMMCs impairs the efficacy of cardiac cell therapy after MI, an effect possibly mediated by apoptotic microparticles.

Keywords: Annexin V; Apoptosis; Bone marrow; Cell sorting; Cell therapy; Myocardial infarction

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368910X544924

Affiliations: Université Lille Nord de France, EA 2693, Lille, France

Publication date: July 1, 2011

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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