Transcatheter Injection-Induced Changes in Human Bone Marrow-Derived Mesenchymal Stem Cells
Abstract:Human mesenchymal stem cells (hMSC) are being administered by direct intramyocardial (IM) injection into patients with myocardial dysfunction with an objective to improve clinical status. However, surprisingly little attention has been directed to qualifying hMSC functionality beyond simple viability. In particular, the transit of hMSCs through a small-caliber needle lumen, the final fluidic pathway for all IM injection devices, may be especially prone to inducing unwarranted effects on cell function. This study evaluated the changes in clonogenicity, gene expression, and cytokine secretion that may be induced in hMSC (20 million/ml) by injection through a 26-gauge Nitinol needle at two different flow rates compared to noninjected control samples. Results indicated that hMSC viability and colony forming unit (CFU) formation was not altered by changes in injection rate, although a trend toward lower titers was noted at the higher flow rate, for the specific batch of hMSCs studied. The gene expression and cytokine analysis data suggest that delivering a suspension of MSCs through narrow lumen needles may marginally alter certain gene expression programs, but that such in vitro effects are transient and not translated into measurable differences in protein production. Gene expression levels of four cytokines (bFGF, SDF-1, SCF, VEGF) were significantly different at 400 l/min, and that of all cytokines were significantly different at 1600 l/min when compared to controls (p < 0.05). These changes were less pronounced (statistically insignificant for most cases, p > 0.05) and, in certain instances directionally opposite, at 72 h. However, no differences in the amounts of secreted bFGF, VEGF, or TGF- were detectable at either of the two time points or flow rates. We infer that intramyocardial administration by transcatheter techniques is unlikely to interfere with the machinery required for cell replication or secretion of regulatory and other growth factors, which are the mainstays of MSC contribution to cardiac tissue repair and regeneration.
Document Type: Research Article
Affiliations: Abbott Vascular, Santa Clara, CA, USA
Publication date: 2009-10-01
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.