Document Type thesis Author Name Fakharzadeh, Michael URN etd-050310-111607 Title Delivering Stem Cells to the Heart Degree MS Department Biomedical Engineering Advisors Glenn Gaudette, Advisor George Pins, Committee Member Marsha Rolle, Committee Member Keywords heart attack microthreads hMSC myocardial infarction Date of Presentation/Defense 2010-05-03 Availability unrestricted
Myocardial infarction is a prominent medical problem in the world today. Current treatments are limited and do not strive to regenerate the myocardial tissue that is lost post-infarction. Human mesenchymal stem cells (hMSCs) have been shown to improve cardiac function when implanted post-infarction. The effectiveness of stem cell therapy largely depends on the delivery method. Current delivery methods are insufficient due to their low cell engraftment rate and inability to target the endocardium, where most myocardial infarctions occur. Biological microthreads are a promising new local cell delivery method that may improve upon these current limitations. We hypothesize that biological microthreads will increase efficiency of hMSC delivery to the beating rat heart compared to intramyocardial injection. To test our hypothesis we seeded biological microthreads in vitro with 100 ìL of cell suspension (100,000 hMSCs). After one day, an average of 11,806 ± 3,932 hMSCs were counted on the biological microthreads. The biological microthreads were attached to suture needles to allow targeted delivery to the rat heart (in the left ventricular wall). Human mesenchymal stem cells were loaded with quantum dots prior to seeding the biological microthread bundles or delivery to the rat heart via injection. For intramyocardial injection, a cell suspension containing 10,000 hMSCs (35 ìL) was injected into the myocardial wall using a 100 ìL syringe. The delivery efficiency of each method was determined by sectioning the heart into 8 µm thick sections and analyzing three sections every sixty sections (24 µm every 480 µm) for quantum dot loaded hMSCs. These sections were stained with Hoechst dye and quantum dot loaded cells in the heart sections were manually counted. The delivery efficiency of each biological microthread implantation was calculated by dividing the number of counted quantum dot loaded hMSCs in the heart wall by the average number of hMSCs on the biological microthread bundles (normalized to the length that was implanted in the heart wall) after 24 hours. The delivery efficiency of intramyocardial injection was calculated by dividing the number of counted quantum dot loaded hMSCs in the heart wall by 10,000 (the number of cells injected). Biological microthread mediated hMSC delivery had a significantly higher delivery efficiency (66.6 ± 11.1%) compared to intramyocardial injection (11.8 ± 6.25%) after 1 hour (p < 0.05). Biological microthread implantation tracking illustrated that we were able to deliver hMSCs to the myocardium and endocardium of the left ventricular wall for hMSC delivery. This study illustrates that biological microthreads can serve as an efficient means of delivering hMSCs to the infarcted heart. Unlike the currently utilized delivery methods, biological microthreads can target the infarcted layer of the left ventricular wall and maximize hMSC engraftment to that layer.
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