Abstract 16456: Enhanced Cardiac Stem Cell Engraftment with Magnetic Gadonanotubes
Adult bone marrow-derived mesenchymal stem cells (MSCs) are attractive for cellular cardiomyoplasty because of their multipotent nature and immunomodulatory properties. However, low engraftment and survival of transplanted cells remain as major challenges and limit the efficacy of stem cell therapy. Single-walled carbon nanocapsules known as the Gadonanotubes (GNTs) have previously been demonstrated as an effective cell tracking label. In addition to being a high-performance T1-weighted MRI contrast agent, GNTscan readily be internalized by MSCs and render cells magnetically active. We hypothesize that GNTs can enhance MSC engraftment at target sites in the presence of an external magnetic field. MSCs were either labeled with GNTs or diamagnetic colloidal Lutetium (control). Left thoracotomy was performed on female juvenile pigs (n=24) under general anesthesia. A sterilized 1.3T NdFeB ring magnet was sutured onto the left ventricular anterior wall, and epicardial cell injections were localized around the inner and outer perimeters of the ring magnet. Upon euthanasia, the left ventricle, right ventricle, and surrounding lymph nodes were collected for elemental analysis (Gd, Lu) using inductively-coupled plasma mass spectrometry (ICP-MS) to quantify the number of engrafted cells in each sample.To assess cell retention and biocompatibility of GNT-labeled MSCs in the presence of a sutured magnet, we tested different cell doses, times of magnet exposure and endpoints. Preliminary results indicate that the sutured magnet assists in retaining up to three times more GNT-labeled MSCs than Lu-labeled cells, irrespective of magnet exposure or sacrifice times. The animals tolerated the implanted strong magnet for up to 30 days; however, signs of an inflammatory response to the magnet were observed after 48 hours. In conclusion, GNTs have enhanced MSC engraftmentat target sites as a result from the placement of an external magnetic source.This constitutes a novel approach that may improve the efficacy of cellular cardiomyoplasty. In addition to safety and efficacy evaluation, the future work will focus on making this technology minimally invasive and detecting the engrafted GNT-labeled MSCs by MRI.
- © 2012 by American Heart Association, Inc.