In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction

The therapeutic potential of administering stem cells to promote angiogenesis and myocardial tissue regeneration after infarction has recently been demonstrated. Given the advantages of using embryonic stem cells and mouse models of myocardial infarction for furthering the development of this therapeutic approach, the purpose of this study was to determine if embryonic stem cells could be loaded with superparamagnetic iron oxide (SPIO) particles and imaged in a mouse model of myocardial infarction over time using MRI. Mouse embryonic stem cells were labeled with SPIO particles. When incubated with 11.2, 22.4, and 44.8 μg Fe/ml of SPIO particles, cells took up increasing amounts of iron oxide. Embryonic stem cells loaded with SPIO compared to unlabeled cells had similar viability and proliferation profiles for up to 14 days. Free SPIO injected into infarcted myocardium was not observable within 12 hr after injection. After injection of three 10‐μl aliquots of 107 SPIO‐loaded cells/ml into infarcted myocardium, MRI demonstrated that the mouse embryonic stem cells were observable and could be seen for at least 5 weeks after injection. These findings support the ability of MRI to test the long‐term therapeutic potential of embryonic stem cells in small animals in the setting of myocardial infarction. Magn Reson Med 52:1214–1219, 2004. © 2004 Wiley‐Liss, Inc.

[1]  Jeff W M Bulte,et al.  Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques , 2003, Transplantation.

[2]  D. Ganten,et al.  Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning , 2002, Nature Medicine.

[3]  A. Kosaki,et al.  Implantation of Bone Marrow Mononuclear Cells Into Ischemic Myocardium Enhances Collateral Perfusion and Regional Function via Side Supply of Angioblasts, Angiogenic Ligands, and Cytokines , 2001, Circulation.

[4]  Bruce G. Jenkins,et al.  Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Yong-Fu Xiao,et al.  Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells. , 2003, The Journal of thoracic and cardiovascular surgery.

[6]  S. Homma,et al.  Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function , 2001, Nature Medicine.

[7]  C. W. Jung Surface properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[8]  Jeff W M Bulte,et al.  Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. , 2003, Radiology.

[9]  J A Frank,et al.  Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: Relationship between relaxivities, electrostatic forces, and chemical composition , 2003, Magnetic resonance in medicine.

[10]  R. Chandra,et al.  Theory of nonexponential NMR signal decay in liver with iron overload or superparamagnetic iron oxide particles , 2002, Magnetic resonance in medicine.

[11]  J. Jensen,et al.  Strong field behavior of the NMR signal from magnetically heterogeneous tissues , 2000, Magnetic Resonance in Medicine.

[12]  J. Morgan,et al.  Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. , 2002, Journal of applied physiology.

[13]  B. Nordén,et al.  Characterization of interaction between DNA and 4',6-diamidino-2-phenylindole by optical spectroscopy. , 1987, Biochemistry.

[14]  F. Gámiz,et al.  Electron transport in strained Si inversion layers grown on SiGe-on-insulator substrates , 2002 .

[15]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[16]  Jérôme Garot,et al.  Magnetic resonance imaging of targeted catheter-based implantation of myogenic precursor cells into infarcted left ventricular myocardium. , 2003, Journal of the American College of Cardiology.

[17]  P. Jacobs,et al.  Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[18]  J. Reig,et al.  Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. , 2000, Diabetes.

[19]  Susan Budavari,et al.  The Merck index : an encyclopedia of chemicals, drugs, and biologicals , 1983 .

[20]  Ergin Atalar,et al.  In Vivo Magnetic Resonance Imaging of Mesenchymal Stem Cells in Myocardial Infarction , 2003, Circulation.