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Blood, 1 January 2005, Vol. 105, No. 1, pp. 420-425.
Prepublished online as a Blood First Edition Paper on August 26, 2004; DOI 10.1182/blood-2004-06-2222.
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TRANSPLANTATION
Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model
Stasia A. Anderson,
John Glod,
Ali S. Arbab,
Martha Noel,
Parwana Ashari,
Howard A. Fine, and
Joseph A. Frank
From the Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; the Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; and the Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD.
Bone marrow-derived endothelial precursor cells incorporate into neovasculature and have been successfully used as vehicles for gene delivery to brain tumors. To determine whether systemically administered Sca1+ bone marrow cells labeled with superparamagnetic iron oxide nanoparticles can be detected by in vivo magnetic resonance imaging in a mouse brain tumor model, mouse Sca1+ cells were labeled in vitro with ferumoxides-poly-L-lysine complexes. Labeled or control cells were administered intravenously to glioma-bearing severe combined immunodeficient (SCID) mice. Magnetic resonance imaging (MRI) was performed during tumor growth. Mice that received labeled cells demonstrated hypointense regions within the tumor that evolved over time and developed a continuous dark hypointense ring at a consistent time point. This effect was not cleared by administration of a gadolinium contrast agent. Histology showed iron-labeled cells around the tumor rim in labeled mice, which expressed CD31 and von Willebrand factor, indicating the transplanted cells detected in the tumor have differentiated into endothelial-like cells. These results demonstrate that MRI can detect the incorporation of magnetically labeled bone marrow-derived precursor cells into tumor vasculature as part of ongoing angiogenesis and neovascularization. This technique can be used to directly identify neovasculature in vivo and to facilitate gene therapy by noninvasively monitoring these cells as gene delivery vectors. (Blood. 2005;105:420-425)
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