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Migration of Iron Oxide–labeled Human Hematopoietic Progenitor Cells in a Mouse Model: In Vivo Monitoring with 1.5-T MR Imaging Equipment¹

¹ From the Dept of Radiology (H.E.D.L., S.M., T.M.L., E.J.R.), Institute of Pathology (M.R., G.P., J.S.), IIIrd Clinic of Internal Medicine, Laboratory of Stem Cell Physiology (R.B., C.P., R.A.J.O.), and Dept of Gynecology (H.E.D.L., M.R., G.P., S.M., R.B., J.S., T.M.L., C.P., E.J.R., R.A.J.O.), Technical University, Munich, Germany; Dept of Gynecology and Obstetrics, NeuPerlach Hospital, Munich, Germany (G.D.); and Guerbet Group, Paris, France (C.C.). From the 2003 RSNA annual meeting. Received Aug 6, 2003; revision requested Oct 22; final revision received Apr 3, 2004; accepted May 3. Supported by German Research Foundation grants DA 529/1–1, the StemMat project (Bavarian Government of Health, Food, and Consumer Interests), and the Dr Ingrid Leonhard Lorenz Foundation of the Technical University of Munich. Address correspondence to H.E.D.L., Dept of Radiology, UCSF Medical Center, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 (e-mail: daldrup@radiology.ucsf.edu).

PURPOSE: To evaluate the use of clinical 1.5-T magnetic resonance (MR) imaging equipment to depict the in vivo distribution of iron oxide–labeled human hematopoietic progenitor cells in athymic mice.

MATERIALS AND METHODS: This study was approved by the ethical committee, and all women had given consent to donate umbilical cord blood for research. Twenty athymic female Balb/c mice underwent MR imaging before and 1, 4, 24, and 48 hours after intravenous injection of (1–3) x 10⁷ human hematopoietic progenitor cells labeled with the superparamagnetic iron oxide particles ferumoxides through simple incubation (n = 10) or P7228 through lipofection (n = 10). Fifteen female Balb/c control mice were examined after intravenous injection of the pure contrast agents (n = 6 for both probes) or nonlabeled cells (n = 3). Signal intensities of liver, spleen, and bone marrow on MR images obtained before and after injection were measured and compared for significant differences by using the t test. MR imaging data were compared with the results of immunostaining against human CD31⁺ cells and against the coating of the contrast agents; these results served as the standard of reference.

RESULTS: Ferumoxides was internalized into more mature CD34^– cells but not into CD34⁺ stem cells, while P7228 liposomes were internalized into both CD34^– and CD34⁺ cells. After injection of iron oxide–labeled hematopoietic cells, a significant decrease in MR signal intensity was observed in liver and spleen at 1, 4, 24, and 48 hours after injection (P < .05) and in the bone marrow at 24 and 48 hours after injection (P < .05). The signal intensity decrease in bone marrow was significantly stronger after injection of iron oxide–labeled cells compared to controls that received injections of the pure contrast agent (P < .05). Results of histopathologic examination confirmed homing of iron oxide–labeled human progenitor cells in the murine recipient organs.

CONCLUSION: The in vivo distribution of intravenously administered iron oxide–labeled hematopoietic progenitor cells can be monitored with 1.5-T MR imaging equipment.

© RSNA, 2005

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