Magnetic Resonance Imaging of Mesenchymal Stem Cells Homing to Pulmonary Metastases Using Biocompatible Magnetic Nanoparticles

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 23; pp. 8862 - 8867
• Main Authors: LOEBINGER, Michael R, KYRTATOS, Panagiotis G, TURMAINE, Mark, PRICE, Anthony N, PANKHURST, Quentin, LYTHGOE, Mark F, JANES, Sam M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-2009
• Subjects: Animals; Antineoplastic agents; Biocompatible Materials - administration & dosage; Biological and medical sciences; Breast Neoplasms - pathology; Cell Line, Tumor; Ferric Compounds - administration & dosage; Humans; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Magnetic Resonance Imaging - methods; Medical sciences; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Mice; Mice, Inbred NOD; Mice, SCID; Nanoparticles - administration & dosage; Pharmacology. Drug treatments; Tumors; Xenograft Model Antitumor Assays; Nanoparticle; Stem cell; Lung; Malignant tumor; Mesenchymal cell; Metastasis; Respiratory system; Nuclear magnetic resonance imaging; Magnetic; Medical imagery; Microparticle; Biocompatibility; Homing phenomenon; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-09-1912

The ability of mesenchymal stem cells (MSC) to specifically home to tumors has suggested their potential use as a delivery vehicle for cancer therapeutics. MSC integration into tumors has been shown in animal models using histopathologic techniques after animal sacrifice. Tracking the delivery and engraftment of MSCs into human tumors will need in vivo imaging techniques. We hypothesized that labeling MSCs with iron oxide nanoparticles would enable in vivo tracking with magnetic resonance imaging (MRI). Human MSCs were labeled in vitro with superparamagnetic iron oxide nanoparticles, with no effect on differentiation potential, proliferation, survival, or migration of the cells. In initial experiments, we showed that as few as 1,000 MSCs carrying iron oxide nanoparticles can be detected by MRI one month after their coinjection with breast cancer cells that formed subcutaneous tumors. Subsequently, we show that i.v.- injected iron-labeled MSCs could be tracked in vivo to multiple lung metastases using MRI, observations that were confirmed histologically. This is the first study to use MRI to track MSCs to lung metastases in vivo. This technique has the potential to show MSC integration into human tumors, allowing early-phase clinical studies examining MSC homing in patients with metastatic tumors.