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

Abstract

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. [Cancer Res 2009;69(23):8862-7]

Stem Cells and Cell Therapies in Lung Biology and Diseases: Conference Report

“…Dr. Janes presented data showing that lentiviral vectors can be used to transduce MSCs effectively and safely. Using this system, he discussed studies using MSCs engineered to express the proapoptotic molecule TRAIL in an inducible manner using the TET-ON regulation system to kill cancer cells both in vitro and in vivo in a mouse model of metastatic lung disease (96)(97)(98). Further discussion focused on the regulatory hurdles and advancements needed to translate this novel type of antitumor therapy in the clinical setting (96).…”

TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells

“…7 Tumor-directed migration and incorporation of MSCs have been demonstrated in a number of preclinical studies in vitro using transwell migration assays, and in vivo using animal tumor models. The homing capacity of MSCs has been demonstrated with almost all tested human cancer cell lines, including lung cancer, 8 malignant gliomas, 9--11 Kaposi's sarcomas, 12 breast cancer, 13,14 colon carcinoma, 15 pancreatic cancer, 16,17 melanoma 18 and ovarian cancer. 13 Engineered with tumor-specific anticancer genes, MSCs are capable of producing anticancer agents locally and constantly at the tumor site.…”

Suppression of IL‐8‐Src signalling axis by 17β‐estradiol inhibits human mesenchymal stem cells‐mediated gastric cancer invasion

“…Mesenchymal stem cells (MSCs) as an important population of cells that contribute to tumour progression and drug resistance 1, 2. Mesenchymal stem cells can migrate to the damaged tissue and the microenvironment of developing gastric tumour 3, in which MSCs might promote tumour malignance through tumour growth, invasion, metastasis formation and therapy resistance, through paracrine secretion of cytokines, chemokines, growth factors and the differentiation of MSCs into tumour‐associated fibroblasts 1, 4, 5, 6.…”