Concise review: Mesenchymal stem cell tumor-homing: detection methods in disease model systems

Abstract

Despite the decline in U.S. cancer incidence and mortality rates, cancer remains the number one cause of death for people under the age of 85 and one in four people in the U.S. will die of cancer, mainly because of metastasis. Recently, interest in mesenchymal stem cell (MSC) tumor-homing has led to inquires into: (a) why MSCs home to tumors, (b) what the inherent protumor and antitumor consequences are, and (c) how to best capitalize on MSC tumor-homing for cell-based diagnostics and therapy. Here, these questions are reviewed and method for addressing them using animal models and tracking methodologies (or, synonymously, detection methodologies) are discussed. First, MSCs in a regenerative and tumor-homing context are reviewed, followed by MSC delivery and genetic labeling methods for tissue model systems. Finally, the use of the nonoptical methods, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, along with optical methods, fluorescence imaging and bioluminescent imaging, are reviewed related to tracking MSCs within disease model settings. The benefits and drawbacks of each detection method in animal models is reviewed along with the utility of each for therapeutic use.

Figure 1

Imaging modalities for MSC-tumor tropism. A) Flow cytometry plot of cells from a single cell suspension of a digested primary tumor containing three populations of cells (Tumor cells, MSCs, and residual mouse mammary cells.) B) eGFP fluorescent MSCs (green) and glioma tumor cells (red) identified using epifluorescence microscopy of tumor sections show co-localization within tumor. Bar = 100 μm. C) Whole-chromosome FISH painting identifies Y chromosomes (red) from male rat MSCs within female-derived glioma tumors. Nuclei are stained with by DAPI (4′,6-diamidino-2-phenylindole staining) (blue). Scale bar = 15 μm. D) Xenogen images demonstrate the use of BLI to track fLuc-expressing MSC homing from tail-vein specifically to primary orthotopic 4T1 breast tumors (below) compared to non-cancerous mammary fat pads (above). E) Intravenously-delivered SPIO-loaded MSCs localize to lung metastases and can be visualized by MRI. 1, Normal lung. 2,5) Lung with MDA-MB-231 metastases. 3,6) Same lung 1 hr after SPIO-loaded MSC injection shows decreased MRI signal in metastases signal. 4) H&E histologic sections (bar, 100 μm). See references for more details. Figure 1A (unpublished data from our lab). Figures 1B and 1C from Reference , Figure 1D and 1E adapted and reprinted by permission from the American Association for Cancer Research from references and respectively.