Human bone marrow derived stem cells are able to proliferate extensively in vitro without loss of differentiation potential in vitro. They represent a novel cellular therapy of inherited or degenerative diseases. We want to investigate the interaction between bone marrow derived mesenchymal stem cells (MSC) and the hematopoietic stem cells (HSC) to determine if MSCs could support allogeneic HSC transplantation by facilitating engraftment without increasing the risk of graft versus host disease (GVHD). However, there is insufficient information about in vivo distribution and survival of intravenously infused human stem cells and, their contribution to normal tissue function. Thus far, it has not been feasible to reliably track these infused cells in vivo and in real-time in neither pre-clinical nor clinical studies. In this application, we propose to develop molecular imaging techniques to track intravenously infused cells in vivo at multiple time points to understand their distribution and proliferation. Specifically, we propose to use Na+/I- symporter (NIS) gene as a reporter gene to tag human stem cells for imaging their distribution and persistence in vivo by using radioiodide or pertechnetate as the tracer. NIS is an intrinsic membrane glycoprotein that mediates active iodide (I-) uptake into thyroid follicular cells. It has been shown that NIS gene transfer can induce iodide uptake in a variety of cells and that xenografts expressing exogenous NIS could be imaged in vivo. Our previous experience with MSC and HSC infusion and NIS gene imaging will ensure the success of this project. When developed, the proposed in vivo imaging technology will give us insights into human stem cell's potentials. We will first test the feasibility of NIS gene transduction and then develop the imaging techniques with radioiodide or equivalent for monitoring stem cell infusion. Although our focus is on human MSCs and HSCs, other stem/progenitor cells can also be studied using the proposed technology. This non-invasive approach that can be used for repeated imaging will also enable us to extend our hematology/oncology research beyond MSC or other stem cell transplantation.
| Wang, Fangjing; Dennis, James E; Awadallah, Amad et al. (2009) Transcriptional profiling of human mesenchymal stem cells transduced with reporter genes for imaging. Physiol Genomics 37:23-34 |
| Lee, Zhenghong; Dennis, James E; Gerson, Stanton L (2008) Imaging stem cell implant for cellular-based therapies. Exp Biol Med (Maywood) 233:930-40 |
| Lin, Yuan; Molter, Joe; Lee, Zhenghong et al. (2008) Bioluminescence imaging of hematopoietic stem cell repopulation in murine models. Methods Mol Biol 430:295-306 |
| Love, Zachary; Wang, Fangjing; Dennis, James et al. (2007) Imaging of mesenchymal stem cell transplant by bioluminescence and PET. J Nucl Med 48:2011-20 |
