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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB001847-01
Application #
6708793
Study Section
Special Emphasis Panel (ZRG1-F05 (50))
Program Officer
Pastel, Mary
Project Start
2003-09-15
Project End
2005-08-31
Budget Start
2003-09-15
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$229,500
Indirect Cost
Name
Case Western Reserve University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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