Abstract
BackgroundDue to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities.Methods and ResultsCollected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m) in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS). Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors.ConclusionEPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for glioma therapy as well as imaging probes.
Highlights
Endothelial Progenitor Cells (EPCs) can be used as gene carrier/delivery system for glioma therapy as well as imaging probes
Due to their unique property to migrate to pathological lesions, stem cells are considered to be used as a delivery vehicle for therapeutic genes to tumors, especially for glioma [1,2]
Low signal intensities detected by magnetic resonance imaging (MRI) enabled tracking of administered cells while increased uptake of Tc-99m in tumors, detected by in vivo single photon emission computed tomography (SPECT), indicated functional expression of transgene after incorporation of EPCs in glioma
Summary
Due to their unique property to migrate to pathological lesions, stem cells are considered to be used as a delivery vehicle for therapeutic genes to tumors, especially for glioma [1,2]. Investigators have used neural and mesenchymal stem cells as vehicles for delivering cytotoxic or therapeutic genes [1,3,4] These cells were administered either locally or systemically. Based on EPCs’ characteristics, it is possible to use these cells as carriers or delivery vehicles for therapeutic genes to tumors or glioma, which can be administered either systemically or locally. These EPCs can be collected from patients’ peripheral blood. Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities
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