title: Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  Collected 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.
  
  
  CONCLUSIONS
  EPC 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.
authors.affiliation: Cellular and Molecular Imaging Laboratory, Department of Radiology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Nadimpalli Ravi S
authors.initials: NR
authors.lastname: Varma
authors.forename: Branislava
authors.initials: B
authors.lastname: Janic
authors.forename: A S M
authors.initials: AS
authors.lastname: Iskander
authors.forename: Adarsh
authors.initials: A
authors.lastname: Shankar
authors.forename: Mohammed P I
authors.initials: MP
authors.lastname: Bhuiyan
authors.forename: Hamid
authors.initials: H
authors.lastname: Soltanian-Zadeh
authors.forename: Quan
authors.initials: Q
authors.lastname: Jiang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Barton
authors.forename: Meser M
authors.initials: MM
authors.lastname: Ali
authors.forename: Ali S
authors.initials: AS
authors.lastname: Arbab
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology*; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008279:Magnetic Resonance Imaging; D010455:Peptides / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D010455:Peptides; D027981:Symporters; D000099209:Sodium-Iodide Symporters