Although therapeutic applications of mesenchymal progenitor cells (MPCs) have been studied, the in vivo fate of genes delivered by the MPCs has received little attention. We report here the in vivo kinetics, tissue distribution, and duration of gene expression after systemic administration of plasmid DNA delivered by MPCs. Murine MPCs were isolated from bone marrow, cultured, and transfected with plasmid DNA using polyethylenimine. The gene-modified MPCs or naked plasmid DNA was administered intravenously to mice. Injected MPCs incorporating plasmid DNA yielded elevated serum concentrations when compared with the group treated with plasmid DNA alone, a 280-fold higher level measured at 5-min post-administration. Moreover, plasmid DNA delivered in MPCs was detected in several organs, lymph nodes, and bone marrow. The highest levels of distribution were observed in the liver, followed by lung and spleen at 4 days post-dose. Similar to the distribution of DNA, significant expression levels of the exogenous gene were observed only after delivery of the DNA in MPCs, demonstrating the sustained expression at the liver, lung, and kidney for 4 days after tail vein injection. This study provides perspectives regarding the in vivo fate and target tissue distribution of genes following MPC-based delivery.
Bibliographical noteFunding Information:
Funding. This study was financially supported by grants from the Ministry of Science and Technology (F104AA010003-07A0101-00310), Korea; the Basic Research Program of Korea Science and Engineering Foundation (KOSEF R01-2005-000-10292-0); and the SRC program (R11-2005-008-00000-0) of MOST/KOSEF through the Center for Intelligent Nano-Bio Materials at Ewha Womans University.
- Gene delivery vehicles
- Mesenchymal progenitor cells
- Plasmid DNA
ASJC Scopus subject areas
- Pharmaceutical Science