Modulation of biodistribution and expression of plasmid DNA following mesenchymal progenitor cell-based delivery.
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.
School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
Young-Sin
YS
Jeong
Eun Joong
EJ
Kim
Chang-Koo
CK
Shim
Joon Hyuk
JH
Hou
Jung Mogg
JM
Kim
Han-Gon
HG
Choi
Won-Ki
WK
Kim
Yu-Kyoung
YK
Oh
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage* / Q000096:biosynthesis / Q000493:pharmacokinetics*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D007262:Infusions, Intravenous; D059630:Mesenchymal Stem Cells; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D011094:Polyethyleneimine; D016133:Polymerase Chain Reaction; D014018:Tissue Distribution
D011094:Polyethyleneimine; D004247:DNA