Efficacy of cationic liposome-mediated gene transfer to mesangial cells in vitro and in vivo

Item Type:	Article
Title:	Efficacy of cationic liposome-mediated gene transfer to mesangial cells in vitro and in vivo
Creators Name:	Madry, H. and Reszka, R. and Bohlender, J. and Wagner, J.
Abstract:	Mesangial cells represent a major target for gene transfer approaches to the kidney. To establish a liposome-based system for transfection of mesangial cells we analyzed the efficacy and toxicity of different cationic liposomes and other nonviral transfection methods in primary cultures of rat and human mesangial cells using the Escherichia coli {beta}-galactosidase (lacZ) gene as a marker. In addition, an expression vector containing a human renin cDNA under the control of the cytomegalovirus immediate-early promoter/enhancer was generated, introduced into mesangial cells, and assayed in a system of transient gene expression. In vivo, gene transfer was studied after infusion of liposome/DNA complexes in the kidney of rats via the renal artery. Transfection efficiency ranged from 5.5% with DMRIE Liposomes in rat mesangial cells to 1.1% with LipofectAmine liposomes in human mesangial cells. Cytotoxicity following transfection was dependent on the transfection method. Transfection with the human renin expression vector led to the secretion of 11 pg/104 cells/48 h human renin in rat mesangial cells, 3600 pg/104 cells/48 h in 293 cells, and 113 pg/104 cells/48 h human renin in opossum kidney cells. In vivo, infusion of liposomes was accompanied by nephrotoxicity and did not result in marker gene expression. Together the data demonstrate that cationic liposomes are useful tools for transferring genes into mesangial cells, including human mesangial cells. Cationic liposomes provide a functional system for the synthesis and secretion of human renin in mesangial cells and other mammalian kidney cells. The current limitation of the evaluated liposomes for an efficient in vivo gene transfer to mesangial cells is the toxicity upon intrarenal arterial administration.
Keywords:	Cationic Liposomes, Gene Transfer, Kidney, Mesangial Cells, Animals, Rats
Source:	Journal of Molecular Medicine
ISSN:	0946-2716
Publisher:	Springer
Volume:	79
Number:	4
Page Range:	184-189
Date:	1 January 2001
Official Publication:	https://doi.org/10.1007/s001090000186
PubMed:	View item in PubMed

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