Encapsulated transgene cells attenuate hypertension, cardiac hypertrophy and enhance renal function in Goldblatt hypertensive rats.
BACKGROUND
The success of any gene-therapy approach depends on the survival of the genetically engineered cells that are implanted in the patient to deliver the therapeutic product. Immunoisolation of nonautologous cells within a microcapsule is a unique approach for gene therapy.


METHODS
We employed an immunoisolation device that protects nonautologous cells from destruction, to implant human atrial natriuretic peptide (hANP)-producing Chinese hamster ovary (CHO) cells in two-kidney, one-clip (2K1C) hypertensive rats. CHO cells transfected with the plasmid CMV-cANP were encapsulated in biocompatible polycaprolactone (PCL) capsules, and then the PCL capsules were implanted into 2K1C hypertensive rats intraperitoneally.


RESULTS
The implantation of encapsulated hANP-producing cells caused a significant delay of blood pressure (BP) increase 2 weeks post-implantation and the effect lasted for more than 5 months. The implantation of encapsulated hANP-producing cells also caused significant increases in renal blood flow (RBF), glomerular filtration rate (GFR), sodium output, urine excretion, and urinary cGMP levels. These beneficial effects were reflected morphologically by an attenuation of the glomerular sclerotic lesions, reduction in cardiomyocyte size, tubular injury and renal arterial thickening. Immunoreactive hANP can be detected in the blood of 2K1C rats after implantation of the PCL capsules containing hANP-producing cells.


CONCLUSIONS
This study demonstrates the usefulness of encapsulated ANP gene transfected cells as a new tool for ANP gene delivery in studying renovascular hypertension and cardiovascular diseases. Thus, our results may have important implications for clinical use of transgene cells as therapeutic agents in the treatment of cardiovascular diseases.
Chen
Li-Guo
LG
School of Basic Medicine and Forensics, Sichuan University, Chengdu, 610041, P.R. China.
Wang
Zheng-Rong
ZR
Wan
Chao-Min
CM
Chao
Lee
L
Chao
Julie
J
Xing
Hao-Yang
HY
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics*; D001794:Blood Pressure; D016466:CHO Cells; D006332:Cardiomegaly / Q000628:therapy*; D006224:Cricetinae; D006973:Hypertension / Q000628:therapy*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D018613:Microscopy, Confocal; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D019076:Transgenes
D009320:Atrial Natriuretic Factor