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Effects of erythropoietin-gene electrotransfer in rats with adenine-induced renal failure
Ken Ataka1, Hiroki Maruyama, Tomohiro Neichi
1Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Background:
We previously demonstrated that erythropoietin (Epo) expression increases in five-sixths nephrectomized rats, after muscle-targeted gene transfer by in vivo electroporation, using plasmid DNA expressing rat Epo (pCAGGS-Epo). Here, we apply this method to a rat model with severe anemia associated with chronic renal failure; these rats have hematocrit levels in the 30-35% range, similar to those in humans with end-stage renal disease.
Methods:
Wistar rats were treated to produce adenine-induced uremia. The uremic rats were then treated with muscle-targeted gene transfer using pCAGGS-Epo. Some uremic rats died from chronic renal failure; one of these was dissected, and the kidneys were histologically examined. For the remaining rats, we measured body weight and blood pressure, and obtained blood samples regularly.
Results:
The uremic rats showed severe anemia, with hematocrit levels at 32.6 +/- 3.3%. Epo-gene transfer increased Epo expression and serum Epo levels, and also increased the hematocrit levels to 64.5 +/- 4.8%. The dose of pCAGGS-Epo used in this study did not induce severe hypertension.
Conclusions:
Continuous Epo-gene expression improves the anemia associated with chronic renal failure, and without severe side effects. Our results support the potential use of gene electrotransfer for human gene therapy applications.
