Effects of recombinant human erythropoietin on hematopoietic progenitors of chronic hemodialysis patients in vitro and in vivo

1989 ◽  
Vol 7 (4) ◽  
pp. 257-263 ◽  
Author(s):  
Masayuki Hino ◽  
Kohei Miyazono ◽  
Akio Urabe ◽  
Fumimaro Takaku
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis ◽  
Hematopoietic Progenitors ◽  
Human Erythropoietin

scholarly journals Effect of Zinc Supplementation on Renal Anemia in 5/6-Nephrectomized Rats and a Comparison with Treatment with Recombinant Human Erythropoietin

2019 ◽  
Vol 20 (20) ◽  
pp. 4985 ◽  
Author(s):  
Hui-Lin Feng ◽  
Yen-Hua Chen ◽  
Sen-Shyong Jeng
Keyword(s):  
Bone Marrow ◽  
Recombinant Human Erythropoietin ◽  
Zinc Supplementation ◽  
Bone Marrow Cells ◽  
Human Erythropoietin ◽  
Post Surgery ◽  
Rat Bone ◽  
Marrow Cells

Anemia is a severe complication in patients with chronic kidney disease (CKD). Treatment with exogenous erythropoietin (EPO) can correct anemia in many with CKD. We produced 5/6-nephrectomized rats that became uremic and anemic at 25 days post surgery. Injection of the anemic 5/6-nephrectomized rats with 2.8 mg zinc/kg body weight raised their red blood cell (RBC) levels from approximately 85% of the control to 95% in one day and continued for 4 days. We compared the effect of ZnSO4 and recombinant human erythropoietin (rHuEPO) injections on relieving anemia in 5/6-nephrectomized rats. After three consecutive injections, both the ZnSO4 and rHuEPO groups had significantly higher RBC levels (98 ± 6% and 102 ± 6% of the control) than the saline group (90 ± 3% of the control). In vivo, zinc relieved anemia in 5/6-nephrectomized rats similar to rHuEPO. In vitro, we cultured rat bone marrow cells supplemented with ZnCl2, rHuEPO, or saline. In a 4-day suspension culture, we found that zinc induced erythropoiesis similar to rHuEPO. When rat bone marrow cells were supplement-cultured with zinc, we found that zinc stimulated the production of EPO in the culture medium and that the level of EPO produced was dependent on the concentration of zinc supplemented. The production of EPO via zinc supplementation was involved in the process of erythropoiesis.

Long-Term Effects of Recombinant Human Erythropoietin on Macro-and Microcirculation in Chronic Hemodialysis Patients

1993 ◽  
Vol 11 (4) ◽  
pp. 237-247 ◽  
Author(s):  
J.J.J.M. Wirtz ◽  
K.M.L. Leunissen ◽  
W. van Kuijk ◽  
E.C. Cheriex ◽  
D.W. Slaaf ◽  
...  
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis ◽  
Long Term Effects ◽  
Human Erythropoietin

scholarly journals 225 RECOMBINANT HUMAN ERYTHROPOIETIN PRODUCED IN THE MILK OF TRANSGENIC MICE: FUNCTIONAL CHARACTERIZATION AND PHARMACEUTICAL APPROACH

2005 ◽  
Vol 17 (2) ◽  
pp. 263
Author(s):  
D.N. Kwon ◽  
J.Y. Park ◽  
S.Y. Lee ◽  
S.J. Kang ◽  
J.H. Kim
Keyword(s):  
Mammary Gland ◽  
Transgenic Mouse ◽  
Cho Cells ◽  
Recombinant Human Erythropoietin ◽  
Mouse Mammary Gland ◽  
Human Erythropoietin ◽  
Mouse Milk ◽  
Bioreactor System

The proper post-transcriptional modification of recombinant human erythropoietin (rhEPO) is critical to retain its biological functions, either in vivo or in vitro. The major glycosyltransferases for the determinant of glycosylation patterns of rhEPO are N-acetylglycosaminyltransferase (GnT) and α-1-3/4 fucosyltransferase (Fut). GnT-III expression (388 ± 19.09) in the mouse mammary gland has been shown to be dramatically different from that in CHO cells, although FuT-VIII expression in CHO cells (1970 ± 255.9) is comparable to mouse mammary gland (272 ± 14.8), suggesting that the mammary gland may proceed with the proper glycosylation of rhEPO as shown in CHO cells. To identify this hypothesis and establish the rhEPO bioreactor system for mass production of protein in transgenic animals, we have generated two transgenic mouse lines that express rhEPO in milk. Both lines of transgenic mouse express only rhEPO in the lactating mammary gland, and the protein yield of rhEPO in lactating milk is comparable to that in CHO cells. After determining the protein expression in lactating milk, using three different methods – enzymatic release of oligosaccharide analysis, two-dimensional electrophoresis, and 2-aminobenzamide-labeled analysis – we report that the rhEPO produced by the animal bioreactor system has the proper glycosylation patterns as shown in CHO cell-derived Epoietin α, and has more tetra-acidic oligosaccharide structures than Epoietin α, which is the widely used rhEPO for therapeutic purposes. The in vitro biological property of transgenic mouse milk-derived rhEPO has been tested by measuring luciferase activity in MCF-7 cells, indicating that rhEPO from mammary gland up-regulates the EPO-receptor-mediated STAT5 gene expression in a dose-dependent manner the same as Epoietin α does. In addition, in vivo biological activity demonstrated that direct injection of rhEPO into a mouse vein increases blood components such as RBC and HCT. In light of these findings, we suggest that high levels of tetra-acidic structures observed in transgenic mouse milk-derived rhEPO may be related to the high level of expression of glycosiltransferases (GnT-III and FuT-VIII) in mammary gland; thus the bioreactor system using the mammary gland of a transgenic animal could be a good candidate for production of rhEPO for pharmaceutical purposes. This work was supported in part by a grant program from RDA(Biogreen21) and Cho-A, Republic of Korea. D.N. Kwon is the recipient of a scholarship from the BK21 program, granted by the Ministry of Education, Korea.

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