Abstract: SA-PO221
The In Vitro Effect of Indoxyl Sulfate in Erythropoiesis of Human Hematopoietic Stem Cells: An Explanation of Anemia in CKD
Session Information
- Anemia and Iron Metabolism: Basic
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Anemia and Iron Metabolism
- 201 Anemia and Iron Metabolism: Basic
Authors
- Rattanasompattikul, Manoch, Golden Jubilee Medical Center, Mahidol University, Nakhon Pathom, Thailand
- Supokawej, Aungkura, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
- Promkan, Moltira, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
- Masoodi, Sumana, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand
- Rongkiettechakorn, Nuttawut, Golden Jubilee Medical Center, Mahidol University, Nakhon Pathom, Thailand
Background
The pathogenesis of anemia in chronic kidney disease (CKD) has been suggested to result from erythropoietin (EPO) insufficiency; however, several anemic CKD patients showed average to high plasma EPO levels. The presence of uremic toxins in patients with CKD has been suggested by several lines of evidence, including inhibition of erythroblast maturation. We suspected that EPO deficiency might not be the mainstay of anemia in CKD and then we focused on the effect of uremic toxins on the maturation of hematopoietic stem cells.
Methods
The effects of uremic toxin on red blood cell development was evaluated using hematopoietic stem cell (HSC) cultures. HSCs were isolated from umbilical cord blood using magnetic cell sorting to indicate CD34 positive cells. HSCs were then grown in differentiation medium combination with various concentrations of indoxyl sulfate (IS). Cell proliferation, viability, cell morphology, and erythrocyte specific markers were identified.
Results
The lower cell number in HSCs treated with IS was investigated in a dose-dependent manner. Proliferation and the percent viability of CD34 positive cells culture were observed with culture medium containing 0 (control), 25, 50, 100, and 200 ug/mL IS shown as Figure A.Erythrocyte differentiation tends to decline as demonstrated by lower numbers of CD235 and CD71 positive cells. Mature cells were counted using cell morphology assessments.
Conclusion
These findings conclude that uremic toxin (IS) appears to be a factor governing defective erythropoiesis. However, the pathogenesis of anemia involves multi-step processes that might be affected by the other types of uremic toxins and factors.
Figure A The proliferation of CD34 positive cells culture was observed for 11 days. Cells cultured with culture medium containing 0 (control), 25, 50, 100 and 200 ug/mL Indoxyl sulfate (IS)showed that all IS-treated cells decreased in cell number compared with control since day 6 of culture.
Funding
- Government Support - Non-U.S.