The Effect of Baicalin as A PPAR Activator on Erythroid Differentiation of CD133(+) Hematopoietic Stem Cells in Umbilical Cord Blood

Abstract

Objective: The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins whose functions as transcription factors regulate gene expressions. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. This study attempts to determine the effect of baicalin, a PPAR gamma activator, on erythroid differentiation of cluster of differentiation 133(+) (CD133(+)) cord blood hematopoietic stem cells (HSCs). Materials and Methods: In this experimental study, in order to investigate the effects of the PPAR gamma agonists baicalin and troglitazone on erythropoiesis, we isolated CD133(+) cells from human umbilical cord blood using the MACS method. Isolated cells were cultured in erythroid-inducing medium with or without various amounts of the two PPAR gamma activators (baicalin and troglitazone). Erythroid differentiation of CD133(+) cord blood HSCs were assessed using microscopic morphology analysis, flow cytometric analysis of erythroid surface markers transferrin receptor (TfR) and glycophorin A (GPA) and bycolony forming assay. Results: Microscopic and flow cytometric analysis revealed the erythroid differentiation of CD133* cord blood HSCs under applied erythroid inducing conditions. Our flow cytometric data showed that the TfR and GPA positive cell population diminished significantly in the presence of either troglitazone or baicalin. The suppression of erythroid differentiation in response to PPAR gamma agonists was dose-dependent. Erythroid colony-forming ability of HSC decreased significantly after treatment with both PPAR gamma agonists but troglitazone had a markedly greater effect. Conclusion: Our results have demonstrated that PPAR gamma agOnists modulate erythroid differentiation of CD133(+) HSCs, and therefore play an important role in regulation of normal erythropoiesis under physiologic conditions. Thus, considering the availability and application of this herbal remedy for treatment of a wide range of diseases, the inhibitory effect of baicalin on erythropoiesis should be noted.