Comparative Evaluation of Hormones and Hormone-Like Molecule in Lineage Specification of Human Induced Pluripotent Stem Cells

BACKGROUND AND OBJECTIVES: Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification. METHODS AND RESULTS: We used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34⁺CD45⁺ cells with progenitor functions, even in the CD43⁻ population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision. CONCLUSIONS: Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.

The Usefulness of CO2 Indirect Portography in Transjugular Intrahepatic Portosystemic Shunt(TIPS)

PURPOSE: To determine the usefulness of carbon dioxide(CO2) indirect portography during TIPS procedure. MATERIALS AND METHODS: We evalvated eight patients who had undergone TIPS due to variceal hemorrhage or ascites caused by portal hypertension. All patients but one with complete situs inversus underwent wedged right hepatic venography for visualization of the portal vein using CO2. For CO2 indirect portal venography, 50cc of CO2 was injected by hand without prior injection of a small amount of CO2. In three patients a 5-F angiographic catheter was wedged into the right hepatic vein, and in the other five a 9-F sheath from a Ring 's transjugular access set was adjunctively wedged into the right hepatic vein over the 5-F catheter. The time required for portal vein puncture was defined as the time between the indirect portal venography procedure and the first procedure after successful portal vein puncture. RESULTS: All patients successfully underwent TIPS without any immediate complication. The portal vein was visualized by CO2 in 7 of 8 patients (87.5 %). Two of three patients who underwent indirect portography with only a 5-F catheter wedging demonstrated opacification of the right portal vein; in the remaining patient the portal venous system was not visualized. Of the five patients who underwent indirect portography with an adjunctive 9-F sheath wedged in the right hepatic vein, four showed opacification from the peripheral to the main portal vein, and in the other, the only right peripheral portal vein was opacified. The mean time for portal vein puncture was 20.5 minutes. CONCLUSION: For visualization of the portal venous system during TIPS procedure, the use of CO2 indirect portography is feasible.