PluriSln 1

PluriSln 1 is an inhibitor of stearoyl-coA desaturase (SCD), and is a pluripotent cell-specific inhibitor.

Signaling Pathways >> Metabolic Enzyme/Protease >> Stearoyl-CoA Desaturase (SCD)

Research Areas >> Cancer

SCD[1]

PluriSln 1, a small-molecule inhibitor of stearoyl-coA desaturase (SCD), on induced pluripotent stem cells (iPS)-derived cardiomyocytes (CM). PluriSln 1 treatment significantly decreases the mRNA and protein level of Nanog, a marker for both cell pluripotency and tumor progression; importantly, we provide evidence that PluriSln 1 treatment at 20 µM for 1 day significantly induces the apoptosis of Nanog-positive iPS derivates (iPSD). In addition, PluriSln 1 treatment at 20 µM for 4 days diminished Nanog-positive stem cells in cultured iPSD while not increasing apoptosis of iPS-derived CM. To investigate whether PluriSln 1 treatment prevents tumorigenicity of iPSD after cell transplantation, we intramyocardially injected PluriSln 1- or DMSO-treated iPSD in a mouse model of myocardial infarction (MI). DMSO-treated iPSD readily formed Nanog-expressing tumors 2 weeks after injection, which is prevented by treatment with PluriSln 1. Moreover, treatment with PluriSln 1 does not change the expression of cTnI, α-MHC, or MLC-2v, markers of cardiac differentiation (P>0.05, n=4). Importantly, PluriSln 1-treated iPS-derived CM exhibits the ability to engraft and survive in the infarcted myocardium[1].

The differentiation of iPS cells to cardiomyocytes (CM) is induced by embryoid body (EB) formation. When iPS cells reached 70% confluency in 10-cm dishes, cells are digested using 0.25% trypsin/EDTA. Cell pellets are re-suspended in differentiation medium (DMEM with 20% FBS and 10 ng/mL BMP4) to a final concentration of 200,000 cells/mL. Cell suspensions are added to 6-well plates with Ulta-Low Attachment surfaces for 4 d to initiate EB formation. On day 5, EBs are cultured on 0.1% gelatin-coated dishes for 14 d using CF culture medium for the outgrowth of cardiac structures. At this stage, iPS cells undergoing EB formation are termed iPS derivates (iPSD)[1].

[1]. Zhang L, et al. Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: improving the safety of iPS cell transplantation to myocardium. Cell Cycle. 2014;13(5):762-71.

A939572 | SCD inhibitor 1 | CAY 10566 | MK-8245 | CVT-12012 | XEN723