Factors Inducing Pluripotent Stem Cells differentiation towards pancreatic beta cells

Benvenisty Nissim, HUJI, Faculty of Science, The Alexander Silberman Institute for Life Sciences


The pluripotent cell-specific inhibitor (PluriSIns) family selectively targets human pluripotent stem cells (hPSCs), and efficiently and robustly eliminates all undifferentiated cells in culture, without affecting their differentiated derivatives. Application of these small molecules to cultures of differentiated cells prior to their transplantation into patients, would considerably decrease, and even eliminate the risk of tumor formation due to residual undifferentiated cells

  • Large range of doses of PluriSIn#1 are effective in eliminating tumorigenic undifferentiated human pluripotent stem cells.
  • Developed capability to achieve concentrations of over 100 μM, which gives a large therapeutic range

Our Innovation

  • Assessment of PluriSIn#1 effects on tumor formation


Left: Control teratoma injected only with DMSO. Right: Teratoma injected with PluriSIn#1. Short arrowheads show the site of injection labeled with India Ink. The arrows, in the left inset, show foci of tumorigenic undifferentiated cells positive for Nanog (these cells are missing in the right inset, demonstrating the effect of treatment of PluriSIn#1).



The pharmacological approach is based on targeting the cellular processes that are uniquely vital to PSCs. The inhibition of such processes would be expected to induce cell death specifically in the remaining contaminant PSCs during cell therapies. This approach is less costly than the genetic approach and the immunological approach and does not require single-cell dissociation prior to exposure to the drug. The PluriSIns uniquely target PCS and do not have any effect on the viability of the differentiated cell.

15 PluriSIns were first discovered from a pool of over 52,000 small molecules and were tested against a variety of cells from all three germ layers. PluriSIn#1 is an inhibitor of stearoyl-coA desaturase (SCD1), an enzyme which catalyzes production of oleic acid by desaturation of stearic acid.


Fig. 1: PluriSIn#1 mechanism of action (ER – endoplasmic reticulum)


Current Development Stage:

Phase I clinical trials in several countries running. The research relates to the use of human pluripotent stem cells (PSCs) in regenerative medicine


Patent Status

Granted US 9,394,523

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
Contact ME: