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Selective Elimination of Human Pluripotent Stem Cells and Cancer Stem Cells

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

 

Category

Medical Sciences, Stem cells, Small molecules

Our Innovation

Improved removal of PSCs may be obtained by identifying small molecules that selectively perturb crucial pathways in PSCs, and thus induce cell death in these cells only.  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

Advantages

  • This method is more rapid, efficient, robust and scalable than any other method.
  • This method does not need genetic manipulation of the cells or dissociation into single cells. Thus, it allows genetically normal PSCs to be induced to differentiate into complex structures, which need not be disassembled prior to their transplantation.
  • Compounds which selectively target undifferentiated cells without affecting their differentiated derivatives, are capable of efficiently and robustly eliminating undifferentiating cancer cells.

Technology

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.

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

The Opportunity

Existing methods for removing potentially tumorigenic residual pluripotent stem cells (PSCs) from differentiated cultures are based on either genetic manipulations or on cell sorting. Such processes are generally not suitable for cell therapy purposes. There is therefore a need for a robust method for the elimination of undifferentiated pluripotent stem cells from culture, particularly a method which is suitable for cell therapy purposes. Human pluripotent stem cells (hPSCs) hold great promise for regenerative medicine, due to their unique abilities to self-renew and to differentiate into all the cell types of the human body.

Current Development Stage

TRL4 Technology validated in lab

Patent Status

Granted US 9,456,998; Japan (Asia) 6,293,127

Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
+972-2-6586608
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