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SMECS - Small molecules for selective elimination of contaminating pluripotent stem cells from cultures of their differentiated derivatives

Prof. Albrecht Berkessel, University of Cologne, Department of Chemistry; Dr Tomo Saric, University Hospital Cologne, Medical Faculty; Karsten Burkert, University Hospital Cologne, Medical Faculty; Prof. J├╝rgen Hescheler, University Hospital Cologne, Medical Faculty



The generation of cardiomyocytes from pluripotent stem cells (PSCs) holds great promise in cardiac cell therapies. Of particular interest is the generation of induced pluripotent stem cells (iPSCs) by reprogramming fibroblasts to stem-like cells, thus evading ethical concerns in view of embryonic stem cells (ESCs). However, a fundamental obstacle in the use of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) is the risk of undifferentiated pluripotent stem cells that remain in the population of differentiated cells forming tumours. This problem is due to an incomplete in vitro differentiation from pluripotent stem cells to cardiomyocytes.

Various strategies have been developed for the elimination of pluripotent stem cells utilizing transgenic, immunologic and chemical approaches as well as biophysical techniques. While genetic manipulations are effective but raise safety concerns, pluripotent stem cell ablation by immunologic targeting is safe but less efficient because single-cell dissociation is required.

In this regard, the most promising strategy is the chemical ablation of undifferentiated cells in pluripotent stem cell-derived populations using small molecules such as toxins.


The problem is solved by a method of eliminating the number or percentage of pluripotent stem cells or of enriching differentiating or differentiated cells in a cell population.

The diamines of the general formula (see figure), particularly salicylic diamines, are capable of selectively eliminating pluripotent stem cells from their differentiated derivatives. The diamines exhibited high cytotoxicity to murine and human pluripotent stem cells but not to cardiomyocytes derived from these.

They are usable for the elimination of pluripotent stem cells from differentiating derivatives of pluripotent stem cells that contain cardiomyocytes, either in unpurified or pre-purified form.

A further advantage of the diamines is that the compounds are readily available and show significantly higher pluripotent stem cell-specific cytotoxic activity in comparison to known small molecules.

Commercial Opportunity

On behalf of University of Cologne, PROvendis offers access to rights for commercial use as well as the opportunity for further co-development.

Development Status

First in vitro results of murine and human cells are available.

Patent Situation

A European patent application has been filed recently. Worldwide patent protection is possible.

Further Reading



SMECS - Small molecules for selective elimination of contaminating pluripotent stem cells from cultures of their differentiated derivatives

Generation of pure cardiomyocytes (CMs) by effective iPSC elimination upon treatment with small molecule agents (SM)