Small molecules for selective elimination of contaminating pluripotent stem cells from cultures of their differentiated derivatives
A German university offers a new method for selective chemical ablation of undifferentiated cells in pluripotent stem cell-derived populations. It works with small molecules that are toxic against pluripotent stem cells but not toxic to differentiated cells of interest. Applications are in cardiac regenerative medicine. In vitro results are available. Industrial licensees are sought.
The university offers access to rights for commercial use as well as the opportunity for further co-development within a license agreement to companies from the pharmaceutical and medical sector.
The generation of cardiomyocytes (CMs) from pluripotent stem cells (PSCs) holds great promise for cardiac regenerative medicine. Of particular interest are CMs derived from induced pluripotent stem cells (iPSCs) because they can be obtained by converting autologous somatic cells into an early embryonic PSC-like state, thus circumventing ethical concerns related to the use of embryonic stem cells (ESCs). However, a fundamental obstacle in the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are contaminating undifferentiated PSCs that remain in the population of differentiated cells which carry the risk of tumour formation. This problem is due to an incomplete in vitro differentiation of PSCs to CMs. While genetic manipulations are effective in removal of contaminating PSCs they raise safety concerns. PSC ablation by immunologic targeting is safe but less efficient because single-cell dissociation is required. A German university now offers a most promising strategy: the selective chemical ablation of undifferentiated cells in PSC-derived populations using small molecules which are not toxic to differentiated cells of interest. The diamines of the general formula (see figure), particularly salicylic diamines, are capable of selectively eliminating PSCs from their differentiated derivatives. The diamines exhibit high cytotoxicity to murine and human PSCs but not to CMs derived from these. They are suitable for the elimination of PSCs from differentiating derivatives that contain CMs, either in unpurified or pre-purified form. First in vitro results with murine and human cells are available. The university offers licensing agreements to pharmaceutical industry. This would include further co-development.
Advantages and innovations
This invention presents a new route to cardiomyocytes. It distinguishes itself from other approaches by the fact that the compounds are toxic against PSCs but not against differentiated derivatives. The PSC-specific cytotoxic activity is furthermore significantly higher than in known small molecules. Advantages are that the compounds are readily available and that they can be used in tissue repair.
Under development/lab tested
Intellectual Property Rights (IPR)
Patent(s) applied for but not yet granted
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