Zapping undifferentiated stem cells with light to prevent tumors

Stain, shine, kill
October 14, 2016

A light-activated dye turns on reactive oxygen species-mediated cell death in undifferentiated pluripotent stem cells, which could make stem cell therapies safer by preventing tumors. (credit: American Chemical Society)

Pluripotent stem cells (PSC) could be the key to a host of regeneration therapies because they can differentiate (develop) into basically any tissue type. But some PSCs in a culture dish can remain undifferentiated, and those could form teratomas — a type of tumor — if transplanted into patients.

Now a new light-based technology could remove this risk, Korean researchers report in an open-access paper in ACS Central Science.

Zapping undifferentiated PSCs

The researchers created a special dye (CDy1) that can selectively stain undifferentiated PSCs, but not differentiated ones. When the dye is exposed to light, it turns on the production of reactive oxygen species (ROS), which then kill these cells.

The researchers used undifferentiated PSCs transplanted into mice to demonstrate the method. None of the mice that received light-treated PSCs with the dye developed teratomas, whereas all of those in the control group (receiving PSCs that were not treated with light) did. The CDy1 and/or light irradiation did not negatively affect differentiated endothelial cells.

The researchers believe this dye-light combination could greatly improve the safety of a wide array of stem-cell therapies.

The researchers are affiliated with Sogang University, Republic of Korea Department of Medicine, Konkuk University, National University of Singapore, and Singapore Bioimaging Consortium (SBIC) Agency for Science, Technology and Research (A-STAR).

The work was supported by grants from the National Research Foundation of Korea and the Korea Health Industry Development Institute, and funded by the Korea government and A*STAR (Agency for Science, Technology and Research, Singapore) Biomedical Research Council and the Joint Council Office (JCO) Development Programme, A*STAR.

Abstract of Photodynamic Approach for Teratoma-Free Pluripotent Stem Cell Therapy Using CDy1 and Visible Light

Pluripotent stem cells (PSC) are promising resources for regeneration therapy, but teratoma formation is one of the critical problems for safe clinical application. After differentiation, the precise detection and subsequent elimination of undifferentiated PSC is essential for teratoma-free stem cell therapy, but a practical procedure is yet to be developed. CDy1, a PSC specific fluorescent probe, was investigated for the generation of reactive oxygen species (ROS) and demonstrated to induce selective death of PSC upon visible light irradiation. Importantly, the CDy1 and/or light irradiation did not negatively affect differentiated endothelial cells. The photodynamic treatment of PSC with CDy1 and visible light irradiation confirmed the inhibition of teratoma formation in mice, and suggests a promising new approach to safe PSC-based cell therapy.