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Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model
Published on: February 17, 2019
Photodynamic Approach for Teratoma-Free Pluripotent Stem Cell Therapy Using CDy1 and Visible Light
Seung-Ju Cho1, So-Yeon Kim2, Soon-Jung Park3
1Department of Life Sciences, Sogang University, 35 Baeckbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea; Research Institute for Basic Sciences, Sogang University, 35 Baeckbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.
Abstract:
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.
Insights
A novel fluorescent probe, CDy1, selectively eliminates undifferentiated pluripotent stem cells (PSCs) using visible light. This photodynamic approach prevents teratoma formation, paving the way for safer stem cell therapies.
Area of Science:
- Stem cell biology
- Regenerative medicine
- Photodynamic therapy
Background:
- Pluripotent stem cells (PSCs) hold great promise for regenerative therapies.
- Teratoma formation from residual undifferentiated PSCs is a major safety concern for clinical applications.
- Effective methods for detecting and eliminating undifferentiated PSCs post-differentiation are crucial but currently lacking.
Purpose of the Study:
- To investigate the potential of a novel PSC-specific fluorescent probe, CDy1, for eliminating undifferentiated PSCs.
- To evaluate the safety and efficacy of CDy1-mediated photodynamic therapy in preventing teratoma formation.
- To establish a practical procedure for ensuring teratoma-free stem cell therapy.
Main Methods:
- CDy1 probe was used to generate reactive oxygen species (ROS) selectively in PSCs.
- PSCs treated with CDy1 and visible light irradiation were assessed for viability.
- Differentiated endothelial cells were evaluated for any adverse effects from CDy1 and light.
- The efficacy of CDy1-mediated photodynamic treatment in inhibiting teratoma formation was tested in vivo in mice.
Main Results:
- CDy1 demonstrated selective induction of reactive oxygen species (ROS) in PSCs.
- Visible light irradiation of CDy1-treated PSCs resulted in selective cell death.
- Differentiated endothelial cells remained unaffected by CDy1 and light irradiation.
- Photodynamic treatment with CDy1 and light significantly inhibited teratoma formation in mice.
Conclusions:
- CDy1-mediated photodynamic therapy offers a selective method for eliminating undifferentiated PSCs.
- This approach effectively prevents teratoma formation, enhancing the safety of PSC-based therapies.
- CDy1 represents a promising tool for advancing the clinical application of stem cell therapy.
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