Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model.

Abstract

The growing number of victims of "stem cell tourism," the unregulated transplantation of stem cells worldwide, has raised concerns about the safety of stem cell transplantation. Although the transplantation of differentiated rather than undifferentiated cells is common practice, teratomas can still arise from the presence of residual undifferentiated stem cells at the time of transplant or from spontaneous mutations in differentiated cells. Because stem cell therapies are often delivered into anatomically sensitive sites, even small tumors can be clinically devastating, resulting in blindness, paralysis, cognitive abnormalities, and cardiovascular dysfunction. Surgical access to these sites may also be limited, leaving patients with few therapeutic options. Controlling stem cell misbehavior is, therefore, critical for the clinical translation of stem cell therapy. External beam radiation offers an effective means of delivering targeted therapy to decrease the teratoma burden while minimizing injury to surrounding organs. Additionally, this method avoids genetic manipulation or viral transduction of stem cells-which are associated with additional clinical safety and efficacy concerns. Here, we describe a protocol to create pluripotent stem cell-derived teratomas in mice and to apply external beam radiation therapy to selectively ablate these tumors in vivo.

• Authors: Karim Sallam, June-Wha Rhee, Tony Chour, Jessica D'addabbo, Andrew S Lee, Edward Graves, Patricia K Nguyen
• Journal: Journal of visualized experiments : JoVE (J Vis Exp) Issue 144 (02 17 2019) ISSN: 1940-087X [Electronic] United States
• PMID: 30829317 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Video-Audio Media)

Topics

• Animals
• Disease Models, Animal
• Humans
• Mice
• Pluripotent Stem Cells (pathology)
• Radiotherapy (methods)
• Teratoma (pathology, radiotherapy)
• Treatment Outcome