Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas

Johannes Riegler; Antje Ebert; Xulei Qin; Qi Shen; Mouer Wang; Mohamed Ameen; Kazuki Kodo; Sang-Ging Ong; Won Hee Lee; Grace Lee; Evgenios Neofytou; Joseph D. Gold; Andrew J. Connolly; Joseph C. Wu

doi:10.1016/j.stemcr.2015.12.008

Stem Cell Reports (Feb 2016)

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas

Johannes Riegler,
Antje Ebert,
Xulei Qin,
Qi Shen,
Mouer Wang,
Mohamed Ameen,
Kazuki Kodo,
Sang-Ging Ong,
Won Hee Lee,
Grace Lee,
Evgenios Neofytou,
Joseph D. Gold,
Andrew J. Connolly,
Joseph C. Wu

Affiliations

Johannes Riegler: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Antje Ebert: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Xulei Qin: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Qi Shen: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Mouer Wang: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Mohamed Ameen: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Kazuki Kodo: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Sang-Ging Ong: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Won Hee Lee: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Grace Lee: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Evgenios Neofytou: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Joseph D. Gold: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA
Andrew J. Connolly: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
Joseph C. Wu: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA

DOI: https://doi.org/10.1016/j.stemcr.2015.12.008
Journal volume & issue: Vol. 6, no. 2
pp. 176 – 187

Abstract

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The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm3. A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm3 and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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