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Stem Cell Reports. 2016 Feb 9;6(2):176-87. doi: 10.1016/j.stemcr.2015.12.008. Epub 2016 Jan 14.

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

Author information

1
Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA; Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
3
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA; Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Molecular Imaging Program, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.

Abstract

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 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) 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.

KEYWORDS:

magnetic resonance imaging; microRNA biomarker; pluripotent stem cells; serum biomarker; tumorigenicity; ultrasound imaging

PMID:
26777057
PMCID:
PMC4750097
DOI:
10.1016/j.stemcr.2015.12.008
[Indexed for MEDLINE]
Free PMC Article

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