title: Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.
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.
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Riegler
authors.affiliation: 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.
authors.forename: Antje
authors.initials: A
authors.lastname: Ebert
authors.affiliation: 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.
authors.forename: Xulei
authors.initials: X
authors.lastname: Qin
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Mouer
authors.initials: M
authors.lastname: Wang
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ameen
authors.affiliation: 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.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kodo
authors.affiliation: 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.
authors.forename: Sang-Ging
authors.initials: SG
authors.lastname: Ong
authors.affiliation: 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.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Evgenios
authors.initials: E
authors.lastname: Neofytou
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Gold
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Connolly
authors.affiliation: 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.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005682:Gadolinium; D006321:Heart / Q000503:physiopathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D016086:Lentivirus / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000637:transplantation; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000473:pathology*; D011923:Rats, Nude; D013724:Teratoma / Q000097:blood* / Q000098:blood supply / Q000175:diagnosis*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D005682:Gadolinium
keywords: magnetic resonance imaging; microRNA biomarker; pluripotent stem cells; serum biomarker; tumorigenicity; ultrasound imaging