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

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. H...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2016-02-01
Series:Stem Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671115003732
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author 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
author_facet 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
author_sort Johannes Riegler
collection DOAJ
description 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.
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spelling doaj.art-a0b756cf3908414a863e8f913bab1d552022-12-21T18:10:29ZengElsevierStem Cell Reports2213-67112016-02-016217618710.1016/j.stemcr.2015.12.008Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived TeratomasJohannes Riegler0Antje Ebert1Xulei Qin2Qi Shen3Mouer Wang4Mohamed Ameen5Kazuki Kodo6Sang-Ging Ong7Won Hee Lee8Grace Lee9Evgenios Neofytou10Joseph D. Gold11Andrew J. Connolly12Joseph C. Wu13Stanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USADepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Lorry Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2213671115003732magnetic resonance imagingultrasound imagingserum biomarkermicroRNA biomarkerpluripotent stem cellstumorigenicity
spellingShingle 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
Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
Stem Cell Reports
magnetic resonance imaging
ultrasound imaging
serum biomarker
microRNA biomarker
pluripotent stem cells
tumorigenicity
title Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
title_full Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
title_fullStr Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
title_full_unstemmed Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
title_short Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
title_sort comparison of magnetic resonance imaging and serum biomarkers for detection of human pluripotent stem cell derived teratomas
topic magnetic resonance imaging
ultrasound imaging
serum biomarker
microRNA biomarker
pluripotent stem cells
tumorigenicity
url http://www.sciencedirect.com/science/article/pii/S2213671115003732
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