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Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

Loewenbrück, Kai F. and Fuchs, Beate and Hermann, Andreas and Brandt, Moritz and Werner, Annett and Kirsch, Matthias and Schwarz, Sigrid and Schwarz, Johannes and Schiller, Jürgen and Storch, Alexander (2011) Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State? Rejuvenation Resarch, 14 (4). pp. 371-381. ISSN 1549-1684. https://resolver.caltech.edu/CaltechAUTHORS:20110908-091401456

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Abstract

Recently, a peak at 1.28 ppm in proton magnetic resonance spectroscopy (^1H-MRS) of neural stem cells (NSCs) was introduced as a noninterventional biomarker for neurogenesis in vivo. This would be an urgently needed requisite for translational studies in humans regarding the beneficial role of adult neurogenesis for the structural and functional integrity of the brain. However, many concerns have risen about the validity of the proposed signal as a specific marker for NSCs. The peak has also been related to cell-type-independent phenomena such as apoptosis or necrosis. Thus, we compared the 1.28-ppm peak in various immature stem cell populations, including embryonic stem cells, mouse embryonic fibroblasts, embryonic stem cell– and induced pluripotent stem cell–derived NSCs, ex vivo isolated embryonic NSCs, as well as mature and tumor cell types from different germ layers. To correlate the integral peak intensity with cell death, we induced both apoptosis with camptothecin and necrosis with sodium azide. A peak at 1.28 ppm was found in most cell types, and in most, but not all, NSCH cultures, demonstrating no specificity for NSCs. The intensities of the 1.28-ppm resonance significantly correlated with the rate of apoptosis, but not with the rate of necrosis, cell cycle phase distribution, cell size, or type. Multiple regression analysis displayed a significant predictive value of the peak intensity for apoptosis only. In this context, its specificity for apoptosis as a major selection process during neurogenesis may suggest this resonance as an indirect marker for neurogenesis in vivo.


Item Type:Article
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http://dx.doi.org/10.1089/rej.2010.1102DOIUNSPECIFIED
http://www.liebertonline.com/doi/abs/10.1089/rej.2010.1102PublisherUNSPECIFIED
Additional Information:© 2011 Mary Ann Liebert, Inc. Received: August 15, 2010. Accepted February 15, 2011. Online Ahead of Print: May 6, 2011. The authors express their grateful thanks to Eberhard Kuhlisch, Dresden University of Technology, for help in statistics, Claudia Waskow, Center for Regenerative Therapies Dresden, for methodological cell culture advice, and Oliver Speck, Otto von Guericke-Universität Magdeburg, for help with high-field 1H-MRS. Induced pluripotent stem cells were kindly provided by Hans R. Schöler, Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany. The authors would like to thank Susann Höfner, Sylvia Kanzler, Andrea Kempe, and Cornelia May for excellent technical assistance. The work was supported in part by the Medical Faculty Research Program MeDDrive to A.H. and M.B., and by the Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research Center 655: Cells into tissues: stem cell and progenitor commitment and interactions during tissue formation" (SFB 655 Dresden, project A23) to A.S., and the DFG-Research Center for Regenerative Therapies Dresden (CRTD) to K.L., A.H., M.B., and A.S. Author Contributions: Kai F. Lowenbrück: Conception and design, collection and/or assembly of data, co-principal investigator and grant support, data analysis and interpretation, writing and revision of manuscript. Beate Fuchs: Design, collection and/or assembly of data, data analysis and interpretation, manuscript writing. Andreas Hermann: Conception and design, provision of study material, collection and/or assembly of data, data analysis and interpretation, manuscript writing. Moritz Brandt: Collection and/or assembly of data, data analysis and interpretation, revising of manuscript. Annett Werner: Collection and/or assembly of data, data analysis and interpretation, revising of manuscript. Sigrid Schwarz: Collection and/or assembly of data, revising of manuscript. Matthias Kirsch: Provision of study material. Johannes Schwarz: Collection and/or assembly of data, revising of manuscript. Jürgen Schiller: Conception and design, coprincipal investigator, data analysis and interpretation, manuscript writing. Alexander Storch: Conception and design, co-principal investigator and grant support, data analysis and interpretation, writing, and revision of manuscript.
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Funding AgencyGrant Number
Medical Faculty Research Program MeDDriveUNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG) Collaborative Research CenterSFB 655 Dresden
Issue or Number:4
Record Number:CaltechAUTHORS:20110908-091401456
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110908-091401456
Official Citation:Kai F. Loewenbrück, Beate Fuchs, Andreas Hermann, Moritz Brandt, Annett Werner, Matthias Kirsch, Sigrid Schwarz, Johannes Schwarz, Jürgen Schiller and Alexander Storch. Rejuvenation Research. August 2011, 14(4): 371-381. doi:10.1089/rej.2010.1102.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:25252
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:08 Sep 2011 16:42
Last Modified:03 Oct 2019 03:04

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