In this work, we suggest a method, based on the data driven computational mechanics framework introduced by Kirchdoerfer and Ortiz, to extract representative strain-stress couples from a collection of non-homogenous full field measurements corresponding to different loading conditions

Coret, Michel

Leygue, Adrien

Réthoré, Julien

Stainier, Laurent

Verron, Erwan

Nora Sandu

Tumul Chowdhury

Bernhard Schaller

MUCC (Crossref)

Molecular imaging for stem cell therapy in the brain

AbstractMolecular imaging is one of the methods to follow-up stem cell therapy by visualization in the brain. In a recent article in Stem Cell Research &amp; Therapy, Micci et al. offer a thorough discussion of the advantages and disadvantages of this method and their roles in the future. The authors are among the very first who have implemented recently introduced molecular imaging techniques in experimental research and clinical practice.</jats:p

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Sandu et al. Stem Cell Research & Therapy  (2015) 6:252 DOI 10.1186/s13287-015-0242-7COMMENTARY Open AccessMolecular imaging for stem cell therapy inthe brainNora Sandu1,2, Tumul Chowdhury3 and Bernhard Schaller1,2*See related research by Micci et al., http://www.stemcellres.com/content/6/1/131AbstractMolecular imaging is one of the methods to follow-upstem cell therapy by visualization in the brain. In arecent article in Stem Cell Research & Therapy, Micciet al. offer a thorough discussion of the advantagesand disadvantages of this method and their roles inthe future. The authors are among the very first whohave implemented recently introduced molecularimaging techniques in experimental research andclinical practice.D2R. As hNIS neither is physiologically expressed inBackgroundCurrent neuroimaging techniques give very limited insightinto molecular and cellular sequences of events. There-fore, the exact underlying mechanism by which neuralstem cells target physiological or pathological brain areasremains elusive. Monitoring of these cells is currently alsocarried out by the use of various modes of molecular im-aging, which is a (novel) technology for visualizing metab-olism and signal transduction to gene expression. Mostimportantly, molecular imaging will render possible theidentification of potential therapeutic targets in the devel-opment of new treatment strategies and in their successfulimplementation in clinical application.DiscussionIn such a context, Micci et al. [1] have demonstratedthe human sodium iodide symporter (hNIS), a trans-membrane glycoprotein and widely used probe, as anew transporter-based reporter gene for non-invasivemolecular imaging and point out one of the principalchallenges of molecular imaging of the brain [2–6].Such new reporter genes will help find the best target* Correspondence: bernhardjschaller@gmail.com1University of Oxford, Wellington Square, Oxford OX1 2JD, UK2University of Southampton, University Road, Southampton SO17 1BJ, UKFull list of author information is available at the end of the article© 2015 Sandu et al. Open Access This articleInternational License (http://creativecommonsreproduction in any medium, provided you gthe Creative Commons license, and indicate if(http://creativecommons.org/publicdomain/zeon a neurochemical as well as on a commercial level asapplying stem cell transplantation in a clinical medium,which is necessity for analysis of the benefit to detect,localize, and examine the stem cells in vivo at bothcellular and molecular levels.Molecular imaging of stem cells has two principaladvantages over other methods [6–11]: it allows visualrepresentation, characterization, and quantification ofbiological processes in the same live recipient over timeand it is non-invasive. In this context, hNIS may be analternative to already-existing vectors like HSV-1 TK orthe brain nor crosses the intact blood–brain barrier, wecan directly examine how it relates to enzymatic activ-ity or gene expression, being perhaps essential to obtaina more detailed description of the failure or success ofthe cell therapy. Therefore, hNIS incorporated into vec-tors will make it possible to more fully understand witha relatively high sensitivity the function of protein net-works and their role in the spread of stem cells. Suchknowledge will facilitate the discovery of still more in-formative biomarkers.This restriction leads us to the question of which vectorprobes should be ideal for molecular imaging of cell ther-apy. Unfortunately, we think that it is easier to answer thisquestion in different ways. A new vector probe should beable to help to answer some of the ongoing questions instem cell therapy: the most efficacious route of delivery,the appropriate choice of stem cell type(s), the optimal cellpopulation for treatment in a chronic setting, and thefavorable time-point of cell delivery. A safe, non-invasive,and repeatable imaging modality that could identifyinjected stem cells would be able to answer questionsabout cell viability and retention as well as provide theability to adjust the assessment of bioactivity on thebasis of actual delivered doses of cells [7, 8]. In thelong term, stem cell-derived regeneration still facesdifficulties in its efforts to improve because of theneed to monitor stem cells continuously with highis distributed under the terms of the Creative Commons Attribution 4.0.org/licenses/by/4.0/), which permits unrestricted use, distribution, andive appropriate credit to the original author(s) and the source, provide a link tochanges were made. The Creative Commons Public Domain Dedication waiverro/1.0/) applies to the data made available in this article, unless otherwise stated.Sandu et al. Stem Cell Research & Therapy  (2015) 6:252 Page 2 of 2temporal resolution and good biocompatibility. Undersuch circumstances, the properties of differentiation andself-renewal of stem cells over long periods of time mightbe of importance. Moreover, multimodality imaging re-porter genes will allow us to choose the imaging technolo-gies that are most appropriate for the biologic problem athand and facilitate the clinical application of reporter genetechnologies.The investigation by Micci et al. [1] is in line with thesecurrent questions of stem cell research, but we have to beaware that stem cell therapy can be used for the clinicaldaily practice only if safety and efficacy of the transplantedcells can be guaranteed. However, inefficient stem celldifferentiation, difficulty in verifying successful delivery tothe target organ, and problems with engraftment allhamper the transition from laboratory animal studies tohuman clinical trials [7–9]. Therefore, there is a need torefine and optimize tracking techniques, as is done byMicci et al. [1]. Moreover, instrumentational improve-ments, the identification of novel targets and genes, andimaging probe developments suggest that molecular-genetic imaging is likely to play an increasingly importantrole in the diagnosis and therapy of some brain diseases[11–14]. Fortunately, the advent of molecular imaging willcontinue to lead unprecedented progress in understandingthe fundamental behavior of stem cells, including theirsurvival, bio-distribution, immunogenicity, and tumoro-genicity, in the targeted tissues of interest.ConclusionsMolecular imaging opens a new door to stem cell therapy,not only in treatment monitoring but also in better under-standing the underlying (molecular) processes. Trackingtechniques are an important part of this imaging progressand underline the important impact of molecular imagingon patient management with stem cell therapy of the brain.AbbreviationhNIS: human sodium iodide symporter.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsNS, TC, and BS drafted the manuscript. All authors read and approved thefinal manuscript.Author details1University of Oxford, Wellington Square, Oxford OX1 2JD, UK. 2University ofSouthampton, University Road, Southampton SO17 1BJ, UK. 3Department ofAnesthesiology and Peri-operative Medicine, University of Manitoba,Winnipeg, MB R3T 2N2, Canada.References1. Micci M-A, Boone DR, Parsley MA, Wei J, Patrikeev I, Motamedi M, et al.Development of a novel imaging system for cell therapy in the brain. StemCell Res Ther. 2015;6:131.2. Spiriev T, Sandu N, Schaller B. Molecular imaging and tracking stem cells inneurosciences. Methods Mol Biol. 2013;1052:195–201.3. Sandu N, Spiriev T, Schaller B. Stem cell transplantation in neuroscience: therole of molecular imaging. Stem Cell Rev. 2012;8:1265–6.4. Sandu N, Schaller B. Molecular imaging of stem cell therapy in brain tumors:a step towards personalized medicine. Arch Med Sci. 2012;8:601–5.5. Sandu N, Momen-Heravi F, Sadr-Eshkevari P, Schaller B. Molecular imagingfor stem cell transplantation in neuroregenerative medicine. NeurodegenerDis. 2012;9:60–7.6. Sandu N, Pöpperl G, Toubert ME, Spiriev T, Arasho B, Orabi M, et al. Currentmolecular imaging of spinal tumors in clinical practice. Mol Med.2011;17:308–16.7. Sandu N, Schaller B. Stem cell transplantation in brain tumors: a new fieldfor molecular imaging? Mol Med. 2010;16:433–7.8. Schaller BJ, Cornelius JF, Sandu N, Buchfelder M. Molecular imaging of braintumors personal experience and review of the literature. Curr Mol Med.2008;8:711–26.9. Schaller B, Cornelius JF, Sandu N. Molecular medicine successes inneuroscience. Mol Med. 2008;14:361–64.10. Schaller BJ. Strategies for molecular imaging dementia andneurodegenerative diseases. Neuropsychiatr Dis Treat. 2008;4:585–612.11. Schaller BJ, Modo M, Buchfelder M. Molecular imaging of brain tumors: abridge between clinical and molecular medicine? Mol Imaging Biol.2007;9:60–71.12. Sandu N, Momen-Heravi F, Sadr-Eshkevari P, Arvantaj A, Schaller B.Molecular imaging of stem cells: a new area for neuroscience. In: Schaller B,editor. Molecular imaging. Rijeka, Croatia: InTech; 2012. p. 211–20.13. Sandu N, Pöpperl G, Toubert ME, Arasho B, Spiriev T, Orabi M, et al.Molecular imaging of potential bone metastasis from differentiated thyroidcancer: a case report. J Med Case Rep. 2011;5:522.14. Schaller B. Influences of brain tumor-associated pH changes and hypoxia onepileptogenesis. Acta Neurol Scand. 2005;111:75–83.

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Molecular imaging for stem cell therapy in the brain

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