Skip to main content

Molecular imaging for stem cell therapy in the brain


Molecular 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 & 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.


Current neuroimaging techniques give very limited insight into molecular and cellular sequences of events. Therefore, the exact underlying mechanism by which neural stem cells target physiological or pathological brain areas remains elusive. Monitoring of these cells is currently also carried out by the use of various modes of molecular imaging, which is a (novel) technology for visualizing metabolism and signal transduction to gene expression. Most importantly, molecular imaging will render possible the identification of potential therapeutic targets in the development of new treatment strategies and in their successful implementation in clinical application.


In such a context, Micci et al. [1] have demonstrated the human sodium iodide symporter (hNIS), a transmembrane glycoprotein and widely used probe, as a new transporter-based reporter gene for non-invasive molecular imaging and point out one of the principal challenges of molecular imaging of the brain [26]. Such new reporter genes will help find the best target on a neurochemical as well as on a commercial level as applying 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 both cellular and molecular levels.

Molecular imaging of stem cells has two principal advantages over other methods [611]: it allows visual representation, characterization, and quantification of biological processes in the same live recipient over time and it is non-invasive. In this context, hNIS may be an alternative to already-existing vectors like HSV-1 TK or D2R. As hNIS neither is physiologically expressed in the brain nor crosses the intact blood–brain barrier, we can directly examine how it relates to enzymatic activity or gene expression, being perhaps essential to obtain a more detailed description of the failure or success of the cell therapy. Therefore, hNIS incorporated into vectors will make it possible to more fully understand with a relatively high sensitivity the function of protein networks and their role in the spread of stem cells. Such knowledge will facilitate the discovery of still more informative biomarkers.

This restriction leads us to the question of which vector probes should be ideal for molecular imaging of cell therapy. Unfortunately, we think that it is easier to answer this question in different ways. A new vector probe should be able to help to answer some of the ongoing questions in stem cell therapy: the most efficacious route of delivery, the appropriate choice of stem cell type(s), the optimal cell population for treatment in a chronic setting, and the favorable time-point of cell delivery. A safe, non-invasive, and repeatable imaging modality that could identify injected stem cells would be able to answer questions about cell viability and retention as well as provide the ability to adjust the assessment of bioactivity on the basis of actual delivered doses of cells [7, 8]. In the long term, stem cell-derived regeneration still faces difficulties in its efforts to improve because of the need to monitor stem cells continuously with high temporal resolution and good biocompatibility. Under such circumstances, the properties of differentiation and self-renewal of stem cells over long periods of time might be of importance. Moreover, multimodality imaging reporter genes will allow us to choose the imaging technologies that are most appropriate for the biologic problem at hand and facilitate the clinical application of reporter gene technologies.

The investigation by Micci et al. [1] is in line with these current questions of stem cell research, but we have to be aware that stem cell therapy can be used for the clinical daily practice only if safety and efficacy of the transplanted cells can be guaranteed. However, inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials [79]. Therefore, there is a need to refine and optimize tracking techniques, as is done by Micci et al. [1]. Moreover, instrumentational improvements, the identification of novel targets and genes, and imaging probe developments suggest that molecular-genetic imaging is likely to play an increasingly important role in the diagnosis and therapy of some brain diseases [1114]. Fortunately, the advent of molecular imaging will continue to lead unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, bio-distribution, immunogenicity, and tumorogenicity, in the targeted tissues of interest.


Molecular imaging opens a new door to stem cell therapy, not only in treatment monitoring but also in better understanding the underlying (molecular) processes. Tracking techniques are an important part of this imaging progress and underline the important impact of molecular imaging on patient management with stem cell therapy of the brain.



human sodium iodide symporter


  1. 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. Stem Cell Res Ther. 2015;6:131.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Spiriev T, Sandu N, Schaller B. Molecular imaging and tracking stem cells in neurosciences. Methods Mol Biol. 2013;1052:195–201.

    Article  CAS  PubMed  Google Scholar 

  3. Sandu N, Spiriev T, Schaller B. Stem cell transplantation in neuroscience: the role of molecular imaging. Stem Cell Rev. 2012;8:1265–6.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Sandu N, Momen-Heravi F, Sadr-Eshkevari P, Schaller B. Molecular imaging for stem cell transplantation in neuroregenerative medicine. Neurodegener Dis. 2012;9:60–7.

    Article  CAS  PubMed  Google Scholar 

  6. Sandu N, Pöpperl G, Toubert ME, Spiriev T, Arasho B, Orabi M, et al. Current molecular imaging of spinal tumors in clinical practice. Mol Med. 2011;17:308–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Sandu N, Schaller B. Stem cell transplantation in brain tumors: a new field for molecular imaging? Mol Med. 2010;16:433–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Schaller BJ, Cornelius JF, Sandu N, Buchfelder M. Molecular imaging of brain tumors personal experience and review of the literature. Curr Mol Med. 2008;8:711–26.

    Article  CAS  PubMed  Google Scholar 

  9. Schaller B, Cornelius JF, Sandu N. Molecular medicine successes in neuroscience. Mol Med. 2008;14:361–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Schaller BJ. Strategies for molecular imaging dementia and neurodegenerative diseases. Neuropsychiatr Dis Treat. 2008;4:585–612.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Schaller BJ, Modo M, Buchfelder M. Molecular imaging of brain tumors: a bridge between clinical and molecular medicine? Mol Imaging Biol. 2007;9:60–71.

    Article  CAS  PubMed  Google Scholar 

  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.

    Google Scholar 

  13. Sandu N, Pöpperl G, Toubert ME, Arasho B, Spiriev T, Orabi M, et al. Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report. J Med Case Rep. 2011;5:522.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Schaller B. Influences of brain tumor-associated pH changes and hypoxia on epileptogenesis. Acta Neurol Scand. 2005;111:75–83.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Bernhard Schaller.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

NS, TC, and BS drafted the manuscript. All authors read and approved the final manuscript.

See related research by Micci et al.,

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sandu, N., Chowdhury, T. & Schaller, B. Molecular imaging for stem cell therapy in the brain. Stem Cell Res Ther 6, 252 (2015).

Download citation

  • Published:

  • DOI: