Optical Imaging for Stem Cell Differentiation to Neuronal Lineage
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REVIEW
Optical Imaging for Stem Cell Differentiation to Neuronal Lineage Do Won Hwang & Dong Soo Lee
Received: 12 August 2011 / Revised: 22 November 2011 / Accepted: 24 November 2011 / Published online: 4 January 2012 # Korean Society of Nuclear Medicine 2011
Abstract In regenerative medicine, the prospect of stem cell therapy holds great promise for the recovery of injured tissues and effective treatment of intractable diseases. Tracking stem cell fate provides critical information to understand and evaluate the success of stem cell therapy. The recent emergence of in vivo noninvasive molecular imaging has enabled assessment of the behavior of grafted stem cells in living subjects. In this review, we provide an overview of current optical imaging strategies based on cell- or tissuespecific reporter gene expression and of in vivo methods to monitor stem cell differentiation into neuronal lineages. These methods use optical reporters either regulated by neuron-specific promoters or containing neuron-specific microRNA binding sites. Both systems revealed dramatic changes in optical reporter imaging signals in cells differentiating into a neuronal lineage. The detection limit of weak promoters or reporter genes can be greatly enhanced by adopting a yeast GAL4 amplification system or an engineering-enhanced luciferase reporter gene. Furthermore, we propose an advanced imaging system to monitor D. W. Hwang : D. S. Lee (*) Department of Nuclear Medicine, College of Medicine, Seoul National University, 28 Yongon-Dong, Jongno-Gu, Seoul 110-744, Korea e-mail: [email protected] D. W. Hwang Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea D. S. Lee WCU, Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
neuronal differentiation during neurogenesis that uses in vivo multiplexed imaging techniques capable of detecting several targets simultaneously. Keywords Reporter-based cell tracking . Differentiation imaging . Neuronal differentiation . Neuronal microRNA . Multiplex imaging
Introduction Over the last decade, stem cell therapy has been intensively studied in regenerative medicine to make possible the replacement of lost tissues with fresh tissue for functional recovery [1–3]. Amid numerous trials involving the therapeutic use of pluripotent stem cells, a number of techniques to elucidate the behavior of transplanted stem cells were developed for potential clinical use. Recently, the rapid progress of molecular imaging techniques has enabled noninvasive evaluation of the characteristics of transplanted stem cells and, in particular, of their viability. Molecular imaging allows real-time visualization of survival and quantitative viability measurements of stem cells implanted into an injured site by using stem cells labeled with proper radiotracers or reporter-based gene expression schemes [4–9]. However, to be successful with stem cell therapy, we should note that th
