Optical Imaging for Stem Cell Differentiation to Neuronal Lineage

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 neuronal differentiation during neurogenesis that uses in vivo multiplexed imaging techniques capable of detecting several targets simultaneously.

An NIR‐II Fluorescence/Dual Bioluminescence Multiplexed Imaging for In Vivo Visualizing the Location, Survival, and Differentiation of Transplanted Stem Cells

“…During the process of bone regeneration, the transplanted stem cells and host cells may both contribute to the generation of new bone. Thus, understanding the therapeutic mechanisms and the interactions between transplanted cells and host cells is of fundamental importance for developing safe cell therapies, and will be needed to bring cell‐based therapies more broadly to the clinic . Therefore, a multichannel fluorescence microscope ranging from 400 to 1700 nm (Suzhou NIR‐Optics Technology Co., Ltd., China) was developed to enable the simultaneous collection of fluorescence signals both in the visible and the second near‐infrared windows.…”

“…Recently, live imaging studies using fluorescence imaging (FI), magnetic resonance imaging (MRI), or positron emission tomography (PET) imaging have provided ideal methodologies for investigations into the biodistribution, survival, function, and therapeutic effects of transplanted stem cells during the regeneration process. However, the in vivo fate and regenerative capabilities of transplanted stem cells are still far from being fully understood, partly due to the failure of simultaneously monitoring the three dynamic biological events of translocation, survival, and differentiation behaviors of transplanted stem cells in vivo.…”

Complementary early-phase magnetic particle imaging and late-phase positron emission tomography reporter imaging of mesenchymal stem cells in vivo

“…Other studies have assessed MSC in vivo differentiation with the use of well-characterized differentiation promoters with various reporter gene imaging techniques. [71][72][73] Moreover, evidence suggests that MSCs can also undergo malignant transformation, although the exact mechanism is still poorly understood. 43 In contrast, two mice did not show the rapid increase in BLI signal or PET uptake.…”