Abstract

Transplanted stem cells can induce and enhance functional recovery in experimental stroke. Invasive analysis has been extensively used to provide detailed cellular and molecular characterization of the stroke pathology and engrafted stem cells. But post mortem analysis is not appropriate to reveal the time scale of the dynamic interplay between the cell graft, the ischemic lesion and the endogenous repair mechanisms. This review describes non-invasive imaging techniques which have been developed to provide complementary in vivo information. Recent advances were made in analyzing simultaneously different aspects of the cell graft (e.g., number of cells, viability state, and cell fate), the ischemic lesion (e.g., blood–brain-barrier consistency, hypoxic, and necrotic areas) and the neuronal and vascular network. We focus on optical methods, which permit simple animal preparation, repetitive experimental conditions, relatively medium-cost instrumentation and are performed under mild anesthesia, thus nearly under physiological conditions. A selection of recent examples of optical intrinsic imaging, fluorescence imaging and bioluminescence imaging to characterize the stroke pathology and engrafted stem cells are discussed. Special attention is paid to novel optimal reporter genes/probes for genetic labeling and tracking of stem cells and appropriate transgenic animal models. Requirements, advantages and limitations of these imaging platforms are critically discussed and placed into the context of other non-invasive techniques, e.g., magnetic resonance imaging and positron emission tomography, which can be joined with optical imaging in multimodal approaches.

Highlights

  • The stroke pathology and regeneration processes induced by endogenous mechanisms or engrafted stem cells have been studied extensively

  • We review here optical imaging as one promising approach to shed new light on structural and functional components of stem cell therapy in stroke

  • We introduced fluorescence and bioluminescence imaging (FLI and BLI) which have been extensively developed in the last decade to meet the criteria of a highly sensitive and minimally invasive set-up (Figure 1)

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Summary

INTRODUCTION

The stroke pathology and regeneration processes induced by endogenous mechanisms or engrafted stem cells have been studied extensively. New neurons are found in the rat striatum after experimental stroke (Arvidsson et al, 2002), but neurogenesis and functional neuronal integration seem alone not to be able to restore brain function In this line, exogenous stem cells, e.g., neural stem cells (NSCs) derived from embryonic or inducedpluripotent stem cells, have been implanted in experimental rodent models of stroke and found to increase functional recovery in many studies (Bliss et al, 2007; Oki et al, 2012). Based on the first non-invasive experiments with superficial sources, optical neuroimaging has been so far most effectively implemented for brain tumor studies (Massoud et al, 2008b) and less for neurological disease models or endogenous/exogenous NSCs in which sensitivity is essential.

Optical neuroimaging in stroke therapy
Findings
FUTURE DIRECTIONS
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