Tracking Stem Cells for Cellular Therapy in Stroke

Abstract

Stem cell transplantation has emerged as a promising treatment strategy for stroke. The development of effective ways to monitor transplanted stem cells is essential to understand how stem cell transplantation enhances stroke recovery and ultimately will be an indispensable tool for advancing stem cell therapy to the clinic. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including optical imaging, magnetic resonance imaging (MRI), and positron emission tomography (PET), with emphasis on the benefits and drawbacks of each imaging approach. Key considerations such as the potential impact of each tracking system on stem cell function, as well as its relative applicability to humans are discussed. Finally, we describe multi-modal imaging strategies as a more comprehensive method to track transplanted stem cells in the stroke-injured brain.

Cell based therapies for ischemic stroke: From basic science to bedside

“…Bioluminescence imaging relies on the expression of a luminescent protein which is not endogenous to most mammalian cells, and thus requires transduction of the transplant cell population with a transgene encoding a luciferase enzyme. Following transplantation, cells expressing the luciferase enzyme can be visualized by systemic injection of the luciferase substrates, d -luciferin or coalenterazine (Manley and Steinberg, 2012). The simplicity of this approach, combined with its accuracy and ability to quantify signals, makes bioluminescence imaging attractive in terms of feasibility to track the migration (Andres et al, 2011a), biodistribution (Pendharkar et al, 2010), and survival (Rosenblum et al, 2012) of the grafted cells.…”

“…Immunostaining of SPIO-labeled grafts captured with confocal microscopy confirmed the MRI data over 2 months (Daadi et al, 2009; Guzman et al, 2007). Simultaneous and accurate representations of the grafts and the stroke were possible by rendering three dimensional reconstructions from the MR scans (Manley and Steinberg, 2012), allowing for direct comparison between stroke and graft sizes. Unfortunately, iron-rich glial cells and infiltrating macrophages that accumulate in the lesion boundary may also generate strong T2* contrast signals (Vandeputte et al, 2011), presenting a significant confound.…”

Viability, Differentiation Capacity, and Detectability of Super-Paramagnetic Iron Oxide-Labeled Muscle Precursor Cells for Magnetic-Resonance Imaging

“…While traditional histopathological techniques are too invasive to localize the injected cells in a clinical setting, cellular imaging approaches represent a noninvasive tool to follow implanted stem cells and to evaluate the success of the therapeutic treatment. 15,16 The most frequently employed techniques for cell tracking include magnetic resonance imaging (MRI), radioactive labeling for positron emission tomography and single photon emission computed tomography, bioluminescence, and fluorescence. For clinical application, MRI is considered a method of choice to track stem cells in vivo because of its high spatial resolution on soft tissue structures, therefore providing anatomical details of the graft area, which may also help in detecting inflammation or edema.…”

Experimental Models of Brain Ischemia: A Review of Techniques, Magnetic Resonance Imaging, and Investigational Cell-Based Therapies

“…While there is a wealth of literature on MRI-based cell tracking for monitoring reparative interventions in neurovascular and oncological disease, there are fundamental issues that remain open and need careful consideration (124, 125). Although existing studies demonstrate that short-term tagging under experimental conditions is feasible, we still have a rather constrained understanding of the effect of tagging on biological viability, of the exact bio-kinetics of the tagging molecules and of long-term tagging stability.…”