In vivo monitoring of cellular transplants by magnetic resonance imaging and positron emission tomography

Modo, Michel; Roberts, Toby J; Sandhu, Jasdeep K; Williams, Steve

doi:10.1517/14712598.4.2.145

Cited by 19 publications

(6 citation statements)

References 97 publications

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“…Clinical application of neonatal stem cell treatment will require noninvasive tracking of cells to (1) demonstrate accuracy of implantation; (2) monitor cell migration, proliferation, and location; and (3) assess structural tissue recovery or, conversely, adverse host reactions. Several reports have demonstrated that iron‐labeled NSCs can be tracked using magnetic resonance imaging (MRI)13–15 but did not use MR evaluation for long periods of time (>6 months) and did not correlate NSC behavior with the dynamics of underlying pathology—critical for the actual translation of NSC‐based therapeutics to patients 7, 11, 16, 17. The ability to monitor NSCs for extended periods is particularly important in newborns because long‐term implantation may pose unanticipated risks to the developing brain.…”

mentioning

confidence: 99%

Long‐term magnetic resonance imaging of stem cells in neonatal ischemic injury

Obenaus

Dilmac

Tone

et al. 2010

Annals of Neurology

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Objective Quantitative magnetic resonance imaging (MRI) can serially and non-invasively assess the degree of injury in rat pup models of hypoxic ischemic injury (HII). It can also non-invasively monitor stem cell migration following iron oxide pre-labeling. Reports have shown that neural stem cells (NSCs) may help mediate neuroprotection or stimulate neuroreparative responses in adult and neonatal models of ischemic injury. We investigated the ability of high-field MRI to monitor and non-invasively quantify the migration, proliferation, and location of iron oxide-labeled NSCs over very long time periods (58 weeks) in real time while contemporaneously correlating this activity with the evolving severity and extent of neural damage. Methods Labeled clonal murine NSCs were implanted 3 days after unilateral HII in 10 day old rat pups into the contralateral striatum or ventricle. We developed methods for objectively quantifying key aspects of dynamic NSC behavior (e.g., viability; extent and speed of migration; degree of proliferation; extent of integration into host parenchyma). MRI images were validated with histological and immunohistochemical assessments. Results mNSCs rapidly migrated (100μm/day) to the lesion site. Chains of migrating NSCs were observed in the corpus callosum. In pups subjected to HII, though not in intact control animals, we observed a 273% increase in the MR-derived volume of mNSCs 4 weeks after implantation (correlating with the known proliferative behavior of endogenous and exogenous NSCs) that slowly declined over the 58 week time course, with no adverse consequences. Large numbers of now quiescent mNSCs remained at the site of injury, many retaining their iron oxide label. Interpretation Our studies demonstrate that MRI can simultaneously monitor evolving neonatal cerebral injury as well as NSC migration and location. Most importantly, it can non-invasively monitor proliferation dynamically for prolonged time periods. To be able to pursue clinical trials in newborns using stem cell therapies, it is axiomatic that safety be insured through the long-term real time monitoring of cell fate and activity, particularly with regard to observing unanticipated risks to the developing brain. This study supports the feasibility of reliably using MRI for this purpose.

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confidence: 99%

Long‐term magnetic resonance imaging of stem cells in neonatal ischemic injury

Obenaus

Dilmac

Tone

et al. 2010

Annals of Neurology

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“…This is caused by mounting evidence that brain tumors may be caused by a single NSC that did not differentiate (22). The ability to monitor cell therapy in vivo is therefore desirable because it may provide more control over the activity of NSCs (23). One possibility is that stem cells will be engineered with a suicide gene (24) that could be activated if transplanted cells did not behave in a therapeutic manner.…”

Section: Stem Cell Transplantation In Brain Tumors: a New Field For Mmentioning

confidence: 99%

Stem Cell Transplantation in Brain Tumors: A New Field for Molecular Imaging?

Sandu

Schaller

2010

Mol Med

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Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.

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“…Paradoxically, the inflammatory and immune response to transplanted cells is also known to lead to behavioral improvements [4] indicating that the relationship between functional repair and graft survival is not as straightforward as it is often assumed. It also remains largely unknown how additional Limiting these anatomical analyses to post-mortem excised tissue, nonetheless, confines this approach to a snapshot view of the histological landscape and therefore complicates assertions as to how changes occurred or how these relate to behavioral improvements [9].…”

Section: How Do Neural Stem Cells Promote Behavioral Recovery?mentioning

confidence: 99%

“…The ability to visualize detailed anatomy repeatedly and non-invasively in vivo offers the opportunity to investigate how stem cell transplantation affects the damaged brain [9]. Both magnetic resonance imaging (MRI) and positron emission tomography (PET) are excellent in vivo imaging techniques to probe cell therapy in both preclinical models and clinical applications ( Table 1).…”

Section: The Necessity Of In Vivo Imaging To Elucidate Stem Cell-medimentioning

confidence: 99%

Understanding Stem Cell-Mediated Brain Repair Through Neuroimaging

Modo¹

2006

CSCR

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Transplantation of stem cells into the damaged brain can lead to behavioral recovery. However, at present, the mechanisms by which these cells exert their beneficial effects are still poorly understood. Survival, migration and differentiation are but a few of the factors that are thought to be involved in stem cell-mediated brain repair. It is hoped that neuroimaging, by MRI and PET, will provide serial in vivo assessments of transplanted cells that can lead to a greater understanding of the mechanisms involved in brain repair.

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In vivo monitoring of cellular transplants by magnetic resonance imaging and positron emission tomography

Cited by 19 publications

References 97 publications

Long‐term magnetic resonance imaging of stem cells in neonatal ischemic injury

Long‐term magnetic resonance imaging of stem cells in neonatal ischemic injury

Stem Cell Transplantation in Brain Tumors: A New Field for Molecular Imaging?

Understanding Stem Cell-Mediated Brain Repair Through Neuroimaging

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