Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI.

Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive R200, Stanford, CA 94305-5327, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 07/2007; 104(24):10211-6. DOI: 10.1073/pnas.0608519104
Source: PubMed

ABSTRACT Noninvasive monitoring of stem cells, using high-resolution molecular imaging, will be instrumental to improve clinical neural transplantation strategies. We show that labeling of human central nervous system stem cells grown as neurospheres with magnetic nanoparticles does not adversely affect survival, migration, and differentiation or alter neuronal electrophysiological characteristics. Using MRI, we show that human central nervous system stem cells transplanted either to the neonatal, the adult, or the injured rodent brain respond to cues characteristic for the ambient microenvironment resulting in distinct migration patterns. Nanoparticle-labeled human central nervous system stem cells survive long-term and differentiate in a site-specific manner identical to that seen for transplants of unlabeled cells. We also demonstrate the impact of graft location on cell migration and describe magnetic resonance characteristics of graft cell death and subsequent clearance. Knowledge of migration patterns and implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation.

Download full-text


Available from: Raphael Guzman, Jan 08, 2014
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The capacity to track cells (cell tracking) using x-rays on ex-vivo specimens of both malignant and non-malignant cell lines on small animals has been demonstrated recently. Gold nanoparticles have been used as a cellular contrast agent to render cells visible in x-ray microCT acquisitions. The limits of the technique proposed are basically driven by the imaging system used. Single cell resolution can be achieved using synchrotron radiation in-vitro or ex-vivo samples. Micro-focus x-ray tubes can be used to obtain high resolution cell tracking but with some limitations. However, the translation from ex-vivo to in-vivo experiments is not straightforward. The dose restrictions required for in-vivo longitudinal experiments set severe limitations on the technique. Here we present a detailed investigation showing a significant reduction of x-ray dose for the tracking of brain tumour cells. Monte Carlo simulations have been performed considering different spatial resolutions, photon fluence, number of projections, lesion dimension and cell contrast dilution. The findings are compared with real samples imaged using the same parameters. A pioneering in-vivo experiment conducted at the SYRMEP beamline (Elettra, Basovizza, Italy) is presented here as proof of principle of in-vivo longitudinal x-ray cell tracking experiments on small animals at low x-ray doses.
    Journal of Instrumentation 06/2013; 8(06):C06010. DOI:10.1088/1748-0221/8/06/C06010 · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Since their discovery twenty years ago and prospective isolation a decade later, neural stem cells (NSCs), their progenitors, and differentiated cell derivatives along with other stem-cell based strategies have advanced steadily toward clinical trials, spurred by the immense need to find reparative therapeutics for central nervous system (CNS) diseases and injury. Current phase I/II trials using stem cells in the CNS are the vanguard for the widely anticipated next generation of regenerative therapies and as such are pioneering the stem cell therapy process. While translation has typically been the purview of industry, academic researchers are increasingly driven to bring their findings toward treatments and face challenges in knowledge gap and resource access that are accentuated by the unique financial, manufacturing, scientific, and regulatory aspects of cell therapy. Solutions are envisioned that both address the significant unmet medical need and lead to increased funding for basic and translational research.
    Neuron 05/2011; 70(4):597-613. DOI:10.1016/j.neuron.2011.05.007 · 15.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-invasive identification of transplanted neural stem cells in vivo by pre-labelling with contrast agents may play an important role in the translation of cell therapy to the clinic. Understanding the impact of these labels on the cells' ability to repair is therefore vital. In rats with middle cerebral artery occlusion (MCAo), a model of stroke, the transhemispheric migration of MHP36 cells labelled with the bimodal contrast agent GRID was detected on magnetic resonance images (MRI) up to 4 weeks following transplantation. However, compared to MHP36 cells labelled with the red fluorescent dye PKH26, GRID-labelled transplants did not significantly improve behaviour, and performance was akin to non-treated animals. Likewise, the evolution of anatomical damage as assessed by serial, T(2)-weighted MRI over 1 year indicated that GRID-labelled transplants resulted in a slight increase in lesion size compared to MCAo-only animals, whereas the same, PKH26-labelled cells significantly decreased lesion size by 35%. Although GRID labelling allows the in vivo identification of transplanted cells up to 1 month after transplantation, it is likely that some is gradually degraded inside cells. The translation of cellular imaging therefore does not only require the in vitro assessment of contrast agents on cellular functions, but also requires the chronic, in vivo assessment of the label on the stem cells' ability to repair in preclinical models of neurological disease.
    NeuroImage 08/2009; 47 Suppl 2:T133-42. DOI:10.1016/j.neuroimage.2008.06.017 · 6.13 Impact Factor