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Imaging transplanted stem cells in real time using an MRI dual-contrast method.

Ngen EJ, Wang L, Kato Y, Krishnamachary B, Zhu W, Gandhi N, Smith B, Armour M, Wong J, Gabrielson K, Artemov D - Sci Rep (2015)

Bottom Line: All results were validated with bioluminescence imaging.Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death.Ultimately, this technique could be used to manage stem cell therapies.

View Article: PubMed Central - PubMed

Affiliation: The In vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.

ABSTRACT
Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

No MeSH data available.


Related in: MedlinePlus

Phantom imaging of cell death detection.(a) BLI and corresponding T1 maps, and T1 images of 2% (w/v) agarose gel, on which were placed respective samples of live and dead luciferase-transduced and dual magnetically labelled cells. () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (b) T1 maps of 2% (w/v) agarose gel and corresponding longitudinal relaxation rate changes (%ΔR1) along the tubes, on which were placed respective dead cell samples (n = 3). () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (c) T2 maps of 2% (w/v) agarose gel containing the respective dead cell samples, and corresponding transverse relaxation rate changes (%ΔR2) along the tubes (n = 3). (d) Comparison of longitudinal (ΔR1) and transverse (ΔR2) relaxation rate changes of 2% (w/v) agarose gel, ~10 pixels from the surface, on which were placed dead cell samples (n = 3, P < 0.0001). (e) Changes in longitudinal (ΔR1) and transverse (ΔR2) relaxation rates of 2% (w/v) agarose gel with varying densities of dual magnetically labelled live cells (n = 3, P < 0.0001). (f) Changes in longitudinal relaxation rates (ΔR1) of 2% (w/v) agarose gel pads, ~10 pixels from the cell placement surfaces (n = 3, P < 0.0212). Samples were prepared with varying densities of dual magnetically labelled dead cells to estimate the cell death detection limits. () represents T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells.
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f5: Phantom imaging of cell death detection.(a) BLI and corresponding T1 maps, and T1 images of 2% (w/v) agarose gel, on which were placed respective samples of live and dead luciferase-transduced and dual magnetically labelled cells. () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (b) T1 maps of 2% (w/v) agarose gel and corresponding longitudinal relaxation rate changes (%ΔR1) along the tubes, on which were placed respective dead cell samples (n = 3). () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (c) T2 maps of 2% (w/v) agarose gel containing the respective dead cell samples, and corresponding transverse relaxation rate changes (%ΔR2) along the tubes (n = 3). (d) Comparison of longitudinal (ΔR1) and transverse (ΔR2) relaxation rate changes of 2% (w/v) agarose gel, ~10 pixels from the surface, on which were placed dead cell samples (n = 3, P < 0.0001). (e) Changes in longitudinal (ΔR1) and transverse (ΔR2) relaxation rates of 2% (w/v) agarose gel with varying densities of dual magnetically labelled live cells (n = 3, P < 0.0001). (f) Changes in longitudinal relaxation rates (ΔR1) of 2% (w/v) agarose gel pads, ~10 pixels from the cell placement surfaces (n = 3, P < 0.0212). Samples were prepared with varying densities of dual magnetically labelled dead cells to estimate the cell death detection limits. () represents T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells.

Mentions: In phantoms containing dead cells, a diffused T1 contrast was generated in the vicinity of the cells on T1 maps and T1-weighted images (Fig. 5a). This suggested the diffusion of GdDTPA, released from the dead cells. Cell death and cell viability in the respective phantoms was confirmed with BLI following MRI (Fig. 5a).


Imaging transplanted stem cells in real time using an MRI dual-contrast method.

Ngen EJ, Wang L, Kato Y, Krishnamachary B, Zhu W, Gandhi N, Smith B, Armour M, Wong J, Gabrielson K, Artemov D - Sci Rep (2015)

Phantom imaging of cell death detection.(a) BLI and corresponding T1 maps, and T1 images of 2% (w/v) agarose gel, on which were placed respective samples of live and dead luciferase-transduced and dual magnetically labelled cells. () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (b) T1 maps of 2% (w/v) agarose gel and corresponding longitudinal relaxation rate changes (%ΔR1) along the tubes, on which were placed respective dead cell samples (n = 3). () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (c) T2 maps of 2% (w/v) agarose gel containing the respective dead cell samples, and corresponding transverse relaxation rate changes (%ΔR2) along the tubes (n = 3). (d) Comparison of longitudinal (ΔR1) and transverse (ΔR2) relaxation rate changes of 2% (w/v) agarose gel, ~10 pixels from the surface, on which were placed dead cell samples (n = 3, P < 0.0001). (e) Changes in longitudinal (ΔR1) and transverse (ΔR2) relaxation rates of 2% (w/v) agarose gel with varying densities of dual magnetically labelled live cells (n = 3, P < 0.0001). (f) Changes in longitudinal relaxation rates (ΔR1) of 2% (w/v) agarose gel pads, ~10 pixels from the cell placement surfaces (n = 3, P < 0.0212). Samples were prepared with varying densities of dual magnetically labelled dead cells to estimate the cell death detection limits. () represents T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells.
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Related In: Results  -  Collection

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f5: Phantom imaging of cell death detection.(a) BLI and corresponding T1 maps, and T1 images of 2% (w/v) agarose gel, on which were placed respective samples of live and dead luciferase-transduced and dual magnetically labelled cells. () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (b) T1 maps of 2% (w/v) agarose gel and corresponding longitudinal relaxation rate changes (%ΔR1) along the tubes, on which were placed respective dead cell samples (n = 3). () represents diffused T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells. (c) T2 maps of 2% (w/v) agarose gel containing the respective dead cell samples, and corresponding transverse relaxation rate changes (%ΔR2) along the tubes (n = 3). (d) Comparison of longitudinal (ΔR1) and transverse (ΔR2) relaxation rate changes of 2% (w/v) agarose gel, ~10 pixels from the surface, on which were placed dead cell samples (n = 3, P < 0.0001). (e) Changes in longitudinal (ΔR1) and transverse (ΔR2) relaxation rates of 2% (w/v) agarose gel with varying densities of dual magnetically labelled live cells (n = 3, P < 0.0001). (f) Changes in longitudinal relaxation rates (ΔR1) of 2% (w/v) agarose gel pads, ~10 pixels from the cell placement surfaces (n = 3, P < 0.0212). Samples were prepared with varying densities of dual magnetically labelled dead cells to estimate the cell death detection limits. () represents T1 contrast enhancement in the vicinity of dead dual magnetically labelled cells.
Mentions: In phantoms containing dead cells, a diffused T1 contrast was generated in the vicinity of the cells on T1 maps and T1-weighted images (Fig. 5a). This suggested the diffusion of GdDTPA, released from the dead cells. Cell death and cell viability in the respective phantoms was confirmed with BLI following MRI (Fig. 5a).

Bottom Line: All results were validated with bioluminescence imaging.Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death.Ultimately, this technique could be used to manage stem cell therapies.

View Article: PubMed Central - PubMed

Affiliation: The In vivo Cellular and Molecular Imaging Center, Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.

ABSTRACT
Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

No MeSH data available.


Related in: MedlinePlus