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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

Schematic representing live cell-tracking by T2/T2* contrast enhancement, and cell death detection by T1 contrast enhancement.A diffused T1 contrast enhancement is generated in the vicinity of dead cells on T1-weighted MR images, and serves as a local imaging marker of cell death. This diffused T1 contrast enhancement is not observed in the vicinity of live cells.
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f1: Schematic representing live cell-tracking by T2/T2* contrast enhancement, and cell death detection by T1 contrast enhancement.A diffused T1 contrast enhancement is generated in the vicinity of dead cells on T1-weighted MR images, and serves as a local imaging marker of cell death. This diffused T1 contrast enhancement is not observed in the vicinity of live cells.

Mentions: We hypothesized that, in live cells, where both contrast agents are entrapped in confined cellular spaces and remain in close proximity to each other, a strong T2/T2* contrast would be generated by the labelled cells. The T1 contrast of the gadolinium chelates in the labelled cells would be quenched383941. Upon cell death, the plasma membranes of the transplanted cells would be breached42. The small-sized, fast-diffusing, gadolinium chelates would then diffuse away from the slow-diffusing SPIONs and generate a diffused T1 contrast enhancement in the vicinity of the dead cells (Fig. 1). This dynamic T1 contrast enhancement in the vicinity of the transplanted cells would then serve as a local imaging marker for cell death. The different MRI signatures (T2/T2* and T1) would be distinguishable using an MRI spin echo pulse sequence with appropriate acquisition parameters. Based on our previous studies, we determined that it is possible to separate both T2/T2* and T1 signals using appropriate acquisition parameters, when both agents are as little as ~15 μm away from each other3839.


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)

Schematic representing live cell-tracking by T2/T2* contrast enhancement, and cell death detection by T1 contrast enhancement.A diffused T1 contrast enhancement is generated in the vicinity of dead cells on T1-weighted MR images, and serves as a local imaging marker of cell death. This diffused T1 contrast enhancement is not observed in the vicinity of live cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556978&req=5

f1: Schematic representing live cell-tracking by T2/T2* contrast enhancement, and cell death detection by T1 contrast enhancement.A diffused T1 contrast enhancement is generated in the vicinity of dead cells on T1-weighted MR images, and serves as a local imaging marker of cell death. This diffused T1 contrast enhancement is not observed in the vicinity of live cells.
Mentions: We hypothesized that, in live cells, where both contrast agents are entrapped in confined cellular spaces and remain in close proximity to each other, a strong T2/T2* contrast would be generated by the labelled cells. The T1 contrast of the gadolinium chelates in the labelled cells would be quenched383941. Upon cell death, the plasma membranes of the transplanted cells would be breached42. The small-sized, fast-diffusing, gadolinium chelates would then diffuse away from the slow-diffusing SPIONs and generate a diffused T1 contrast enhancement in the vicinity of the dead cells (Fig. 1). This dynamic T1 contrast enhancement in the vicinity of the transplanted cells would then serve as a local imaging marker for cell death. The different MRI signatures (T2/T2* and T1) would be distinguishable using an MRI spin echo pulse sequence with appropriate acquisition parameters. Based on our previous studies, we determined that it is possible to separate both T2/T2* and T1 signals using appropriate acquisition parameters, when both agents are as little as ~15 μm away from each other3839.

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