TY - JOUR
T1 - Imaging transplanted stem cells in real time using an MRI dual-contrast method
AU - Ngen, Ethel J.
AU - Wang, Lee
AU - Kato, Yoshinori
AU - Krishnamachary, Balaji
AU - Zhu, Wenlian
AU - Gandhi, Nishant
AU - Smith, Barbara
AU - Armour, Michael
AU - Wong, John
AU - Gabrielson, Kathleen
AU - Artemov, Dmitri
N1 - Funding Information:
The authors would like to thank Dr. Zaver M. Bhujwalla for her support; Dr. Jiangyang Zhang; Dr. Venu Raman; Dr. Farhad Vesuna; and Dr. Sudath Hapuarachchige for their helpful discussions; Ms. Jana Mihalic; Mr. Joshua Crawford; and Mr. Kevin Rhie for their technical assistance; and Ms. Mary McAllister for editing this manuscript. This research was sponsored by the TEDCO Maryland Stem Cell Research Fund (2010-MSCRFE-0096), the National Institutes of Health (grant numbers: R01CA136576 and P50CA103175) and the American Brain Tumor Association (grant numbers: 117704 - ABTA Basic Research).
PY - 2015/9/2
Y1 - 2015/9/2
N2 - 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 (T 2 /T 2 ∗) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T 1) 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.
AB - 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 (T 2 /T 2 ∗) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T 1) 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.
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U2 - 10.1038/srep13628
DO - 10.1038/srep13628
M3 - Article
C2 - 26330231
AN - SCOPUS:84940883689
SN - 2045-2322
VL - 5
JO - Scientific reports
JF - Scientific reports
M1 - 13628
ER -