Imaging transplanted stem cells in real time using an MRI dual-contrast method.
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.
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.
Ethel J
EJ
Ngen
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.
Lee
L
Wang
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.|The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.
Yoshinori
Y
Kato
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.
Balaji
B
Krishnamachary
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.
Wenlian
W
Zhu
The Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD21287, USA.
Nishant
N
Gandhi
The Institute for Basic Biomedical Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.
Barbara
B
Smith
The Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD21287, USA.
Michael
M
Armour
The Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD21287, USA.
John
J
Wong
The Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.
Kathleen
K
Gabrielson
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.|The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD21205, USA.
Dmitri
D
Artemov
D000818:Animals; D001930:Brain Injuries / Q000175:diagnosis / Q000473:pathology; D016923:Cell Death; D002465:Cell Movement; D058948:Cell Tracking; D003287:Contrast Media / Q000737:chemistry*; D019786:Gadolinium DTPA; D006801:Humans; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism; D008163:Luminescent Measurements; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D019047:Phantoms, Imaging; D011832:Radiation Injuries / Q000175:diagnosis / Q000473:pathology; D013194:Staining and Labeling
D003287:Contrast Media; D007501:Iron; D019786:Gadolinium DTPA