MRI/SPECT/Fluorescent Tri-Modal Probe for Evaluating the Homing and Therapeutic Efficacy of Transplanted Mesenchymal Stem Cells in a Rat Ischemic Stroke Model.
Quantitatively tracking engraftment of intracerebrally or intravenously transplanted stem cells and evaluating their concomitant therapeutic efficacy for stroke has been a challenge in the field of stem cell therapy. In this study, first, an MRI/SPECT/fluorescent tri-modal probe (125I-fSiO4@SPIOs) is synthesized for quantitatively tracking mesenchymal stem cells (MSCs) transplanted intracerebrally or intravenously into stroke rats, and then the therapeutic efficacy of MSCs delivered by both routes and the possible mechanism of the therapy are evaluated. It is demonstrated that(125)I-fSiO4@SPIOs have high efficiency for labeling MSCs without affecting their viability, differentiation, and proliferation capacity, and found that 35% of intracerebrally injected MSCs migrate along the corpus callosum to the lesion area, while 90% of intravenously injected MSCs remain trapped in the lung at 14 days after MSC transplantation. However, neurobehavioral outcomes are significantly improved in both transplantation groups, which are accompanied by increases of vascular endothelial growth factor, basic fibroblast growth factor, and tissue inhibitor of metalloproteinases-3 in blood, lung, and brain tissue (p< 0.05). The study demonstrates that125I-fSiO4@SPIOs are robust probe for long-term tracking of MSCs in the treatment of ischemic brain and MSCs delivered via both routes improve neurobehavioral outcomes in ischemic rats.
State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Yaohui
Y
Tang
State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Chunfu
C
Zhang
Department of Neurology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Jixian
J
Wang
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Xiaojie
X
Lin
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Lu
L
Zhang
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Yi
Y
Yang
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Yongting
Y
Wang
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Zhijun
Z
Zhang
Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jeff W M
JW
Bulte
School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
Guo-Yuan
GY
Yang