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Abstract
BackgroundThis study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model.MethodologyMSCs harvested from beagles’ bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×106 labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks.Principal FindingsHome-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining.ConclusionIt is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.
Highlights
Stem cell based therapies have been shown to improve functional outcome in many experimental stroke
Grafted mesenchymal stem cells (MSCs) could be tracked effectively by Magnetic resonance imaging (MRI) within four weeks and were found in peri-infarction area by Prussian blue staining. It is feasible of IA MSCs transplantation in a canine stroke model
In vivo MR imaging is useful for tracking IA delivered MSCs after superparamagnetic iron oxide (SPIO) labeling
Summary
Stem cell based therapies have been shown to improve functional outcome in many experimental stroke. Because of relatively low immunogenicity and easy way of isolation, many studies used mesenchymal stem cells (MSCs) for stroke and suggested their effectiveness in cerebral ischemia. Most of those studies were performed in rodents with intravenous or stereotactic injection of stem cells [4,9,10]. The intraarterial (IA) route of delivery, given that the fist pass of MSCs would be brain, seems better and enables widespread cerebral engraftment of cells. This study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model
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