Real-time MRI for precise and predictable intra-arterial stem cell delivery to the central nervous system.
Stem cell therapy for neurological disorders reached a pivotal point when the efficacy of several cell types was demonstrated in small animal models. Translation of stem cell therapy is contingent upon overcoming the challenge of effective cell delivery to the human brain, which has a volume ∼1000 times larger than that of the mouse. Intra-arterial injection can achieve a broad, global, but also on-demand spatially targeted biodistribution; however, its utility has been limited by unpredictable cell destination and homing as dictated by the vascular territory, as well as by safety concerns. We show here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus be used to accurately predict the distribution of intra-arterial administered stem cells. Moreover, high-speed MRI enables the real-time visualization of cell homing, providing the opportunity for immediate intervention in the case of undesired biodistribution.
1 Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|2 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|3 Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
Piotr
P
Walczak
4 Department of Pathophysiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
Joanna
J
Wojtkiewicz
5 NeuroRepair Dept, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Adam
A
Nowakowski
4 Department of Pathophysiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
Aleksandra
A
Habich
6 Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland.
Piotr
P
Holak
7 F.M. Kirby Research Centre, Kennedy Krieger Institute, Baltimore, MD, USA.
Jiadi
J
Xu
6 Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland.
Zbigniew
Z
Adamiak
1 Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Moussa
M
Chehade
8 Division of Interventional Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Monica S
MS
Pearl
8 Division of Interventional Neuroradiology, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Philippe
P
Gailloud
5 NeuroRepair Dept, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Barbara
B
Lukomska
9 Department of Neurology and Neurosurgery, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
Wojciech
W
Maksymowicz
1 Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|2 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|10 Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|11 Department of Chemical & Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|12 Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeff Wm
JW
Bulte
1 Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|2 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|5 NeuroRepair Dept, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.|13 Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Miroslaw
M
Janowski
D000818:Animals; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D058948:Cell Tracking / Q000379:methods*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D004285:Dogs; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D020521:Stroke / Q000000981:diagnostic imaging / Q000628:therapy*; D013552:Swine
Intra-arterial; MRI; iron oxide; real-time; stroke