Published Online
on March 6, 2008

A more recent version of this article appeared on May 1, 2008

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Submitted on August 15, 2007
Revised on September 20, 2007
Accepted on October 1, 2007

Dual-Modality Monitoring of Targeted Intraarterial Delivery of Mesenchymal Stem Cells After Transient Ischemia

Piotr Walczak MD; Jian Zhang MD; Assaf A. Gilad PhD; Dorota A. Kedziorek MD; Jesus Ruiz-Cabello PhD; Randell G. Young DVM; Mark F. Pittenger PhD; Peter C.M. van Zijl PhD; Judy Huang MD; and Jeff W.M. Bulte PhD^*

From the Neurosection, Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science (P.W., A.A.G., D.A.K., J.R.-C., P.C.M.v.Z., J.W.M.B.), the Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering (P.W., A.A.G., D.A.K., J.R.-C., J.W.M.B.), the Departments of Neurosurgery (J.Z., J.H.), Chemical and Biomolecular Engineering (J.W.M.B.), and Biomedical Engineering (J.W.M.B.), The Johns Hopkins University School of Medicine, Baltimore, Md; Osiris Therapeutics Inc (R.G.Y., M.F.P.), Baltimore Md; and F.M. Kirby Center for Functional Brain Imaging (P.C.M.v.Z.), Kennedy Krieger Institute, Baltimore, Md.

^* To whom correspondence should be addressed. E-mail: jwmbulte{at}mri.jhu.edu.

Background and Purpose—In animal models of stroke, functional improvement has been obtained after stem cell transplantation. Successful therapy depends largely on achieving a robust and targeted cell engraftment, with intraarterial (IA) injection being a potentially attractive route of administration. We assessed the suitability of laser Doppler flow (LDF) signal measurements and magnetic resonance (MR) imaging for noninvasive dual monitoring of targeted IA cell delivery.

Methods—Transient cerebral ischemia was induced in adult Wistar rats (n=25) followed by IA or intravenous (IV) injection of mesenchymal stem cells (MSCs) labeled with superparamagnetic iron oxide. Cell infusion was monitored in real time with transcranial laser Doppler flowmetry while cellular delivery was assessed with MRI in vivo (4.7T) and ex vivo (9.4T).

Results—Successful delivery of magnetically labeled MSCs could be readily visualized with MRI after IA but not IV injection. IA stem cell injection during acute stroke resulted in a high variability of cerebral engraftment. The amount of LDF reduction during cell infusion (up to 80%) was found to correlate well with the degree of intracerebral engraftment, with low LDF values being associated with significant morbidity.

Conclusions—High cerebral engraftment rates are associated with impeded cerebral blood flow. Noninvasive dual-modality imaging enables monitoring of targeted cell delivery, and through interactive adjustment may improve the safety and efficacy of stem cell therapy.

Key words: laser Doppler flow • MRI • stroke • stem cells • transplantation

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