This Article Full Text Full Text (PDF) All Versions of this Article: 39/5/1569    most recent STROKEAHA.107.502047v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Walczak, P. Articles by Bulte, J. W.M. PubMed PubMed Citation Articles by Walczak, P. Articles by Bulte, J. W.M. Related Collections Imaging

(Stroke. 2008;39:1569.)
© 2008 American Heart Association, Inc.

Original Contributions

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 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.

Correspondence to Jeff W.M. Bulte, PhD, Russell H. Morgan Dept. of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 217 Traylor, 720 Rutland Ave, Baltimore, MD 21205-2195. 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