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

• Published in: Stroke (1970) Vol. 39; no. 5; pp. 1569 - 1574
• Main Authors: WALCZAK, Piotr, JIAN ZHANG, GILAD, Assaf A, KEDZIOREK, Dorota A, RUIZ-CABELLO, Jesus, YOUNG, Randell G, PITTENGER, Mark F, VAN ZIJL, Peter C. M, JUDY HUANG, BULTE, Jeff W. M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.05.2008
• Subjects: Animals; Biological and medical sciences; Brain Ischemia - therapy; Cell Movement - physiology; Cell Survival - physiology; Cells, Cultured; Cerebral Arteries - pathology; Cerebral Arteries - physiopathology; Cerebral Arteries - surgery; Cerebrovascular Circulation - physiology; Female; Graft Survival - physiology; Ischemic Attack, Transient - therapy; Laser-Doppler Flowmetry - methods; Magnetic Resonance Imaging - methods; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Monitoring, Intraoperative - methods; Neurology; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rats; Rats, Inbred F344; Rats, Wistar; Stroke - therapy; Treatment Outcome; Vascular diseases and vascular malformations of the nervous system; Doppler ultrasound study; stem cells; Stroke; Nervous system diseases; MRI; Cardiovascular disease; laser Doppler flow; Nuclear magnetic resonance imaging; Cerebral disorder; Vascular disease; Ischemia; Central nervous system disease; Laser; transplantation; Monitoring; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.107.502047

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. 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 (4.7 T) and ex vivo (9.4 T). 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. 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.