Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia.
OBJECTIVE
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 (4.7 T) and ex vivo (9.4 T).


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.
Walczak
Piotr
P
Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 217 Traylor, 720 Rutland Ave, Baltimore, MD 21205-2195, USA.
Zhang
Jian
J
Gilad
Assaf A
AA
Kedziorek
Dorota A
DA
Ruiz-Cabello
Jesus
J
Young
Randell G
RG
Pittenger
Mark F
MF
van Zijl
Peter C M
PC
Huang
Judy
J
Bulte
Jeff W M
JW
D000818:Animals; D002545:Brain Ischemia / Q000628:therapy*; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006085:Graft Survival / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000628:therapy*; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D016343:Monitoring, Intraoperative / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D020521:Stroke / Q000628:therapy; D016896:Treatment Outcome