Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia

被引：334

作者：

Walczak, Piotr ^{[1
,2
]}

Zhang, Jian ^{[3
]}

Gilad, Assaf A. ^{[1
,2
]}

Kedziorek, Dorota A. ^{[1
,2
]}

Ruiz-Cabello, Jesus ^{[1
,2
]}

Young, Randell G. ^{[6
]}

Pittenger, Mark F. ^{[6
]}

Van Zijl, Peter C. M. ^{[1
,5
,7
]}

Huang, Judy ^{[3
]}

Bulte, Jeff W. M. ^{[1
,2
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Neurosect Div MR Res, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA

[2] Johns Hopkins Univ, Sch Med, Cellular Imaging Sect & Vasc Biol Program, Inst Cell Engn, Baltimore, MD USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD USA

[4] Johns Hopkins Univ, Sch Med, Dept Chem & Biomol Engn, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD USA

[6] Therapeut Inc, Baltimore, MD USA

[7] Kennedy Krieger Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD USA

来源：

STROKE | 2008年 / 39卷 / 05期

关键词：

laser Doppler flow; MRI; stroke; stem cells; transplantation;

D O I：

10.1161/STROKEAHA.107.502047

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：1569 / 1574

页数：6

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