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全脑缺血患者脑室内注射后长期的MRI细胞追踪及脑脊液中干细胞磁导航的前景

Long-term MRI cell tracking after intraventricular delivery in a patient with global cerebral ischemia and prospects for magnetic navigation of stem cells within the CSF.

作者信息

Janowski Miroslaw, Walczak Piotr, Kropiwnicki Tomasz, Jurkiewicz Elzbieta, Domanska-Janik Krystyna, Bulte Jeff W M, Lukomska Barbara, Roszkowski Marcin

机构信息

NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; Russell H. Morgan Department of Radiology and Radiological Science, Division of Magnetic Resonance Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Russell H. Morgan Department of Radiology and Radiological Science, Division of Magnetic Resonance Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.

出版信息

PLoS One. 2014 Jun 11;9(2):e97631. doi: 10.1371/journal.pone.0097631. eCollection 2014.


DOI:10.1371/journal.pone.0097631
PMID:24919061
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4053317/
Abstract

BACKGROUND: The purpose of the study was to evaluate the long-term clinical tracking of magnetically labeled stem cells after intracerebroventricular transplantation as well as to investigate in vitro feasibility for magnetic guidance of cell therapy within large fluid compartments. METHOD: After approval by our Institutional Review Board, an 18-month-old patient, diagnosed as being in a vegetative state due to global cerebral ischemia, underwent cell transplantation to the frontal horn of the lateral ventricle, with umbilical cord blood-derived stem cells labeled with superparamagnetic iron oxide (SPIO) contrast agent. The patient was followed over 33 months with clinical examinations and MRI. To evaluate the forces governing the distribution of cells within the fluid compartment of the ventricular system in vivo, a gravity-driven sedimentation assay and a magnetic field-driven cell attraction assay were developed in vitro. RESULTS: Twenty-four hours post-transplantation, MR imaging (MRI) was able to detect hypointense cells in the occipital horn of the lateral ventricle. The signal gradually decreased over 4 months and became undetectable at 33 months. In vitro, no significant difference in cell sedimentation between SPIO-labeled and unlabeled cells was observed (p = NS). An external magnet was effective in attracting cells over distances comparable to the size of human lateral ventricles. CONCLUSIONS: MR imaging of SPIO-labeled cells allows monitoring of cells within lateral ventricles. While the initial biodistribution is governed by gravity-driven sedimentation, an external magnetic field may possibly be applied to further direct the distribution of labeled cells within large fluid compartments such as the ventricular system.

摘要

背景:本研究的目的是评估脑室内移植后磁性标记干细胞的长期临床追踪情况,并研究在大型液体腔室内进行细胞治疗磁导向的体外可行性。 方法:经我们机构审查委员会批准,一名18个月大、因全脑缺血被诊断为植物人的患者接受了向侧脑室额角的细胞移植,移植的是用超顺磁性氧化铁(SPIO)造影剂标记的脐带血来源干细胞。对该患者进行了33个月的临床检查和磁共振成像(MRI)随访。为了评估体内控制细胞在脑室系统液体腔内分布的力,在体外开展了重力驱动沉降试验和磁场驱动细胞吸引试验。 结果:移植后24小时,磁共振成像(MRI)能够在侧脑室枕角检测到低信号细胞。信号在4个月内逐渐降低,在33个月时无法检测到。在体外,未观察到SPIO标记细胞和未标记细胞在细胞沉降方面有显著差异(p = 无统计学意义)。外部磁铁能够有效地在与人类侧脑室大小相当的距离内吸引细胞。 结论:SPIO标记细胞的MRI可用于监测侧脑室内的细胞。虽然初始生物分布受重力驱动沉降的控制,但外部磁场可能可用于进一步引导标记细胞在大型液体腔室(如脑室系统)内的分布。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/a6cd826e0df6/pone.0097631.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/334035d2a44d/pone.0097631.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/e4a853184512/pone.0097631.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/230f11ba20f1/pone.0097631.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/a6cd826e0df6/pone.0097631.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/334035d2a44d/pone.0097631.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/e4a853184512/pone.0097631.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/230f11ba20f1/pone.0097631.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14f1/4053317/a6cd826e0df6/pone.0097631.g004.jpg

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本文引用的文献

[1]
Intracerebroventricular Transplantation of Cord Blood-Derived Neural Progenitors in a Child With Severe Global Brain Ischemic Injury.

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