Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells in Cartilage Defects: In Vitro and In Vivo Investigations

Magnetic Resonance Imaging of Ferumoxide-Labeled Mesenchymal Stem Cells in Cartilage Defects: In Vitro and In Vivo Investigations
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DOI:
10.2310/7290.2011.00040
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发表时间:
2012-05-01
期刊:
影响因子:
2.8
通讯作者:
Daldrup-Link, Heike E.
Daldrup-Link, Heike E.
中科院分区:
医学4区
文献类型:
--
作者:
Henning, Tobias D.;Gawande, Rakhee;Daldrup-Link, Heike E.

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本研究的目的是:(1)比较阿魏氧化素标记间充质干细胞(MSCs)的三种不同技术,(2)评估阿魏氧化素标记是否允许在动物模型中对基质相关干细胞植入物(MASIs)进行体内跟踪,(3)比较阿魏氧化素标记的活的和凋亡的MSCs的磁共振成像(MRI)特征。通过简单孵育、鱼精蛋白转染或脂质体转染阿鲁莫西标记的间充质干细胞用MRI和组织病理学进行评估。采用MRI对大鼠膝关节骨软骨缺损中经阿魏标记和未标记的活的和凋亡的间充质干细胞进行12周的观察。用t检验检验活的和凋亡标记的mais的信噪比(SNRs)是否有显著差异。一个简单的孵育标记方案证明了显著的磁共振信号效应与保存细胞活力和潜在的即时临床转化之间的最佳折衷。标记活的和凋亡的MASIs在信噪比上没有显着差异。随着时间的推移,标记有活力但未凋亡的间充质干细胞显示出T-2信号丢失面积的增加,这与移植部位的干细胞增殖有关。组织病理学证实存活的MSCs成功植入。通过简单的培养,可以用MRI监测几周内氧化铁标记的mais的植入情况。可通过移植部位细胞增殖的影像学征象来区分存活的和凋亡的MASIs。
The purpose of this study was to (1) compare three different techniques for ferumoxide labeling of mesenchymal stem cells (MSCs), (2) evaluate if ferumoxide labeling allows in vivo tracking of matrix-associated stem cell implants (MASIs) in an animal model, and (3) compare the magnetic resonance imaging (MRI) characteristics of ferumoxide-labeled viable and apoptotic MSCs. MSCs labeled with ferumoxide by simple incubation, protamine transfection, or Lipofectin transfection were evaluated with MRI and histopathology. Ferumoxide-labeled and unlabeled viable and apoptotic MSCs in osteochondral defects of rat knee joints were evaluated over 12 weeks with MRI. Signal to noise ratios (SNRs) of viable and apoptotic labeled MASIs were tested for significant differences using t-tests. A simple incubation labeling protocol demonstrated the best compromise between significant magnetic resonance signal effects and preserved cell viability and potential for immediate clinical translation. Labeled viable and apoptotic MASIs did not show significant differences in SNR. Labeled viable but not apoptotic MSCs demonstrated an increasing area of T-2 signal loss over time, which correlated to stem cell proliferation at the transplantation site. Histopathology confirmed successful engraftment of viable MSCs. The engraftment of iron oxide-labeled MASIs by simple incubation can be monitored over several weeks with MRI. Viable and apoptotic MASIs can be distinguished via imaging signs of cell proliferation at the transplantation site.