Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI.

Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI.
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使用 Ferumoxytol 增强 MRI 追踪小型猪软骨缺损中的干细胞植入物。

DOI:
10.1148/radiol.2019182176
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发表时间:
2019
期刊:
影响因子:
19.7
通讯作者:
Daldrup-Link,HeikeE
Daldrup-Link,HeikeE
中科院分区:
医学1区
文献类型:
--
作者:
Theruvath,AshokJ;Nejadnik,Hossein;Lenkov,Olga;Yerneni,Ketan;Li,Kai;Kuntz,Lara;Wolterman,Cody;Tuebel,Jutta;Burgkart,Rainer;Liang,Tie;Felt,Stephen;Daldrup-Link,HeikeE

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背景:基质相关干细胞植入物(MASIs)在患者中的肱骨修复结果具有高度可变性。常规MRI不能帮助区分移植物,将和移植物,将不会修复下面的软骨缺损,直到许多个月后的repair.PurposeTo确定是否ferumoxytol纳米颗粒标记可以用来描绘成功或失败的MASIs相比,在大型动物模型中的常规MRI。材料和方法2016年1月至2017年12月,10哥廷根小型猪(n= 5名男性;n= 5名女性;平均年龄,6个月± 5.1;年龄范围,4-20个月)在股骨远端的软骨缺损中接受未标记(n= 12)或ferumoxytol标记(n= 20)的活的和凋亡的MASI的植入物。在第1周和第2、4、8、12和24周,在3.0 T成像单元上对所有MASI进行连续MRI成像,计算T2弛豫时间。通过使用软骨修复组织的MR观察(MOCART)评分(量表,0-100)、Pineda评分和软骨缺损中胶原2产生的组织病理学定量来评估软骨再生结果。结果进行了比较,通过使用非配对Wilcoxon秩和检验,线性回归模型,Fisher精确检验,Pearson correlation. ResultsFerumoxytol标记的MASIs显示出显着的T2缩短(22.2毫秒± 3.2与27.9毫秒± 1.8;P<0.001)和软骨修复的结果与未标记的对照MASIs(P> 0.05)相比,没有差异。在植入后第2周,与ferumoxytol标记的活性MASI相比,ferumoxytol标记的凋亡MASI显示铁信号丢失和更高的T2弛豫时间(26.6 msec ± 4.9 vs 20.8 msec ± 5.3;P= 0.001)。标准MRI显示24周时凋亡MASI的软骨缺损修复不完全。2周时的铁信号丢失与软骨修复不完全相关,在12-24周时的组织病理学检查中诊断。结论Ferumoxytol纳米颗粒标记可以在大型动物模型中加速MRI诊断成功和失败的基质相关干细胞植入。© RSNA,2019另见Sneag和Potter的社论。
BackgroundCartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair.PurposeTo determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model.Materials and MethodsBetween January 2016 and December 2017, 10 Göttingen minipigs (n= 5 male;n= 5 female; mean age, 6 months ± 5.1; age range, 4–20 months) received implants of unlabeled (n= 12) or ferumoxytol-labeled (n= 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0–100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation.ResultsFerumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8;P< .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P> .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3;P= .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12–24 weeks.ConclusionFerumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model.© RSNA, 2019See also the editorial by Sneag and Potter in this issue.
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