Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury.
Long-term magnetic resonance imaging of stem cells in neonatal ischemic injury.
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DOI：
10.1002/ana.22168
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发表时间：
2011-02
影响因子：
11.2
通讯作者：
Ashwal, Stephen
中科院分区：
文献类型：
--
作者：
Obenaus, Andre;Dilmac, Nejmi;Tone, Beatriz;Tian, Hou Rou;Hartman, Richard;Digicaylioglu, Murat;Snyder, Evan Y.;Ashwal, Stephen
定量磁共振成像（MRI）可以连续、无创地评价大鼠缺氧缺血性损伤（HII）模型的损伤程度。它还可以在氧化铁预标记后非侵入性地监测干细胞迁移。有报道表明，神经干细胞（NSC）可能有助于介导神经保护或刺激成人和新生儿缺血性损伤模型的神经修复反应。我们研究了高场MRI在真实的时间内监测和非侵入性量化氧化铁标记的NSC在很长时间内（58周）的迁移、增殖和位置的能力，同时将这种活动与神经损伤的严重程度和程度相关联。将标记的克隆鼠NSC在10日龄大鼠幼仔的单侧HII后3天植入对侧纹状体或脑室中。我们开发了客观量化动态NSC行为关键方面的方法（例如，存活力;迁移的程度和速度;增殖程度;整合到宿主实质中的程度）。MRI图像与组织学和免疫组化评估进行了验证。mNSCs迅速迁移（100μm/天）至病变部位。胼胝体内可见迁移神经干细胞的链状结构。在接受HII的幼仔中，尽管在完整的对照动物中没有，但我们观察到植入后4周MR衍生的mNSC体积增加了273%（与内源性和外源性NSC的已知增殖行为相关），在58周的时间过程中缓慢下降，没有不良后果。大量现在静止的mNSCs留在损伤部位，许多保留了它们的氧化铁标记。我们的研究表明，MRI可以同时监测新生儿脑损伤以及NSC的迁移和定位。最重要的是，它可以非侵入性地监测增殖动态延长的时间段。为了能够在新生儿中进行使用干细胞疗法的临床试验，通过长期真实的时间监测细胞命运和活性来确保安全性是不言自明的，特别是在观察对发育中的大脑的意外风险方面。这项研究支持可靠地使用MRI用于此目的的可行性。
Quantitative magnetic resonance imaging (MRI) can serially and non-invasively assess the degree of injury in rat pup models of hypoxic ischemic injury (HII). It can also non-invasively monitor stem cell migration following iron oxide pre-labeling. Reports have shown that neural stem cells (NSCs) may help mediate neuroprotection or stimulate neuroreparative responses in adult and neonatal models of ischemic injury. We investigated the ability of high-field MRI to monitor and non-invasively quantify the migration, proliferation, and location of iron oxide-labeled NSCs over very long time periods (58 weeks) in real time while contemporaneously correlating this activity with the evolving severity and extent of neural damage. Labeled clonal murine NSCs were implanted 3 days after unilateral HII in 10 day old rat pups into the contralateral striatum or ventricle. We developed methods for objectively quantifying key aspects of dynamic NSC behavior (e.g., viability; extent and speed of migration; degree of proliferation; extent of integration into host parenchyma). MRI images were validated with histological and immunohistochemical assessments. mNSCs rapidly migrated (100μm/day) to the lesion site. Chains of migrating NSCs were observed in the corpus callosum. In pups subjected to HII, though not in intact control animals, we observed a 273% increase in the MR-derived volume of mNSCs 4 weeks after implantation (correlating with the known proliferative behavior of endogenous and exogenous NSCs) that slowly declined over the 58 week time course, with no adverse consequences. Large numbers of now quiescent mNSCs remained at the site of injury, many retaining their iron oxide label. Our studies demonstrate that MRI can simultaneously monitor evolving neonatal cerebral injury as well as NSC migration and location. Most importantly, it can non-invasively monitor proliferation dynamically for prolonged time periods. To be able to pursue clinical trials in newborns using stem cell therapies, it is axiomatic that safety be insured through the long-term real time monitoring of cell fate and activity, particularly with regard to observing unanticipated risks to the developing brain. This study supports the feasibility of reliably using MRI for this purpose.
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影响因子：
3.3
作者：
Ben-Hur, Tamir;van Heeswijk, Ruud B.;Bulte, Jeff W. M.
通讯作者：
Bulte, Jeff W. M.
影响因子：
3.3
作者：
Irons, H;Lind, JG;Borlongan, CV
通讯作者：
Borlongan, CV
影响因子：
3.4
作者：
Kameda, M.;Shingo, T.;Date, I.
通讯作者：
Date, I.
影响因子：
168.9
作者：
Gluckman, PD;Wyatt, JS;Gunn, AJ
通讯作者：
Gunn, AJ
DOI：
10.1073/pnas.0915134107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Jaderstad, Johan;Jaderstad, Linda M.;Herlenius, Eric
通讯作者：
Herlenius, Eric