Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging.

Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging.
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DOI:
10.1186/1471-2342-12-33
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发表时间:
2012-12-06
影响因子:
2.7
通讯作者:
Chopp M
Chopp M
中科院分区:
医学4区
文献类型:
--
作者:
Arbab AS;Thiffault C;Navia B;Victor SJ;Hong K;Zhang L;Jiang Q;Varma NR;Iskander A;Chopp M

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为了增加对输注细胞如何工作的理解,重要的是跟踪它们在移植后的初始运动、定位和植入效率。然而,可用的体内细胞跟踪技术是次优的。本研究的目的是使用单光子发射计算机断层扫描(SPECT)确定静脉注射的铟-111(In-111)8-羟基喹啉标记的人脐组织衍生细胞(hUTC)在大鼠短暂性大脑中动脉闭塞(tMCAo)模型中的生物分布。大鼠接受300万In-111标记的hUTC(i. v.)tMCAo后48小时。在施用hUTC或等效剂量的In-111-oxine(18.5MBq)后,动物在第0、1和3天进行SPECT成像。测定各种器官以及卒中区域和对侧半球的放射性,校正衰变并归一化为第0天的总(全身,包括头部)放射性。还进行免疫组织化学分析以确认hUTC对血管和突触密度以及细胞凋亡的有益作用。在IV给予In-111标记的hUTC(第0天)后,大部分放射性(第0天为43.36±23.07%)立即转运至肺,并在注射后第1天和第3天分别急剧下降至8.81± 7.75%和4.01±4.52%。相比之下,在单独接受In-111-oxine的动物的肺中测量的放射性从第0天到第1天保持相对不变(从第0天的18.38±5.45%到12.59±5.94%),并在第3天降低到8.34±4.25%。在接受In-111标记的hUTC的动物的中风区域中观察到显著更高的放射性,表明在损伤部位存在细胞,约占总给药剂量的1%。此外,在接受In-111标记的hUTC的大鼠的中风区域中,血管和突触素免疫反应性显著增加。目前的研究显示,使用SPECT在大鼠tMCAo模型中追踪In-111标记的hUTC至中风部位。用In-111标记的hUTC治疗的动物显示组织学改善,在缺血边界区(IBZ)中观察到更高的血管和突触密度。
In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available in vivo cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT). Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals underwent SPECT imaging on days 0, 1, and 3. Radioactivity in various organs as well as in the stroke area and contralateral hemisphere was determined, decay corrected and normalized to the total (whole body including head) radioactivity on day 0. Immunohistochemical analysis was also performed to confirm the beneficial effects of hUTC on vascular and synaptic density, and apoptosis. Most of the radioactivity (43.36±23.07% on day 0) trafficked to the lungs immediately following IV administration of In-111 labeled hUTC (day 0) and decreased drastically to 8.81±7.75 and 4.01±4.52% on days 1 and 3 post-injection, respectively. In contrast, radioactivity measured in the lung of animals that received In-111-oxine alone remained relatively unchanged from day 0 to day 1 (18.38±5.45% at day 0 to 12.59±5.94%) and decreased to 8.34±4.25% on day 3. Significantly higher radioactivity was observed in stroke areas of animals that received In-111 labeled hUTC indicating the presence of cells at the site of injury representing approximately 1% of total administered dose. In addition, there was significant increase in vascular and synaptophysin immunoreactivity in stroke areas of rats that received In-111 labeled hUTC. The present studies showed the tracking of In-111 labeled hUTC to the sites of stroke in a rat model of tMCAo using SPECT. Animals treated with In-111 labeled hUTC showed histological improvements, with higher vascular and synaptic densities observed in the ischemic boundary zone (IBZ).
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