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影像引导下经动脉定向递送人骨髓间充质干细胞用于猪模型中的胃肠道靶向治疗。

Image-Guided Transarterial Directed Delivery of Human Mesenchymal Stem Cells for Targeted Gastrointestinal Therapies in a Swine Model.

机构信息

Department of Radiology and Imaging Sciences, Emory University, 201 Dowman Drive, Atlanta, GA 30322.

Division of Animal Resources, Emory University, 201 Dowman Drive, Atlanta, GA 30322.

出版信息

J Vasc Interv Radiol. 2019 Jul;30(7):1128-1134.e5. doi: 10.1016/j.jvir.2018.09.034. Epub 2019 Mar 6.

DOI:10.1016/j.jvir.2018.09.034
PMID:30852052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6589393/
Abstract

PURPOSE

To evaluate the feasibility of catheter-directed intra-arterial stem cell delivery of human mesenchymal stem cells (MSCs) to the small bowel in a porcine model.

MATERIALS AND METHODS

The cranial mesenteric artery of 6 Yucatan minipigs was selectively catheterized under fluoroscopic guidance following cut-down and carotid artery access. A proximal jejunal branch artery was selectively catheterized for directed delivery of embolic microspheres (100-300 μm) or MSCs (0.1-10 million cells). The pigs were euthanized after 4 hours and specimens collected from the proximal duodenum and the targeted segment of the jejunum. The Chiu/Park system for scoring intestinal ischemia was used to compare hematoxylin and eosin-stained sections of jejunum and duodenum.

RESULTS

Successful delivery of microspheres or MSCs in a proximal jejunal branch artery of the cranial mesenteric artery was achieved in all subjects. Radiopaque microspheres and post-delivery angiographic evidence of stasis in the targeted vessels were observed on fluoroscopy after delivery of embolics. Preserved blood flow was observed after MSC delivery in the targeted vessel. The Chiu/Park score for intestinal ischemia in the targeted proximal jejunal segments were similar for microspheres (4, 4; n = 2) and MSCs (4, 4, 4, 3; n = 4), indicating moderate ischemic effects that were greater than for control duodenal tissue (3, 1; 0, 0, 3, 3).

CONCLUSIONS

Selective arteriographic deployment of MSCs in swine is feasible for study of directed intestinal stem cell delivery. In this study, directed therapy resulted in intestinal ischemia.

摘要

目的

评估在猪模型中经导管向小肠道内靶向输送人间质干细胞(MSCs)的可行性。

材料与方法

在切开颈动脉并引导下,对 6 头尤卡坦小型猪的头肠系膜动脉进行选择性导管插入术。对近端空肠分支动脉进行选择性导管插入术,以定向输送栓塞微球(100-300μm)或 MSCs(0.1-1000 万个细胞)。在 4 小时后处死猪,并从近端十二指肠和靶向空肠段采集标本。采用 Chiu/Park 系统对空肠和十二指肠的苏木精和伊红染色切片进行评分,以比较肠道缺血情况。

结果

所有研究对象均成功地将微球或 MSCs 输送到头肠系膜动脉的近端空肠分支动脉中。在输送栓塞剂后,透视检查观察到微球在靶向血管中具有不透射线性,并观察到滞留的血管造影证据。在靶向血管中输送 MSCs 后观察到保留的血流。靶向近端空肠段的肠道缺血 Chiu/Park 评分,微球组(4、4;n=2)和 MSC 组(4、4、4、3;n=4)相似,表明中度缺血效应大于对照组十二指肠组织(3、1;0、0、3、3)。

结论

猪选择性血管造影术输送 MSCs 是可行的,可用于研究定向肠道干细胞输送。在这项研究中,定向治疗导致了肠道缺血。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/9a0810b6c87d/nihms-1523391-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/b938682dfdb5/nihms-1523391-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/a7b25d330d91/nihms-1523391-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/5cd89ef27618/nihms-1523391-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/a96896830f1b/nihms-1523391-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/9a0810b6c87d/nihms-1523391-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/b938682dfdb5/nihms-1523391-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/a7b25d330d91/nihms-1523391-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/5cd89ef27618/nihms-1523391-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/a96896830f1b/nihms-1523391-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cf1/6589393/9a0810b6c87d/nihms-1523391-f0005.jpg

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