Fused X-ray and MR imaging guidance of intrapericardial delivery of microencapsulated human mesenchymal stem cells in immunocompetent swine.

Fused X-ray and MR imaging guidance of intrapericardial delivery of microencapsulated human mesenchymal stem cells in immunocompetent swine.
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DOI:
10.1148/radiol.14131424
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发表时间:
2014-08
期刊:
影响因子:
19.7
通讯作者:
Kraitchman DL
Kraitchman DL
中科院分区:
医学1区
文献类型:
--
作者:
Fu Y;Azene N;Ehtiati T;Flammang A;Gilson WD;Gabrielson K;Weiss CR;Bulte JW;Solaiyappan M;Johnston PV;Kraitchman DL

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目的:评价微囊化异种人骨髓间充质干细胞(HMSCs)经微囊化、核磁共振(MR)引导下心包内移植治疗免疫功能猪模型中缺血性心血管疾病的可能性。所有动物实验都得到了机构动物护理和使用委员会的批准。采用改良的海藻酸盐-聚L-赖氨酸-海藻酸盐包埋法进行干细胞微胶囊化,将10%(wt/Vol)的硫酸钡包埋,制成含有人骨髓间充质干细胞的海藻酸钡微囊(BaCaps)。在X-射线/磁共振成像引导下,8头雌性猪(约25公斤)随机接受BaCaps、空BaCaps、裸hMSCs或生理盐水,采用经皮剑突下入路,并与仅使用标准透视分娩的空BaCaps(n=1)或BaCaps+hMSCs(n=2)进行比较。分别于注射前和产后1周采集MR图像和C臂CT图像。立即或1周后处死动物,进行组织病理学验证。用配对学生t检验评估基线和产后1周的心功能。HMSCs在体外包裹2天后仍有较高的存活率(94.8%±6)。通过x射线/磁共振成像,所有动物都成功地实现了心包内切开和分娩。产后即刻和产后1周,透视和C臂CT均可见BaCaps。虽然BaCaps在出生后立即自由漂浮,但在1周时它们巩固成假性心外膜组织块,hMSCs在BaCaps中仍然高度存活;裸露的hMSCs保留得很差。X线/MR引导下心包内分娩后1周随访未见心包粘连和/或渗出,对心功能无不良影响。与之不同的是,在X线透视下植入BaCaps的3例患者(n=3)在1周后出现心包粘连和hMSC活性降低。BaCaps与hMSCs经心包腔内注射可获得较高的细胞存留率和存活率。在X线/磁共振成像的引导下,心包内分娩可以在不存在心包积液的情况下安全地进行,为心脏细胞再生治疗提供了一条新的途径。
To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model. All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg) were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs, or saline by using a percutaneous subxiphoid approach and were compared with animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using standard fluoroscopic delivery only. MR images and C-arm computed tomographic (CT) images were acquired before injection and 1 week after delivery. Animals were sacrificed immediately or at 1 week for histopathologic validation. Cardiac function between baseline and 1 week after delivery was evaluated by using a paired Student t test. hMSCs remained highly viable (94.8% ± 6) 2 days after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial access and delivery were achieved in all animals. BaCaps were visible fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas BaCaps were free floating immediately after delivery, they consolidated into a pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x-ray/MR imaging–guided intrapericardial delivery showed no evidence of pericardial adhesion and/or effusion or adverse effect on cardiac function. In contradistinction, BaCaps delivery with xray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week. Intrapericardial delivery of BaCaps with hMSCs leads to high cell retention and survival. With x-ray/MR imaging guidance, intrapericardial delivery can be performed safely in the absence of preexisting pericardial effusion to provide a novel route for cardiac cellular regenerative therapy.
DOI: 10.1161/cir.0b013e31823ac046
发表时间: 2012-01-03
期刊: Circulation
影响因子: 37.8
作者:
Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者: American Heart Association Statistics Committee and Stroke Statistics Subcommittee
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发表时间: 2011
期刊: PloS one
影响因子: 3.7
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发表时间: 2005-05-03
期刊: CIRCULATION
影响因子: 37.8
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发表时间: 2012-06
期刊: STEM CELLS
影响因子: 5.2
作者:
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