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Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT.
Stem Cell Research & Therapy ( IF 7.5 ) Pub Date : 2020-06-26 , DOI: 10.1186/s13287-020-01770-z
P Stephen Patrick 1 , Krishna K Kolluri 2 , May Zaw Thin 1 , Adam Edwards 2 , Elizabeth K Sage 2 , Tom Sanderson 3 , Benjamin D Weil 4 , John C Dickson 3 , Mark F Lythgoe 1 , Mark Lowdell 4, 5 , Sam M Janes 2 , Tammy L Kalber 1
Affiliation  

MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma. MSCTRAIL were radiolabelled with 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo. MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was amount- and time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections. 89Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.

中文翻译:

使用 89Zr-oxine PET-CT 可视化表达抗癌蛋白 TRAIL 的 MSC 的肺递送。

MSCTRAIL 是一种基于细胞的疗法,由经过基因改造的人同种异体脐带来源的 MSC 组成,可表达抗癌蛋白 TRAIL。尽管基于细胞的疗法通常在设计时考虑到目标组织,但由于缺乏可转化的非侵入性成像方法,很少对治疗进行评估。在这项临床前研究中,我们证明 89Zr-oxine 标记和 PET-CT 成像是非侵入性跟踪 MSCTRAIL 生物分布的潜在临床解决方案。这项技术的未来实施应该会提高我们在评估 MSCTRAIL 作为转移性肺腺癌治疗方法时的理解。MSCTRAIL 用 89Zr-oxine 进行放射性标记,并在标记后测定活力、表型和治疗效果。静脉注射后,在肺癌小鼠模型中对 89Zr-oxine 标记的 MSCTRAIL 进行 PET-CT 成像,并在体外证实了生物分布。MSCTRAIL 在体外保留了治疗功效和 MSC 表型,标记量达到或高于临床成像所需的量。89Zr-oxine 标记对细胞增殖率的影响是数量和时间依赖性的。PET-CT 成像显示,注射后 1 周内 MSCTRAIL 已递送至肺癌小鼠模型的肺部,并通过体内生物发光成像、放射自显影和组织切片荧光成像进行验证。89Zr-oxine 标记和 PET-CT 成像提供了一种评估新细胞疗法(包括 MSCTRAIL)在患者体内生物分布的潜在方法。这有助于增进对细胞疗法的理解,包括作用机制、迁移动力学和患者间变异性。
更新日期:2020-06-26
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