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VX2兔模型中的跨血管壁细胞移植、植入及肿瘤通路

Trans-Vessel Wall Cell Transplantation, Engraftment, and Tumor Access in the VX2 Rabbit Model.

作者信息

Lövljung Victoria, Waldén Mathias, Sandell Mikael, Damberg Peter, Holmin Staffan, Arnberg Sandor Fabian

机构信息

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Cell Transplant. 2025 Jan-Dec;34:9636897251313678. doi: 10.1177/09636897251313678.

Abstract

The trans-vessel wall device (TW-device) is a new endovascular tool for precise and safe delivery of various payloads (cells, viral, modified RNA, chemotherapy, growth factors) in oncology and regenerative medicine. The twofold aim of this study was to assess cell engraftment and tumor growth using the TW-device for endovascular transplantation and to evaluate its ability to directly access solid tumors. We used the VX2 model in the rabbit kidney to compare percutaneously implanted fresh VX2 cells with TW-device injections of cryopreserved VX2 cells. We demonstrated the feasibility of endovascular transplantation ( = 7) of tumor cells, achieving a 57.1% engraftment rate despite cryopreservation, comparable with 70% for percutaneous delivery of fresh cells ( = 10). Re-access using the TW-device was 100% successful ( = 11) with super-selective intratumoral contrast administration without complications. In conclusion, endovascular transplantation of VX2 cells using the TW-device resulted in proliferating cell grafts in the rabbit kidney establishing functional proof that cells indeed survive handling, preparation, and device passage. We also show the TW-device is able to access solid tumor parenchyma allowing precise intraparenchymal administration.This proof-of-concept study open up possibilities for repeated direct parenchymal injections via the endovascular route in any hard to reach organ.

摘要

跨血管壁装置(TW装置)是一种新型血管内工具,用于在肿瘤学和再生医学中精确、安全地递送各种负载物(细胞、病毒、修饰RNA、化疗药物、生长因子)。本研究的双重目的是使用TW装置进行血管内移植来评估细胞植入和肿瘤生长,并评估其直接进入实体瘤的能力。我们使用兔肾VX2模型,将经皮植入的新鲜VX2细胞与通过TW装置注射的冷冻保存的VX2细胞进行比较。我们证明了肿瘤细胞血管内移植(n = 7)的可行性,尽管进行了冷冻保存,但植入率仍达到57.1%,与经皮递送新鲜细胞的70%(n = 10)相当。使用TW装置再次进入肿瘤100%成功(n = 11),可进行超选择性瘤内造影剂给药且无并发症。总之,使用TW装置进行VX2细胞的血管内移植导致兔肾中的细胞移植物增殖,从功能上证明细胞确实能在处理、制备和通过装置的过程中存活。我们还表明,TW装置能够进入实体瘤实质,允许进行精确的实质内给药。这项概念验证研究为通过血管内途径在任何难以到达的器官中重复进行直接实质内注射开辟了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/423d/11773539/44bbf3ab234d/10.1177_09636897251313678-img2.jpg

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