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肝切除术后利用切除的伴有肝细胞癌或胆管癌的器官进行肝细胞移植的新策略。

Novel strategy for hepatocyte transplantation using resected organ with hepatocellular carcinoma or cholangiocarcinoma after hepatectomy.

作者信息

Kawai Toki, Ito Masahiro, Hayashi Chihiro, Yamamoto Naoki, Asano Yukio, Arakawa Satoshi, Horiguchi Akihiko

机构信息

Department of Gastroenterological Surgery, Fujita Health University Bantane Hospital, Nagoya, Aichi, Japan.

Fujita Health University, Institute for Comprehensive Medical Science, Toyoake, Aichi, Japan.

出版信息

Fujita Med J. 2020;6(1):7-11. doi: 10.20407/fmj.2019-009. Epub 2019 Nov 2.

Abstract

OBJECTIVES

Although large hepatectomy (i.e., resection of 2-3 segments) is an increasingly common treatment for hepatocellular carcinoma and cholangiocarcinoma, it can lead to liver failure. However, a resected liver may contain large quantities of both normal hepatocytes (NHs) and carcinoma cells. We investigated separating these cell types so that NHs could be used as transplantable cells.

MATERIALS AND METHODS

Cancer cells were developed by immortalizing rat hepatocytes, using an artificial chromosome vector. Cancer cells and primary hepatocytes (PHs) were mixed in a 1:1 ratio, then separated into two groups using fluorescence activated cell sorting (FACS). Normal hepatocytes after FACS (NHaF) and cancer cells after FACS (CAaF) were transplanted into two spots on opposite sides of the backs of nude mice; and also into the spleens of three groups (NHaF, CAaF and controls) of non-albumin rats (NARs), from which we measured blood albumin levels, using ELISA.

RESULT

The PH and cancer cells were successfully separated using FACS. After separation, cancer cells transplanted subcutaneously in nude mice formed tumors, whereas transplanted PH cells in NARs only produced higher albumin levels.

CONCLUSION

Transplanted NHaF cells did not produce tumors. However, this cells function was not enough in power for transplant source by this method. Nevertheless, we believe this technique can be improved and used to treat patients successfully.

摘要

目的

尽管大肝切除术(即切除2 - 3个肝段)是肝细胞癌和胆管癌越来越常用的治疗方法,但它可能导致肝衰竭。然而,切除的肝脏可能同时含有大量正常肝细胞(NHs)和癌细胞。我们研究了分离这些细胞类型,以便将正常肝细胞用作可移植细胞。

材料与方法

使用人工染色体载体使大鼠肝细胞永生化来培养癌细胞。将癌细胞和原代肝细胞(PHs)按1:1的比例混合,然后使用荧光激活细胞分选(FACS)将其分为两组。将FACS后的正常肝细胞(NHaF)和FACS后的癌细胞(CAaF)分别移植到裸鼠背部相对两侧的两个部位;同时也移植到三组非白蛋白大鼠(NARs)(NHaF组、CAaF组和对照组)的脾脏中,我们使用酶联免疫吸附测定(ELISA)法测量其血白蛋白水平。

结果

使用FACS成功分离了原代肝细胞和癌细胞。分离后,皮下移植到裸鼠体内的癌细胞形成了肿瘤,而移植到非白蛋白大鼠体内的原代肝细胞仅使白蛋白水平升高。

结论

移植的NHaF细胞未产生肿瘤。然而,通过这种方法,这种细胞的功能作为移植来源还不够强大。尽管如此,我们相信这项技术可以改进并成功用于治疗患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f2/8766655/1d5a14cfa059/fmj-6-007-g001.jpg

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