Establishment of Organoids From Human Epithelioid Sarcoma With the Air-Liquid Interface Organoid Cultures.
Establishment of Organoids From Human Epithelioid Sarcoma With the Air-Liquid Interface Organoid Cultures.
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DOI：
10.3389/fonc.2022.893592
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发表时间：
2022
影响因子：
4.7
通讯作者：
Takenaka, Satoshi
中科院分区：
文献类型：
--
作者：
Wakamatsu, Toru;Ogawa, Hisataka;Yoshida, Keiichi;Matsuoka, Yukiko;Shizuma, Kazuko;Imura, Yoshinori;Tamiya, Hironari;Nakai, Sho;Yagi, Toshinari;Nagata, Shigenori;Yui, Yoshihiro;Sasagawa, Satoru;Takenaka, Satoshi
关键词：
尽管生物资源对于肿瘤学领域的基础和临床前研究是必不可少的，但对于肉瘤的生物资源对于治疗的快速发展是不够的。到目前为止，已经建立了一些肉瘤细胞系，但是成功率很低，并且建立的肉瘤类型经常存在偏差。因此，需要一种有效的培养方法来确定各种类型的肉瘤。类器官培养是一种三维培养方法，能够再现肿瘤微环境，报道的成功率高于二维培养。本研究的目的是报道我们利用气液界面类器官培养方法从人上皮样肉瘤中新建立的类器官。我们治疗了2例上皮样肉瘤。手术切除后剩余肉瘤标本按照气液界面类器官培养法包埋于1型胶原凝胶中。在连续传代后，我们将类器官移植到NOD-scid IL2Rgnull （NSG）小鼠体内。利用已形成的肿瘤，我们进行了组织学和基因组分析，以比较其与患者原始上皮样肉瘤的异同。上皮样肉瘤的类器官可连续培养并在1型胶原凝胶中维持3代以上。在NSG小鼠中检测到已形成的原位肿瘤异种移植物。该过程多次重复后，从上皮样肉瘤中建立了患者衍生的类器官系。经聚合酶链反应和免疫组织化学分析，所建立的类器官显示整合酶相互作用1的表达缺失。上皮样肉瘤的异种移植类器官在组织学上具有与原肿瘤相似的表型，在遗传上也有一定程度的相似。本研究建立了2种新的上皮样肉瘤类器官模型，为研究上皮样肉瘤的分子发病机制和开发新的治疗方法提供了基础。
Although biological resources are essential for basic and preclinical research in the oncological field, those of sarcoma are not sufficient for rapid development of the treatment. So far, some sarcoma cell lines have been established, however, the success rate was low and the established sarcoma types were frequently biased. Therefore, an efficient culture method is needed to determine the various types of sarcomas. Organoid culture is a 3-dimentional culture method that enables the recapitulation of the tumor microenvironment and the success rate reported is higher than the 2-dimentional culture. The purpose of this study was to report our newly established organoids from human epithelioid sarcoma using the air-liquid interface organoid culture method. We treated 2 patients with epithelioid sarcoma in our institute. The remaining sarcoma specimens after surgical resection were embedded in collagen type 1 gels according to the air-liquid interface organoid culture method. After serial passages, we xenografted the organoids to NOD-scid IL2Rgnull (NSG) mice. Using the developed tumors, we performed histological and genomic analyses to compare the similarities and differences with the original epithelioid sarcoma from the patient. Organoids from the epithelioid sarcoma could be serially cultured and maintained in collagen type 1 gels for more than 3 passages. Developed orthotopic tumor xenografts were detected in the NSG mice. After the process was repeated severally, the patient derived organoid lines from the epithelioid sarcoma were established. The established organoids showed loss of integrase interactor 1 expression with polymerase chain reaction and immunohistochemical analyses. The xenografted organoids of the epithelioid sarcoma had histologically similar phenotypes with the original tumor and genetically resembled it to some degree. The present study demonstrated 2 novel established organoid models of epithelioid sarcoma, and our organoid models could be used to investigate the molecular pathogenesis and develop a novel treatment.
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DOI：
10.1038/s41578-021-00279-y
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hofer M;Lutolf MP
通讯作者：
Lutolf MP
影响因子：
1.8
作者：
Imura Y;Naka N;Outani H;Yasui H;Takenaka S;Hamada K;Ozaki R;Kaya M;Yoshida K;Morii E;Myoui A;Yoshikawa H
通讯作者：
Yoshikawa H
影响因子：
51.1
作者：
Gounder, Mrinal;Schoffski, Patrick;Stacchiotti, Silvia
通讯作者：
Stacchiotti, Silvia
影响因子：
64.5
作者：
Neal, James T.;Li, Xingnan;Kuo, Calvin J.
通讯作者：
Kuo, Calvin J.
影响因子：
16.6
作者：
Calandrini, Camilla;Schutgens, Frans;Drost, Jarno
通讯作者：
Drost, Jarno