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子宫肌层、平滑肌瘤和平滑肌肉瘤细胞三维培养的建立:两种不同模型的优缺点

Establishment of 3D Cultures of Myometrium, Leiomyoma, and Leiomyosarcoma Cells: Advantages and Disadvantages of Two Different Models.

作者信息

Pellegrino Pamela, Greco Stefania, Duménigo Gonzàlez Abel, Giampieri Francesca, Giannubilo Stefano Raffaele, Delli Carpini Giovanni, Capocasa Franco, Mezzetti Bruno, Battino Maurizio, Ciavattini Andrea, Ciarmela Pasquapina

机构信息

Department of Experimental and Clinical Medicine, Faculty of Medicine, Università Politecnica Delle Marche, Via Tronto 10/a, 60020, Ancona, Italy.

Department of Clinical Science, Università Politecnica Delle Marche, Ancona, Italy.

出版信息

Reprod Sci. 2024 Dec;31(12):3729-3742. doi: 10.1007/s43032-024-01724-3. Epub 2024 Nov 5.

DOI:10.1007/s43032-024-01724-3
PMID:39500848
Abstract

Uterine leiomyomas are the most common benign, monoclonal, gynaecological tumors in a woman's uterus, while leiomyosarcoma is a rare but aggressive condition caused by the malignant transformation of the myometrium. To overcome the common obstacles related to the methods usually used to study these pathologies, we aimed to devise three-dimensional models of myometrium, uterine leiomyoma and leiomyosarcoma cell lines, using two different types of biocompatible scaffolds. Specifically, we exploited the agarose gel matrix in common 6-well plates and the alginate matrix using Bioprinting INKREDIBLE + (CELLINK), a pneumatic extruded base equipped with a system with double printheads, and a UV printer LED curing system. Both methods allowed the development of 3D spheroids of all three cell types, that were also suitable for morphological investigations. We showed that all cell types embedded in both agarose and alginate formed spheroids in their growth medium. The spheroids successfully proliferated and self-organized into complex structures, developing a sustainable system that emulated the condition of the tissues through the accumulation of extracellular matrix. These models could be useful for a better understanding of pathophysiology, etiopathogenesis, and testing new methods or molecules from a preventive and therapeutic point of view.

摘要

子宫平滑肌瘤是女性子宫中最常见的良性单克隆妇科肿瘤,而平滑肌肉瘤则是一种罕见但侵袭性强的疾病,由子宫肌层的恶性转化引起。为了克服与通常用于研究这些病理状况的方法相关的常见障碍,我们旨在使用两种不同类型的生物相容性支架设计子宫肌层、子宫平滑肌瘤和平滑肌肉瘤细胞系的三维模型。具体而言,我们利用普通6孔板中的琼脂糖凝胶基质以及使用Bioprinting INKREDIBLE +(CELLINK)的藻酸盐基质,这是一种配备双打印头系统的气动挤出底座和紫外线打印机LED固化系统。两种方法都能培养出所有三种细胞类型的三维球体,这些球体也适用于形态学研究。我们发现,嵌入琼脂糖和藻酸盐中的所有细胞类型在其生长培养基中都能形成球体。这些球体成功增殖并自组织成复杂结构,通过细胞外基质的积累形成了一个模拟组织状况的可持续系统。从预防和治疗的角度来看,这些模型可能有助于更好地理解病理生理学、病因发病机制以及测试新的方法或分子。

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Establishment of 3D Cultures of Myometrium, Leiomyoma, and Leiomyosarcoma Cells: Advantages and Disadvantages of Two Different Models.子宫肌层、平滑肌瘤和平滑肌肉瘤细胞三维培养的建立:两种不同模型的优缺点
Reprod Sci. 2024 Dec;31(12):3729-3742. doi: 10.1007/s43032-024-01724-3. Epub 2024 Nov 5.
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引用本文的文献

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Three-Dimensional Bioprinting and Infertility-Related Female Reproductive System Diseases: A Review of Current and Future Applications.三维生物打印与不孕症相关的女性生殖系统疾病:当前及未来应用综述
Tissue Eng Regen Med. 2025 Aug 19. doi: 10.1007/s13770-025-00754-5.

本文引用的文献

1
Current status and challenges in uterine myometrial tissue engineering.子宫肌层组织工程的现状与挑战。
Bioengineered. 2023 Dec;14(1):2251847. doi: 10.1080/21655979.2023.2251847.
2
The In Vitro Effects of Romina Strawberry Extract on 3D Uterine Leiomyosarcoma Cells.罗米娜草莓提取物对 3D 子宫平滑肌肉瘤细胞的体外影响。
Nutrients. 2023 May 30;15(11):2557. doi: 10.3390/nu15112557.
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Human Myometrial and Uterine Fibroid Stem Cell-Derived Organoids for Intervening the Pathophysiology of Uterine Fibroid.用于干预子宫肌瘤病理生理学的人子宫肌层和子宫肌瘤干细胞衍生类器官
Reprod Sci. 2022 Sep;29(9):2607-2619. doi: 10.1007/s43032-022-00960-9. Epub 2022 May 18.
4
3D Models of Cellular Spheroids As a Universal Tool for Studying the Cytotoxic Properties of Anticancer Compounds In Vitro.细胞球体的3D模型作为体外研究抗癌化合物细胞毒性特性的通用工具。
Acta Naturae. 2022 Jan-Mar;14(1):92-100. doi: 10.32607/actanaturae.11603.
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Development of Primary Monolayer Cell Model and Organotypic Model of Uterine Leiomyoma.子宫平滑肌瘤原代单层细胞模型和器官型模型的建立。
Methods Protoc. 2022 Feb 6;5(1):16. doi: 10.3390/mps5010016.
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Uterine fibroid vascularization: from morphological evidence to clinical implications.子宫肌瘤血管生成:从形态学证据到临床意义
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Macrophages and Immune Responses in Uterine Fibroids.子宫肌瘤中的巨噬细胞与免疫应答。
Cells. 2021 Apr 22;10(5):982. doi: 10.3390/cells10050982.
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A Review on the Adaption of Alginate-Gelatin Hydrogels for 3D Cultures and Bioprinting.藻酸盐-明胶水凝胶用于3D培养和生物打印的适应性综述
Materials (Basel). 2021 Feb 10;14(4):858. doi: 10.3390/ma14040858.
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Physical traits of cancer.癌症的物理特征。
Science. 2020 Oct 30;370(6516). doi: 10.1126/science.aaz0868.
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Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy.肿瘤微环境中的细胞外基质及其对癌症治疗的影响。
Front Mol Biosci. 2020 Jan 31;6:160. doi: 10.3389/fmolb.2019.00160. eCollection 2019.