Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma

Song, Yeonhwa; Kim, Jin-Sun; Kim, Se-Hyuk; Park, Yoon Kyung; Yu, Eunsil; Kim, Ki‐Hun; Seo, Eul‐Ju; Oh, Heung‐Bum; Lee, Han Chu; Kim, Kang Mo; Seo, Haeng Ran

doi:10.1186/s13046-018-0752-0

Cited by 52 publications

(45 citation statements)

References 29 publications

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“…25–27 Moreover, primary cells isolated from patients cultured in 3D could maintain some special characteristics of cells in vivo for a long time in vitro. 9 All these findings imply that the response of 3D-cultured cells to antitumor drugs could better reflect the response of cells in vivo.…”

Section: Discussionmentioning

confidence: 96%

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool

Liao

Wang

et al. 2019

J Tissue Eng

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Spheroid culture is a widely used three-dimensional culture technology that simulates the three-dimensional structure of tumors in vivo and has been considered a good model for tumor research. However, current commercialized spheroid culture tools have the shortcomings of high cost or relatively poor spheroid-forming results for some special cells. To solve such problems, we designed a 3D printed, reusable, stamp-like resin mold that could shape microstructures for spheroid culture of tumor cells on the surface of agarose substrate in a 96-well plate. We applied this homemade three-dimensional culture tool in spheroid formation for hepatocellular carcinoma cells. The experimental data show that the effect of spheroid culture on four hepatocellular carcinoma cell lines in our homemade spheroid culture plate is better than that of the commercialized ultralow attachment spheroid culture plate, and compared to two-dimensional culture, three-dimensional culture improves cell functions. In addition, the drug-sensitive test based on patient-derived hepatocellular carcinoma cells showed a different pattern between spheroid and two-dimensional cultures. In conclusion, our spheroid culture tool is characterized by its low cost, reusability, low cell consumption, convenience in medium exchange, and good effect of spheroid formation, suggesting that this technique could be widely used in individual treatment and high-throughput drug screening.

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Section: Discussionmentioning

confidence: 96%

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool

Liao

Wang

et al. 2019

J Tissue Eng

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“…To address these issues, 3D cell culture models are a reliable alternative, providing experimentally accessible human models to study the biological processes of cancer. Several 3D culture platforms such as spheroids, organoids, hydrogels, 3D scaffolds, 3D bio-printing, and microfluidics have attempted the recreation of certain aspects of tumor microenvironments present in tissues including the brain [30][31][32][33][34][35][36], breast [37][38][39][40][41][42][43], ovarian [44][45][46][47][48][49][50][51], bone [52][53][54][55][56][57][58], liver [59][60][61][62][63][64][65], lung [66][67][68][69][70][71][72], colon [73][74][75][76]…”

Section: Mimicking Tme In Three-dimensionsmentioning

confidence: 99%

Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models

Bhattacharya

Calar

Puente

2020

J Exp Clin Cancer Res

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The heterogeneous tumor microenvironment (TME) is highly complex and not entirely understood. These complex configurations lead to the generation of oxygen-deprived conditions within the tumor niche, which modulate several intrinsic TME elements to promote immunosuppressive outcomes. Decoding these communications is necessary for designing effective therapeutic strategies that can effectively reduce tumor-associated chemotherapy resistance by employing the inherent potential of the immune system. While classic two-dimensional in vitro research models reveal critical hypoxia-driven biochemical cues, threedimensional (3D) cell culture models more accurately replicate the TME-immune manifestations. In this study, we review various 3D cell culture models currently being utilized to foster an oxygen-deprived TME, those that assess the dynamics associated with TME-immune cell penetrability within the tumor-like spatial structure, and discuss state of the art 3D systems that attempt recreating hypoxia-driven TME-immune outcomes. We also highlight the importance of integrating various hallmarks, which collectively might influence the functionality of these 3D models. This review strives to supplement perspectives to the quickly-evolving discipline that endeavors to mimic tumor hypoxia and tumor-immune interactions using 3D in vitro models.

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“…In order to devise 3D systems that more accurately reflect the molecular diversity of tumors and their respective TME, there was a need for protocols to promote the growth of spheroids and/or tumor organoids derived from cancer biopsies from patients (Song et al, 2018; Vlachogiannis et al, 2018). These patient derived tumor organoids are capable to recapitulate the molecular profile of the patients' tumors and have become a valuable platform for HTS of compounds and for personalization of therapy (van de Wetering et al, 2015; Vlachogiannis et al, 2018).…”

Section: Modeling the Tmementioning

confidence: 99%

Nanotheranostics Targeting the Tumor Microenvironment

Roma‐Rodrigues

Pombo

Raposo

et al. 2019

Front. Bioeng. Biotechnol.

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Cancer is considered the most aggressive malignancy to humans, and definitely the major cause of death worldwide. Despite the different and heterogenous presentation of the disease, there are pivotal cell elements involved in proliferation, differentiation, and immortalization, and ultimately the capability to evade treatment strategies. This is of utmost relevance when we are just beginning to grasp the complexity of the tumor environment and the molecular “evolution” within. The tumor micro-environment (TME) is thought to provide for differentiation niches for clonal development that results in tremendous cancer heterogeneity. To date, conventional cancer therapeutic strategies against cancer are failing to tackle the intricate interplay of actors within the TME. Nanomedicine has been proposing innovative strategies to tackle this TME and the cancer cells that simultaneously provide for biodistribution and/or assessment of action. These nanotheranostics systems are usually multi-functional nanosystems capable to carry and deliver active cargo to the site of interest and provide diagnostics capability, enabling early detection, and destruction of cancer cells in a more selective way. Some of the most promising multifunctional nanosystems are based on gold nanoparticles, whose physic-chemical properties have prompt for the development of multifunctional, responsive nanomedicines suitable for combinatory therapy and theranostics. Herein, we shall focus on the recent developments relying on the properties of gold nanoparticles as the basis for nanotheranostics systems against the heterogeneity within the TME.

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Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma

Cited by 52 publications

References 29 publications

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool

Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models

Nanotheranostics Targeting the Tumor Microenvironment

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