Organoids in Translational Oncology

Tatullo, Marco; Marrelli, Benedetta; Benincasa, Caterina; Aiello, Elisabetta; Makeeva, Irina; Zavan, Barbara; Ballini, Andrea; Vito, Danila De; Spagnuolo, Gianrico

doi:10.3390/jcm9092774

Cited by 25 publications

(18 citation statements)

References 78 publications

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“…3D culture methods have been used extensively to study cancer biology in multiple cancer types, ultimately revealing novel insights into cancer-related fields such as hypoxia and angiogenesis, invasion and metastases, drug screening, mutagenesis, and more [ 17 , 22 , 23 , 24 , 25 , 26 , 27 ]. In this review we will focus on how researchers have used 3D culture systems to advance our understanding of cancer immunology and immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

3D Culture Systems for Exploring Cancer Immunology

Fitzgerald

Weiner

2020

Cancers

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Cancer immunotherapy has revolutionized cancer treatment, spurring extensive investigation into cancer immunology and how to exploit this biology for therapeutic benefit. Current methods to investigate cancer-immune cell interactions and develop novel drug therapies rely on either two-dimensional (2D) culture systems or murine models. However, three-dimensional (3D) culture systems provide a potentially superior alternative model to both 2D and murine approaches. As opposed to 2D models, 3D models are more physiologically relevant and better replicate tumor complexities. Compared to murine models, 3D models are cheaper, faster, and can study the human immune system. In this review, we discuss the most common 3D culture systems—spheroids, organoids, and microfluidic chips—and detail how these systems have advanced our understanding of cancer immunology.

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Section: Introductionmentioning

confidence: 99%

3D Culture Systems for Exploring Cancer Immunology

Fitzgerald

Weiner

2020

Cancers

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“…The in vitro 3D cultures derived from patients' cancer cells (i.e. tumoroids) have been introduced to modern cancer investigation [13,[107][108][109]. These cultures maintain the heterogeneity and complexity of their parental tumours to some extent, which makes them reliable cancer tissue models [110][111][112][113][114].…”

Section: Patient-derived Tumoroidsmentioning

confidence: 99%

“…The 3D cultures can be established using different methods, including hanging drops, hydrogels, low-attachment microtiter plates and scaffolds [7][8][9][10]. In recent decades, in vitro 3D cultures derived from animal and human cells have been a cornerstone in investigations of cell biology, translational medicine and drug design [11][12][13][14][15]. Furthermore, 3D cultures provide a closer view to the in vivo physiology of the cells [16,17].…”

Section: Introduction In Vitro 3d Culturesmentioning

confidence: 99%

Characterization of in vitro 3D cultures

Mousavi

2021

APMIS

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SummaryOver the past decade, 3D culture models of human and animal cells have found their way into tissue differentiation, drug development, personalized medicine and tumour behaviour studies. Embryoid bodies (EBs) are in vitro 3D cultures established from murine pluripotential stem cells, whereas tumoroids are patient‐derived in vitro 3D cultures. This thesis aims to describe a new implication of an embryoid body model and to characterize the patient‐specific microenvironment of the parental tumour in relation to tumoroid growth rate. In this thesis, we described a high‐throughput monitoring method, where EBs are used as a dynamic angiogenesis model. In this model, digital image analysis (DIA) is implemented on immunohistochemistry (IHC) stained sections of the cultures over time. Furthermore, we have investigated the correlation between the genetic profile and inflammatory microenvironment of parental tumours on the in vitro growth rate of tumoroids. The EBs were cultured in spinner flasks. The samples were collected at days 4, 6, 9, 14, 18 and 21, dehydrated and embedded in paraffin. The histological sections were IHC stained for the endothelial marker CD31 and digitally scanned. The virtual whole‐image slides were digitally analysed by Visiopharm® software. Histological evaluation showed vascular‐like structures over time. The quantitative DIA was plausible to monitor significant increase in the total area of the EBs and an increase in endothelial differentiation. The tumoroids were established from 32 colorectal adenocarcinomas. The in vitro growth rate of the tumoroids was followed by automated microscopy over an 11‐day period. The parental tumours were analysed by next‐generation sequencing for KRAS, TP53, PIK3CA, SMAD4, MAP2K1, BRAF, FGFR3 and FBXW7 status. The tumoroids established from KRAS‐mutated parental tumours showed a significantly higher growth rate compared to their wild‐type counterparts. The density of CD3+ T lymphocytes and CD68+ macrophages was calculated in the centre of the tumours and at the invasive margin of the tumours. The high density of CD3+ cells and the low density of CD68+ cells showed a significant correlation with a higher growth rate of the tumoroids. In conclusion, a novel approach for histological monitoring of endothelial differentiation is presented in the stem cell‐derived EBs. Furthermore, the KRAS status and density of CD3+ T cells and macrophages in the parental tumour influence the growth rate of the tumoroids. Our results indicate that these parameters should be included when tumoroids are to be implemented in personalized medicine

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“…A total of 8 papers were published, including a single review and seven original articles. Firstly, “Organoids and Tumoroids” are growing approaches in oncology [ 1 , 2 ] and are reviewed in this issue [ 3 ]. Secondly, “Saliva Biopsy” is a minimally invasive liquid biopsy compatible with oral and systemic status.…”

Section: A Special Issue Of Oral Cancersmentioning

confidence: 99%

“…Tumoroids a.k.a. tumor organoids were reviewed by Tatullo et al with 77 references [ 3 ]. The scientific research on cancer biology was based on in vitro experiments, carried out on tissue culture plates and two-dimensional (2D) samples.…”

Section: Tumoroids and Organoidsmentioning

confidence: 99%