A novel 3D heterotypic spheroid model for studying extracellular vesicle-mediated tumour and immune cell communication

Sadovska, Lilite; Zandberga, Elīna; Sagini, Krizia; Jēkabsons, Kaspars; Riekstiņa, Una; Kalniņa, Zane; Llorente, Alicia; Linē, Aija

doi:10.1016/j.bbrc.2017.12.072

Cited by 22 publications

(25 citation statements)

References 29 publications

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“…In the last few years, 3D in vitro models have been developed and tailored to better recapitulate the in vivo features of tumors. [50][51][52] Additionally, it is unclear whether 3D models provide an efficient and costeffective production of EVs as compared to 2D models. [46] Importantly, it has already been shown that some of these cellular features, such as differentiation [47] and phenotype, [48,49] affect the content and function of EVs.…”

Section: Introductionmentioning

confidence: 99%

3D Cellular Architecture Affects MicroRNA and Protein Cargo of Extracellular Vesicles

et al. 2018

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The success of malignant tumors is conditioned by the intercellular communication between tumor cells and their microenvironment, with extracellular vesicles (EVs) acting as main mediators. While the value of 3D conditions to study tumor cells is well established, the impact of cellular architecture on EV content and function is not investigated yet. Here, a recently developed 3D cell culture microwell array is adapted for EV production and a comprehensive comparative analysis of biochemical features, RNA and proteomic profiles of EVs secreted by 2D vs 3D cultures of gastric cancer cells, is performed. 3D cultures are significantly more efficient in producing EVs than 2D cultures. Global upregulation of microRNAs and downregulation of proteins in 3D are observed, indicating their dynamic coregulation in response to cellular architecture, with the ADP‐ribosylation factor 6 signaling pathway significantly downregulated in 3D EVs. The data strengthen the biological relevance of cellular architecture for production and cargo of EVs.

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Section: Introductionmentioning

confidence: 99%

3D Cellular Architecture Affects MicroRNA and Protein Cargo of Extracellular Vesicles

et al. 2018

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“…Consequently, it is important to purify exosomes to minimize contamination with lipoproteins and to use the appropriate controls to assess for artifactual uptake . For certain studies, these issues can be overcome through labeling of specific vesicles by transfecting the parent cells with a vesicle‐targeted fluorescent probe or reporter protein …”

Section: Methods To Identify and Characterize Exosomesmentioning

confidence: 99%

“…66 For certain studies, these issues can be overcome through labeling of specific vesicles by transfecting the parent cells with a vesicletargeted fluorescent probe or reporter protein. 67…”

Section: Methods To Identify and Characterize Exosomesmentioning

confidence: 99%

“…The contributions of different genetic backgrounds or gene mutations on exosome cargo and the resulting phenotypic effects of exosomes on recipient iPSC‐derived cells can also be studied using patient‐specific iPSCs. Furthermore, 3‐dimensional organoid models have been developed to investigate EV‐mediated intercellular communication . This model is based on coculturing recipient cells with donor cells containing a CD63–GFP reporter under control of a cell‐type–specific promoter.…”

Section: Ipscs As a Tool To Understand Intercellular Communication Inmentioning

confidence: 99%

“…Furthermore, 3-dimensional organoid models have been developed to investigate EV-mediated intercellular communication. 67 This model is based on coculturing recipient cells with donor cells containing a CD63-GFP reporter under control of a cell-type-specific promoter. In this manner, EV-mediated intercellular communication can be investigated under conditions closer to the physiological environment.…”

Section: Ipscs As a Tool To Understand Intercellular Communication Inmentioning

confidence: 99%

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Extracellular vesicles from organoids and 3D culture systems

Abdollahi

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When discovered, extracellular vesicles (EVs) such as exosomes were thought of as junk carriers and a means by which the cell disposed of its waste material. Over the years, the role of EVs in cell communication has become apparent with the discovery that the nano‐scale vesicles also transport RNA, DNA, and other bioactive components to and from the cells. These findings were originally made in EVs from body fluids of organisms and from in vitro two‐dimensional (2D) cell culture models. Recently, organoids and other 3D multicellular in vitro models are being used to study EVs in the context of both physiologic and pathological states. However, standard, reproducible methods are lacking for EV analysis using these models. As a step toward understanding the implications of these platforms, this review provides a comprehensive picture of the progress using 3D in vitro culture models for EV analysis. Translational efforts and regulatory considerations for EV therapeutics are also briefly overviewed to understand what is needed for scale‐up and, ultimately, commercialization.

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A novel 3D heterotypic spheroid model for studying extracellular vesicle-mediated tumour and immune cell communication

Cited by 22 publications

References 29 publications

3D Cellular Architecture Affects MicroRNA and Protein Cargo of Extracellular Vesicles

3D Cellular Architecture Affects MicroRNA and Protein Cargo of Extracellular Vesicles

Examining the Paracrine Effects of Exosomes in Cardiovascular Disease and Repair

Extracellular vesicles from organoids and 3D culture systems

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