Dataset Information

Electrochemical mapping of oxygenation in the three-dimensional multicellular tumour hemi-spheroid.

ABSTRACT: Blood capillaries deliver oxygen and nutrients to surrounding micro-regions of tissue and carry away metabolic waste. In normal tissue, capillaries are close enough to keep all the cells viable. In solid tumours, the capillary system is chaotic and typical inter-capillary distances are larger than in normal tissue. Therefore, hypoxic regions develop. Drug molecules may not reach these areas at concentrations above the lethal level. The combined effect of low drug concentrations and local hypoxia, often exacerbated by acidity, leads to therapy failure. To better understand the interplay between hypoxia and poor drug penetration, oxygenation needs to be assessed in different areas of inter-capillary tissue. The multicellular tumour spheroid is a well-established three-dimensional (3D) in vitro model of the capillary microenvironment. It is used to mimic nascent tumours and micro-metastases as well. In this work, we demonstrate for the first time that dynamic intra-spheroidal oxygen maps can be obtained at the 3D multicellular tumour hemi-spheroid (MCH) using a non-invasive microelectrode array. The same oxygen distributions exist inside the equivalent but less accessible full spheroid. The MCH makes high throughput-high content analysis of spheroids feasible and thus can assist studies on basic cancer biology, drug development and personalized medicine.

SUBMITTER: Sheth DB

PROVIDER: S-EPMC6545061 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Electrochemical mapping of oxygenation in the three-dimensional multicellular tumour hemi-spheroid.

Sheth Disha B DB Gratzl Miklόs M

Proceedings. Mathematical, physical, and engineering sciences 20190522 2225

Blood capillaries deliver oxygen and nutrients to surrounding micro-regions of tissue and carry away metabolic waste. In normal tissue, capillaries are close enough to keep all the cells viable. In solid tumours, the capillary system is chaotic and typical inter-capillary distances are larger than in normal tissue. Therefore, hypoxic regions develop. Drug molecules may not reach these areas at concentrations above the lethal level. The combined effect of low drug concentrations and local hypoxia ...[more]

PMID: 31236040

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Project description:Background:Mass production of exosomes is a prerequisite for their commercial utilization. This study investigated whether three-dimensional (3D) spheroid culture of mesenchymal stem cells (MSCs) could improve the production efficiency of exosomes and if so, what was the mechanism involved. Methods:We adopted two models of 3D spheroid culture using the hanging-drop (3D-HD) and poly(2-hydroxyethyl methacrylate) (poly-HEMA) coating methods (3D-PH). The efficiency of exosome production from MSCs in the 3D spheroids was compared with that of monolayer culture in various conditions. We then investigated the mechanism of the 3D spheroid culture-induced increase in exosome production. Results:The 3D-HD formed a single larger spheroid, while the 3D-PH formed multiple smaller ones. However, MSCs cultured on both types of spheroids produced significantly more exosomes than those cultured in conventional monolayer culture (2D). We then investigated the cause of the increased exosome production in terms of hypoxia within the 3D spheroids, high cell density, and non-adherent cell morphology. With increasing spheroid size, the efficiency of exosome production was the largest with the least amount of cells in both 3D-HD and 3D-PH. An increase in cell density in 2D culture (2D-H) was less efficient in exosome production than the conventional, lower cell density, 2D culture. Finally, when cells were plated at normal density on the poly-HEMA coated spheroids (3D-N-PH); they formed small aggregates of less than 10 cells and still produced more exosomes than those in the 2D culture when plated at the same density. We also found that the expression of F-actin was markedly reduced in the 3D-N-PH culture. Conclusion:These results suggested that 3D spheroid culture produces more exosomes than 2D culture and the non-adherent round cell morphology itself might be a causative factor. The result of the present study could provide useful information to develop an optimal process for the mass production of exosomes.

Dataset Information

Electrochemical mapping of oxygenation in the three-dimensional multicellular tumour hemi-spheroid.

Publications

Electrochemical mapping of oxygenation in the three-dimensional multicellular tumour hemi-spheroid.

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