Culturing of Cardiac Cells in 3D Spheroids Modulates Their Expression Profile and Increases Secretion of Proangiogenic Growth Factors

Vasilets, Yu. D.; Дергилев, К. В.; Цоколаева, З. И.; Парфенова, Е. В.

doi:10.1007/s10517-022-05525-z

Cited by 5 publications

(2 citation statements)

References 12 publications

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“…Similar metabolic changes are also evident in 3D colorectal cancer cells when compared to 2D [22]. The inclusion of these processes in the data verifies numerous studies where 3D cells have been shown to express more biological relevance to in vivo systems than 2D cell cultures through the expression of pathways typically associated with in vivo environments [22,[46][47][48].…”

Section: Discussionsupporting

confidence: 73%

Transcriptional Landscape of 3D vs. 2D Ovarian Cancer Cell Models

Kerslake

Belay

Panfilov

et al. 2023

Cancers

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Three-dimensional (3D) cancer models are revolutionising research, allowing for the recapitulation of an in vivo-like response through the use of an in vitro system, which is more complex and physiologically relevant than traditional monolayer cultures. Cancers such as ovarian (OvCa) are prone to developing resistance, are often lethal, and stand to benefit greatly from the enhanced modelling emulated by 3D cultures. However, the current models often fall short of the predicted response, where reproducibility is limited owing to the lack of standardised methodology and established protocols. This meta-analysis aims to assess the current scope of 3D OvCa models and the differences in the genetic profiles presented by a vast array of 3D cultures. An analysis of the literature (Pubmed.gov) spanning 2012–2022 was used to identify studies with paired data of 3D and 2D monolayer counterparts in addition to RNA sequencing and microarray data. From the data, 19 cell lines were found to show differential regulation in their gene expression profiles depending on the bio-scaffold (i.e., agarose, collagen, or Matrigel) compared to 2D cell cultures. The top genes differentially expressed in 2D vs. 3D included C3, CXCL1, 2, and 8, IL1B, SLP1, FN1, IL6, DDIT4, PI3, LAMC2, CCL20, MMP1, IFI27, CFB, and ANGPTL4. The top enriched gene sets for 2D vs. 3D included IFN-α and IFN-γ response, TNF-α signalling, IL-6-JAK-STAT3 signalling, angiogenesis, hedgehog signalling, apoptosis, epithelial–mesenchymal transition, hypoxia, and inflammatory response. Our transversal comparison of numerous scaffolds allowed us to highlight the variability that can be induced by these scaffolds in the transcriptional landscape and identify key genes and biological processes that are hallmarks of cancer cells grown in 3D cultures. Future studies are needed to identify which is the most appropriate in vitro/preclinical model to study tumour microenvironments.

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Section: Discussionsupporting

confidence: 73%

Transcriptional Landscape of 3D vs. 2D Ovarian Cancer Cell Models

Kerslake

Belay

Panfilov

et al. 2023

Cancers

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“…Cardiosphere-derived cells (CDCs) are a promising cell type used for cell therapy [5,6]. CDCs are a combination of several progenitor cell populations derived from cultured myocardial explants that are cultured as 3D spheroids, resulting in the enhancement of their reparative properties [7][8][9]. Derived from spheroids, cardiosphere cells are capable of differentiating in cardiovascular lineages, but the key mechanism of their action is paracrine secretion of factors that can stimulate angiogenesis and cardiomyocyte proliferation/survival in recipient tissue [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor-Alpha Induces Proangiogenic Profiling of Cardiosphere-Derived Cell Secretome and Increases Its Ability to Stimulate Angiogenic Properties of Endothelial Cells

Dergilev,

Zubkova,

Guseva

et al. 2023

IJMS

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Ischemic heart disease and its complications, such as myocardial infarction and heart failure, are the leading causes of death in modern society. The adult heart innately lacks the capacity to regenerate the damaged myocardium after ischemic injury. Multiple lines of evidence indicated that stem-cell-based transplantation is one of the most promising treatments for damaged myocardial tissue. Different kinds of stem cells have their advantages for treating ischemic heart disease. One facet of their mechanism is the paracrine effect of the transplanted cells. Particularly promising are stem cells derived from cardiac tissue per se, referred to as cardiosphere-derived cells (CDCs), whose therapeutic effect is mediated by the paracrine mechanism through secretion of multiple bioactive molecules providing immunomodulatory, angiogenic, anti-fibrotic, and anti-inflammatory effects. Although secretome-based therapies are increasingly being used to treat various cardiac pathologies, many obstacles remain because of population heterogeneity, insufficient understanding of potential modulating compounds, and the principles of secretome regulation, which greatly limit the feasibility of this technology. In addition, components of the inflammatory microenvironment in ischemic myocardium may influence the secretome content of transplanted CDCs, thus altering the efficacy of cell therapy. In this work, we studied how Tumor necrosis factor alpha (TNFa), as a key component of the pro-inflammatory microenvironment in damaged myocardium from ischemic injury and heart failure, may affect the secretome content of CDCs and their angiogenic properties. We have shown for the first time that TNFa may act as a promising compound modulating the CDC secretome, which induces its profiling to enhance proangiogenic effects on endothelial cells. These results allow us to elucidate the underlying mechanisms of the impact of the inflammatory microenvironment on transplanted CDCs and may contribute to the optimization of CDC efficiency and the development of the technology for producing the CDC secretome with enhanced proangiogenic properties for cell-free therapy.

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