Physiologically relevant culture medium Plasmax improves human placental trophoblast stem cell function

Avellino, Giulia; Deshmukh, Ruhi; Rogers, Stephanie N; Charnock‐Jones, D. Stephen; Smith, Gordon C. S.; Tardito, Saverio; Aye, Irving L.M.H.

doi:10.1152/ajpcell.00581.2022

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Despite the advancing understanding of environmental influences on metabolism, these traditional media continue to serve as the standard for in vitro studies across diverse biological research disciplines 21 . The emergence of physiologic media, along with other initiatives aimed at enhancing the modelling capabilities of cell culture 22 , harbours significant promise for advancing our understanding of fundamental cellular processes 5,[23][24][25] . This is particularly relevant in the context of the establishment of defined and robust culture conditions for iPSC and iPSC-differentiated cell types.…”

Section: Discussionmentioning

confidence: 99%

Physiologic media renders human iPSC-derived macrophages permissive forM. tuberculosisby rewiring organelle function and metabolism

Bussi,

Lai,

Athanasiade

et al. 2024

Preprint

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In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analysed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarisation. Functionally, we discovered that HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-differentiated macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function.

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Section: Discussionmentioning

confidence: 99%

Physiologic media renders human iPSC-derived macrophages permissive forM. tuberculosisby rewiring organelle function and metabolism

Bussi,

Lai,

Athanasiade

et al. 2024

Preprint

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Ferroptosis susceptibility of melanoma cells: dependence on cell-type, acquired drug resistance, and medium composition

Preis,

Rolvering,

Kirchmeyer

et al. 2024

Preprint

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Resistance of melanoma cells to targeted therapy (BRAF and MEK inhibitors) is a major clinical problem and alternative treatments are sought. We describe the establishment of modular physiologic medium (MPM) and Mel-MPM (which contains additional supplements and sustains the 3D growth of melanoma cells, fibroblasts (NHDFs) and HMEC-1 endothelial cells) as novel resources for melanoma and combine them with a multi-cell-type matrix-embedded 3D culture model to investigate melanoma cell vulnerabilities in a more physiological setting.We made use of the modular nature of MPM to interrogate NEAA dependencies in melanoma cells and we found them to be particularly sensitive to the depletion of C/C. We additionally describe that melanoma cells are less sensitive to ferroptosis inducing compounds when cultured in MPM compared to RPMI and we could attribute this to different components of MPM and Mel-MPM (selenite, B27). Cell death induced by the glutathione peroxidase 4 inhibitor, ML162, had characteristics of ferroptosis or apoptosis depending on cell type, its drug resistance status and the culture medium. Cystine/cysteine starvation and ML162 treatment combinations increased melanoma cell death in 2D, 3D, and also in the complex matrix embedded multi-cell-type-3D system in OrganoplatesTM. This underlines the potential of combining metabolism-oriented drug treatments with amino acid starvation conditions, which is of interest in view of future therapeutic approaches to combat melanoma and other cancer types.

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Physiologic medium renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

Bussi,

Lai,

Athanasiadi

et al. 2024

mBio

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In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analyzed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarization. Functionally, we discovered that HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-differentiated macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function. IMPORTANCE This work compellingly demonstrates that the choice of culture medium significantly influences M. tuberculosis replication outcomes, thus emphasizing the importance of employing physiologically relevant media for accurate in vitro host-pathogen interaction studies. We anticipate that our work will set a precedent for future research with clinical relevance, particularly in evaluating antibiotic efficacy and resistance in cellulo .

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Physiologically relevant culture medium Plasmax improves human placental trophoblast stem cell function

Cited by 3 publications

References 24 publications

Physiologic media renders human iPSC-derived macrophages permissive forM. tuberculosisby rewiring organelle function and metabolism

Physiologic media renders human iPSC-derived macrophages permissive forM. tuberculosisby rewiring organelle function and metabolism

Ferroptosis susceptibility of melanoma cells: dependence on cell-type, acquired drug resistance, and medium composition

Physiologic medium renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism

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