January 2025
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6 Reads
Nature Biomedical Engineering
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January 2025
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6 Reads
Nature Biomedical Engineering
December 2024
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37 Reads
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2 Citations
Nature Biomedical Engineering
Organoids for modelling the physiology and pathology of gastrointestinal tissues are constrained by a poorly accessible lumen. Here we report the development and applicability of bilaterally accessible organoid-derived patterned epithelial monolayers that allow the independent manipulation of their apical and basal sides. We constructed gastric, small-intestinal, caecal and colonic epithelial models that faithfully reproduced their respective tissue geometries and that exhibited stem cell regionalization and transcriptional resemblance to in vivo epithelia. The models’ enhanced observability allowed single-cell tracking and studies of the motility of cells in immersion culture and at the air–liquid interface. Models mimicking infection of the caecal epithelium by the parasite Trichuris muris allowed us to live image syncytial tunnel formation. The enhanced observability of bilaterally accessible organoid-derived gastrointestinal tissue will facilitate the study of the dynamics of epithelial cells and their interactions with pathogens.
October 2024
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4 Reads
Trends in Biotechnology
September 2024
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3 Reads
T-cell development depends critically on the thymic stroma, in particular the diverse array of functionally distinct thymic epithelial cell (TEC) types. However, a robust in vitro thymus model mimicking the native thymus and compatible with medium/high-throughput analyses is currently lacking. Here, we demonstrate a novel high-density microwell array-based miniaturized thymus organoid (mTO) model, that supports T-cell commitment and development, possesses key organizational characteristics of the native thymus and is compatible with live-imaging and medium/high-throughput applications. We establish the minimum cellular input required for functional mTO and show that mTO TEC phenotype and complexity closely mirrors the native thymus. Finally, we use mTO to probe the role of fetal thymic mesenchyme, revealing a requirement beyond maintenance of Foxn1 in differentiation/maintenance of mature TEC subpopulations. Collectively, mTO present a new in vitro model of the native thymus adaptable to medium/high-throughput applications and validated for exploration of thymus- and thymus organoid- biology.
August 2024
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63 Reads
npj Precision Oncology
Immunotherapy has emerged as a new standard of care for certain cancer patients with specific cellular and molecular makeups. However, there is still an unmet need for ex vivo models able to readily assess the effectiveness of immunotherapeutic treatments in a high-throughput and patient-specific manner. To address this issue, we have developed a microarrayed system of patient-derived tumoroids with recreated immune microenvironments that are optimized for the high-content evaluation of tumor-infiltrating lymphocyte functionality. Here we show that this system offers unprecedented opportunities to evaluate tumor immunogenicity, characterize the response to immunomodulators, and explore novel approaches for personalized immuno-oncology.
August 2024
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9 Reads
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2 Citations
Cell
July 2024
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29 Reads
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1 Citation
Development
Although the advent of organoids opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here we established organoids from the thymus, the lymphoid organ responsible for T cell development. We identified conditions enabling thymic epithelial progenitor cell proliferation and development into organoids with diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. Contrary to these two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T cell development upon reaggregation with T cell progenitors. The reaggregates showed in vivo-like epithelial diversity and ability to attract T cell progenitors. Thymic epithelial organoids are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries.
July 2024
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170 Reads
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12 Citations
Nature Biotechnology
Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization, biological durability and experimental flexibility. Thus, many multifactorial cancer processes, especially those involving the tumor microenvironment, are difficult to study ex vivo. To overcome these limitations, we herein implemented tissue-engineering and microfabrication technologies to develop topobiologically complex, patient-specific cancer avatars. Focusing on colorectal cancer, we generated miniature tissues consisting of long-lived gut-shaped human colon epithelia (‘mini-colons’) that stably integrate cancer cells and their native tumor microenvironment in a format optimized for real-time, high-resolution evaluation of cellular dynamics. We demonstrate the potential of this system through several applications: a comprehensive evaluation of drug effectivity, toxicity and resistance in anticancer therapies; the discovery of a mechanism triggered by cancer-associated fibroblasts that drives cancer invasion; and the identification of immunomodulatory interactions among different components of the tumor microenvironment. Similar approaches should be feasible for diverse tumor types.
June 2024
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7 Reads
Nature Reviews Genetics
June 2024
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25 Reads
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18 Citations
Cell Stem Cell
... A systematic study is critically needed to confirm this, and this may subsequently allow for the development of appropriate culture conditions and microenvironments which better maintain primary TM cell identity. Since a mechanistic approach was not taken in this study to ascertain why, how and when the divergence in cell identity comparing primary culture to tissues occurs, we point the audience to relatively recent manuscripts/editorials that attempt to draw highlight to this [75][76][77] . With increasing efforts in the use of organoids, microphysiological systems, Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH ("Springer Nature"). ...
August 2024
Cell
... Moreover, in the microsatellite-unstable (MSI) CRC mini-colon where both CAFs and TILs were included, CAFs suppressed T-cell anti-tumor reactivity by promoting the expression of PD-L1. Remarkably, the addition of atezolizumab restored TIL activity also in the presence of CAFs in MSI but not in the microsatellite-stable (MSS) CRC mini-colons [75], clearly demonstrating the superior value of the "mini-colon" device in precision colorectal cancer immunotherapy in a co-clinical setting. ...
July 2024
Nature Biotechnology
... There is a growing demand for useful and reproducible in vitro colonic models to predict human drug absorption accurately. Such models are essential, particularly those that yield results comparable to in vivo data (Apostolou et al., 2021;Marr et al., 2023;Mitrofanova et al., 2024;Rozehnal et al., 2012;Sato et al., 2011). ...
June 2024
Cell Stem Cell
... 18 These organ-on-a-chip systems have been shown to accurately emulate the physiologically relevant microenvironment of the GIT by incorporating factors such as shear stress, exerted by cyclic strain or fluid flow, and nutrient and oxygen gradients, facilitated by the cellular assembly in a villus structure. [18][19][20][21][22][23] Another notable advantage of organ-on-a-chip platforms is the possibility to integrate complementary sensing strategies, enabling non-invasive, in situ, and real-time monitoring of cellular functions. 24 For monitoring an impaired barrier, an important parameter is barrier integrity, which can be analyzed based on the transepithelial electrical resistance (TEER) using, e.g., traditional chopstick electrodes or impedance sensors. ...
April 2024
Nature
... Additionally, this organoid demonstrated typical cholangiocyte receptors: pancreatopoietin and somatostatin. Elci et al. (2024) developed a stable biliary organoid utilizing biliary epithelial cells that displayed essential characteristics of cholangiocytes including transport activity, primary cilium formation, and protective glycocalyx formation over an extended period. Sampaziotis et al. (2019) constructed distinct biliary organoids using human induced pluripotent stem cells (hiPSCs) and primary biliary epithelial cells, which exhibited expression of biliary markers and stable maintenance of biliary cell function. ...
January 2024
... To ensure utility of ArchMap across datasets from different tissues, Archmap is built to ingest high quality reference atlases integrated using different methods. A wide variety of atlases are available on ArchMap, including atlases accepted by the Human Cell Atlas as o cial tissue references 1,11,[13][14][15][16][17][18][19][20][21] . ...
November 2023
... Cell source and isolation B16-F10 melanoma cells and pre-activated Pmel-1 TCR transgenic T-cells were received as a kind gift from the Laboratory of Biomaterials for Immunoengineering (EPFL). Colorectal cancer cells, cancer-associated fibroblasts, tumor-infiltrating lymphocytes, and peripheral monocytes were isolated from matched CRC biopsies and peripheral blood obtained from the Centre Hospitalier Universitaire Vaudois (CHUV) as indicated here (Broguiere et al. 16 Table 1, Supplementary Fig. 1a). THP-1 monocytes were purchased from the ATCC (ATCC, Catalog No. TIB-202). ...
November 2023
... Most studies on steering human intestinal epithelial cells toward a specific lineage or physiological composition use adult stem cell-derived tissues, either as organoids or in static or microfluidic scaffold-based systems 1,[8][9][10] . These studies have yielded widely used compositions of expansion media and several types of differentiation media, depending on the desired lineage. ...
October 2023
... Studies in mouse and human PSCs have elucidated their susceptibility to aneuploidy, as current methodssuch as culture medium, medium acidification, culture density, and extracellular matrixinduce increased stress on the cells (Bai et al., 2015;Ben-David and Benvenisty, 2012;Keller et al., 2019). This has driven rigorous investigations to understand the underlying mechanisms and led to the formation of guidelines for stem cell research and clinical translation by the International Society for Stem Cell Reseach (ISCCR) (Ludwig et al., 2023). However, to the best of our knowledge, no reports were published on the genomic stability of bovine PSCs in longer-term culture. ...
September 2023
Stem Cell Reports
... If this receptivity fails, it results in infertility, including repeated pregnancy loss, which is one of the primary reasons for infertility. The receptivity relies on the cross-talk between endometrium and embryo, and various species models were established to mimic the process [22][23][24][25][26][27][28]. Due to the complexity of the process and ethical limitations of using human embryos, establishing an in vitro model is rare despite their necessity [29]. ...
July 2023
The EMBO Journal