Development of Human Gut Organoids With Resident Tissue Macrophages as a Model of Intestinal Immune Responses

Tsuruta, Satoru; Kawasaki, Tomoyuki; Machida, Masakazu; Iwatsuki, Ken; Inaba, Akihiko; Shibata, Shinsuke; Shindo, Tomoko; Nakabayashi, Kazuhiko; Hakamada, Kenichi; Umezawa, Akihiro; Akutsu, Hidenori

doi:10.1016/j.jcmgh.2022.06.006

Cited by 12 publications

(5 citation statements)

References 16 publications

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“…Importantly, recent advances in the analysis of human tissues including singe-cell approaches 147 have documented that the cell types and regulatory processes identified in mice also are operative in the human intestine. It indeed is likely that the advanced methodologies available to researchers today, from advanced mouse genetic models that can target any gene in vivo, whether in the stroma or epithelium and complex organoid models that even allow for the inclusion of immune cells to model inflammatory bowel disease, 153 to the powerful epigenomic methodologies that enable analysis of transcriptomes and epigenomes at the single-cell level (for a recent example see Burclaff et al 154 ) will enable researchers worldwide to completely elucidate mammalian intestinal development in the near future. Going forward, it will be of particular interest to exploit the new spatial transcriptomic methodologies, which examine transcript levels of thousands of genes while retaining spatial resolution of complex small and large intestine architecture, 155 not just during development but also in human diseases such as Crohn’s disease, ulcerative colitis, and cancer.…”

Section: Discussionmentioning

confidence: 99%

Mammalian Intestinal Development and Differentiation—The State of the Art

Kolev¹,

Kaestner²

2023

Cellular and Molecular Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 99%

Mammalian Intestinal Development and Differentiation—The State of the Art

Kolev¹,

Kaestner²

2023

Cellular and Molecular Gastroenterology and Hepatology

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“…Zhang et al, 2021). Co-cultures with different cell types, including immune and nerve cells (Schreurs et al, 2021;Tominaga et al, 2022;Tsuruta et al, 2022), the combination of multiple organoids or the integration of organoids with missing cell types or primary tissue explants (assembloids; Kanton & Paşca, 2022;Shek et al, 2021), as well as approaches to replicate the complex dynamic tissue environment encompassing continuously flowing fluid systems or to replicate multi-organ interactions have been established (Park et al, 2019), for example, fluidic bioreactors or OoC/microphysiological systems (MPS). An overview of the main current or potential applications TA B L E 4 An overview of the main current or potential applications of human induced pluripotent stem cells (iPSCS) and iPSCs-derived organoids in nutrition research, along with their most important limitations and the possible ways to overcome these limitations.…”

Section: General Limitationsmentioning

confidence: 99%

“…For example, co‐culture with mesenchymal stem cells, endothelial cells, and specific growth factors on innovative 3D substrate matrix, as well as 3D bioprinting, allow to generate latest generation vascularized organoids (Dellaquila et al., 2021; Ren et al., 2021; S. Zhang et al., 2021). Co‐cultures with different cell types, including immune and nerve cells (Schreurs et al., 2021; Tominaga et al., 2022; Tsuruta et al., 2022), the combination of multiple organoids or the integration of organoids with missing cell types or primary tissue explants (assembloids; Kanton & Paşca, 2022; Shek et al., 2021), as well as approaches to replicate the complex dynamic tissue environment encompassing continuously flowing fluid systems or to replicate multi‐organ interactions have been established (Park et al., 2019), for example, fluidic bioreactors or OoC/microphysiological systems (MPS). An overview of the main current or potential applications of iPSCs and iPSCs‐derived organoids in nutrition research, along with their most important limitations and the possible ways to overcome these limitations, is presented in Table 4.…”

Section: Nams For Nutrition Researchmentioning

confidence: 99%

Human‐based new approach methodologies to accelerate advances in nutrition research

Cassotta,

Cianciosi,

Elexpuru‐Zabaleta

et al. 2024

Food Frontiers

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Much of nutrition research has been conventionally based on the use of simplistic in vitro systems or animal models, which have been extensively employed in an effort to better understand the relationships between diet and complex diseases as well as to evaluate food safety. Although these models have undeniably contributed to increase our mechanistic understanding of basic biological processes, they do not adequately model complex human physiopathological phenomena, creating concerns about the translatability to humans. During the last decade, extraordinary advancement in stem cell culturing, three‐dimensional cell cultures, sequencing technologies, and computer science has occurred, which has originated a wealth of novel human‐based and more physiologically relevant tools. These tools, also known as “new approach methodologies,” which comprise patient‐derived organoids, organs‐on‐chip, multi‐omics approach, along with computational models and analysis, represent innovative and exciting tools to forward nutrition research from a human‐biology‐oriented perspective. After considering some shortcomings of conventional in vitro and vivo approaches, here we describe the main novel available and emerging tools that are appropriate for designing a more human‐relevant nutrition research. Our aim is to encourage discussion on the opportunity to explore innovative paths in nutrition research and to promote a paradigm‐change toward a more human biology‐focused approach to better understand human nutritional pathophysiology, to evaluate novel food products, and to develop more effective targeted preventive or therapeutic strategies while helping in reducing the number and replacing animals employed in nutrition research.

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“…As the imbalance among those components manifests as immunological disorders in the intestinal tract, reconstruction of the immune niche within the organoids is essential to closely mimic the pathogenesis of these diseases [94,97]. In this context, Tsuruta et al [98] recently attempted to partially create an intestinal immune milieu by directly injecting iPSC-derived monocyte-like cells into the cavity of iPSC-derived gut organoids. In another implementation, cerebral organoids containing microglia populations obtained from iPSC-derived hematopoietic progenitor cells have also been produced with this reductionist approach [17,99].…”

Section: Recapitulation Of Immune System Within the Organoid: A Platf...mentioning

confidence: 99%

Induced pluripotent stem cell-derived hematopoietic stem and progenitor cells: potential, challenges, and future perspectives

Han

Kim

2023

Organoid

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Hematopoietic stem and progenitor cells (HSPCs) are responsible for the lifetime dynamics of hematopoiesis, as they are well known for their self-renewing ability and multipotency to differentiate into all types of blood cells, including both myeloid and lymphoid lineages. However, due to their limited amount and accessibility, there is a strong need to search out alternative methods to produce HSPCs. In this review, we suggest induced pluripotent stem cells (iPSCs) as a new viable source for HSPC production because these cells have the potential to self-renew while being relatively easy to modify. Recent studies have revealed that the recapitulation of definitive hematopoiesis is the key to the successful in vitro production of HSPCs with multilineage potential. Therefore, we summarized recent progress in establishing the generation of definitive HSPCs with high maturity and functionality in vitro. Definitive HSPCs can be used in disease modeling and gene therapy for genetic blood disorders via gene modification in iPSCs, applied in cellular immunotherapy in the form of a universal chimeric antigen receptor system, and may recapitulate the intricate immune system within the iPSC-derived organoids that closely mimic the in vivo pathophysiological environment. In summary, this review provides an overview of the generation of HSPCs from iPSCs, in terms of the developmental process of hematopoiesis, in vitro attempts to produce iPSC-derived definitive HSPCs, and the following applications of these cells in numerous areas. This review sheds light on the concept of iPSC-derived definitive HSPCs, setting a milestone for artificial blood production in the near future.

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Development of Human Gut Organoids With Resident Tissue Macrophages as a Model of Intestinal Immune Responses

Cited by 12 publications

References 16 publications

Mammalian Intestinal Development and Differentiation—The State of the Art

Mammalian Intestinal Development and Differentiation—The State of the Art

Human‐based new approach methodologies to accelerate advances in nutrition research

Induced pluripotent stem cell-derived hematopoietic stem and progenitor cells: potential, challenges, and future perspectives

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