Biomimetic aorta-gonad-mesonephros-on-a-chip to study human developmental hematopoiesis

Sugimura, Ryohichi; Ohta, Ryo; Mori, Chihiro; Li, Alina; Mano, Takafumi; Sano, Emi; Kosugi, Kaori; Nakahata, Tatsutoshi; Niwa, Akira; Saito, Megumu K.; Torisawa, Yu-suke

doi:10.1007/s10544-020-00488-2

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Several recent reports have demonstrated the utility of organ-on-a-chip (Ooc) solutions for the recreation of adult bone marrow environments in physiological (Sugimura et al, 2020; Torisawa et al, 2014) and pathological (Abdullah Obaid Khan et al, 2022; Chou et al, 2020), i.e. leukemia settings.…”

Section: Discussionmentioning

confidence: 99%

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

Ragusa

Suen

Cortes

et al. 2022

Preprint

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Current in vitro models of developmental blood formation lack spatiotemporal coherence and weakly replicate the hematopoietic microenvironment. Developmentally-appropriate models can enhance understanding of infant acute myeloid leukemia (infAML), which putatively originates in utero and has 50% age-unique genetic events, suggesting unique biology. The commonest genetic abnormality unique to infants involves homeobox gene MNX1, whose leukemogenic mechanisms remain unknown. Recently, 3D self-organising embryonic stem cell (SC)-based gastruloids have shown promise in recapitulating embryonic events with time/space precision. Herein, we report a hemogenic gastruloid (haemGx) system that captures multi-wave blood formation, progenitor specification from hemogenic endothelium (HE), and approximates generation of hematopoietic SC precursors. Enforced MNX1 expression in haemGx promotes HE formation, perturbs endothelial-to-hemogenic transition, and critically achieves transformation, generating myeloid colonies which display MNX1 AML signatures. By combining functional assays with single-cell transcriptomics, we establish the haemGx as a new model of normal and leukemic embryonic hematopoiesis amenable to mechanistic exploration.

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Section: Discussionmentioning

confidence: 99%

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

Ragusa

Suen

Cortes

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Microfabrication strategies have been used to dissect the role of mechanical, spatial, and temporal signals controlling the hemogenic niche (Lundin et al, 2020;Rahman et al, 2017;Sugimura et al, 2020;Tewary et al, 2019). The formation of SOX17-mCHERRY + endothelial vessels and release of blood precursor cells into the artificial circulation may be related to channel geometry, wall shear stress, or the accumulation of signaling molecules in recirculated conditioned medium.…”

Section: Discussionmentioning

confidence: 99%

“…Also, wall shear stress and circumferential stretch were shown to promote EHT on monolayers of hemogenic endothelial cells derived from mouse and human PSCs (Adamo et al, 2009;Lundin et al, 2020). Sugimura et al (2020) developed a multilayer microfluidic membrane device to study hemogenic endothelium using coculture systems, but did not study the HOXA + hemogenic niche and AGM hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development

Lao

Bruveris

et al. 2022

Cell Reports

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“…Compared with conventional in vivo animal models and in vitro planar cell models, emerging tumor-on-chip platforms integrating microfluidics, tissue engineering, and 3D cell culture have successfully mimicked the key structural and functional properties of TME in vivo 189 - 191 . Several studies have attempted to generate functional immune cells from human pluripotent stem cells in combination with neo-platforms, such as the generation of T-cell progenitors from hematopoietic organoids 192 and the invention of hematopoietic organs-on-chips 193 . The studies pushed the limit of pluripotent stem cells to produce immune cells useful for CAR-T therapy.…”

Section: Future Directions For Car-t Cell To Optimize Timementioning

confidence: 99%

Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy

Zhou¹,

Dang²,

Xu³

et al. 2022

Theranostics

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Chimeric antigen receptor (CAR)-T cell therapy represents a landmark advance in personalized cancer treatment. CAR-T strategy generally engineers T cells from a specific patient with a new antigen-specificity, which has achieved considerable success in hematological malignancies, but scarce benefits in solid tumors. Recent studies have demonstrated that tumor immune microenvironment (TIME) cast a profound impact on the immunotherapeutic response. The immunosuppressive landscape of TIME is a critical obstacle to the effector activity of CAR-T cells. Nevertheless, every cloud has a silver lining. The immunosuppressive components also shed new inspiration on reshaping a friendly TIME by targeting them with engineered CARs. Herein, we summarize recent advances in disincentives of TIME and discuss approaches and technologies to enhance CAR-T cell efficacy via addressing current hindrances. Simultaneously, we firmly believe that by parsing the immunosuppressive components of TIME, rationally manipulating the complex interactions of immunosuppressive components, and optimizing CAR-T cell therapy for each patient, the CAR-T cell immunotherapy responsiveness for solid malignancies will be substantially enhanced, and novel therapeutic targets will be revealed.

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Biomimetic aorta-gonad-mesonephros-on-a-chip to study human developmental hematopoiesis

Cited by 7 publications

References 22 publications

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

Mimicry of embryonic circulation enhances the hoxa hemogenic niche and human blood development

Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy

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