Organ-on-a-chip model of vascularized human bone marrow niches

Glaser, Drew Elizabeth; Curtis, Matthew B.; Sariano, Peter A.; Rollins, Zachary A.; Shergill, Bhupinder; Anand, Aravind; Deely, Alyssa M.; Shirure, Venktesh S.; Anderson, Leif S.; Lowen, Jeremy; Ng, Natalie R.; Weilbaecher, Katherine N.; Link, Daniel C.; George, Steven C.

doi:10.1016/j.biomaterials.2021.121245

Cited by 62 publications

(57 citation statements)

References 62 publications

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“…These microfluidic chambers for co-culture of cancer cells with endothelial cells can also be utilized for tumor spheroids ( Ko et al, 2019 ) and therefore represent an intricate experimental platform for analyzing the migratory capacity through extracellular matrix scaffolds and endothelial barriers. There are also organ-on-a-chip models that fully grasp the 3D microenvironment of cancer cells ( Glaser et al, 2022 ). For example, the immune microenvironment of cancer cells has been analyzed employing these organ-on-a-chip technologies ( Yoon et al, 2020 ).…”

Section: Molecular Mechanosensory Behaviormentioning

confidence: 99%

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

Mierke

2022

Front. Cell Dev. Biol.

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Viscoelasticity and its alteration in time and space has turned out to act as a key element in fundamental biological processes in living systems, such as morphogenesis and motility. Based on experimental and theoretical findings it can be proposed that viscoelasticity of cells, spheroids and tissues seems to be a collective characteristic that demands macromolecular, intracellular component and intercellular interactions. A major challenge is to couple the alterations in the macroscopic structural or material characteristics of cells, spheroids and tissues, such as cell and tissue phase transitions, to the microscopic interferences of their elements. Therefore, the biophysical technologies need to be improved, advanced and connected to classical biological assays. In this review, the viscoelastic nature of cytoskeletal, extracellular and cellular networks is presented and discussed. Viscoelasticity is conceptualized as a major contributor to cell migration and invasion and it is discussed whether it can serve as a biomarker for the cells’ migratory capacity in several biological contexts. It can be hypothesized that the statistical mechanics of intra- and extracellular networks may be applied in the future as a powerful tool to explore quantitatively the biomechanical foundation of viscoelasticity over a broad range of time and length scales. Finally, the importance of the cellular viscoelasticity is illustrated in identifying and characterizing multiple disorders, such as cancer, tissue injuries, acute or chronic inflammations or fibrotic diseases.

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Section: Molecular Mechanosensory Behaviormentioning

confidence: 99%

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

Mierke

2022

Front. Cell Dev. Biol.

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“…This structure could then be retrieved and cultured in vitro within a microfluidic device up to seven days, with appropriate responses to radiation and granulocyte colony-stimulating factor. Recently, Glaser, et al [190] developed a multichamber 3-D organ-on-chip model that demonstrated coculture of an osteoblast cell line with primary human stromal cells, and human hematopoietic stem progenitor cells. This chip recapitulated bone niches that incorporated vascular networks, maintained hematopoietic progenitor cell function, responses to chemotherapy and granulocyte colony-stimulating factor, neutrophil egress, and BC cell line invasion into the bone niches.…”

Section: Bioengineered Microfluidic Modelsmentioning

confidence: 99%

Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment

Sethakorn

Héninger

Sánchez-de-Diego

et al. 2022

Cancers

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Bone metastases represent a lethal condition that frequently occurs in solid tumors such as prostate, breast, lung, and renal cell carcinomas, and increase the risk of skeletal-related events (SREs) including pain, pathologic fractures, and spinal cord compression. This unique metastatic niche consists of a multicellular complex that cancer cells co-opt to engender bone remodeling, immune suppression, and stromal-mediated therapeutic resistance. This review comprehensively discusses clinical challenges of bone metastases, novel preclinical models of the bone and bone marrow microenviroment, and crucial signaling pathways active in bone homeostasis and metastatic niche. These studies establish the context to summarize the current state of investigational agents targeting BM, and approaches to improve BM-targeting therapies. Finally, we discuss opportunities to advance research in bone and bone marrow microenvironments by increasing complexity of humanized preclinical models and fostering interdisciplinary collaborations to translational research in this challenging metastatic niche.

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“…More recently, Glaser et al has also demonstrated that it is possible to study niche-specific functions on BM pathophysiology using a 3D fibrin-based microfluidic co-culture system. For this, the authors have simultaneously used distinct chambers in the same chip that recapitulated either the endosteal and perivascular niches (Glaser et al, 2022). Most interestingly, this system had fully perfusable vascular networks that allowed the maintenance of CD34 + HSCs but also their proliferation and differentiation along myeloid and erythroid lineages with the release and the egress of neutrophils (CD66b + ) through the microvascular network.…”

Section: Bioengineered Organ Modelsmentioning

confidence: 99%

“…Even so, the existing attempts to closely mimic BM niches are best provided by Organ-on-a-chip approaches. These microfluidic-based approaches can be broadly divided by the cell type (single ( Sung and Shuler, 2009 ; Sung et al., 2010 ; Torisawa et al., 2016 ) vs co-culture ( Carrion et al., 2010 ; Khin et al., 2014 ; Zheng et al., 2016 )) and type of tridimensional ECM (Hydrogels ( Thon et al., 2014 ; Torisawa et al., 2014 ; Bruce et al., 2015 ; Aleman et al., 2019 ; McAleer et al., 2019 ; Chou et al., 2020 ; Herland et al., 2020 ; Glaser et al., 2022 ) vs Scaffolds ( Houshmand et al., 2017 ; Marturano-Kruik et al., 2018 ; Sieber et al., 2018 ) vs Cell-generated ECM ( Zhang et al., 2014 ; Zhang et al., 2015 ; Wuchter et al., 2016 )) used for the biomimicry of BM compartments.…”

Section: Organs-on-a-chipmentioning

confidence: 99%

“…Minimal functional units of the spleen-on-a-chip have been reported ( Rigat-Brugarolas et al., 2014 ) ( Elizalde-Torrent et al., 2021 ) ( Picot et al., 2015 ); yet, in addition to rheological studies of infected blood they need now to incorporate ECM matrices and cells. In contrast, elegant OOC of the bone marrow showing sustain expansion of CD34 + cells, differentiation and egress of cells from the chip emulating vascular and bone marrow channels ( Chou et al., 2020 ) ( Glaser et al., 2022 ). It is therefore legitimate to speculate that human bone marrow and spleen OOC models will soon be applied to advance our knowledge of these cryptic erythrocytic infections and to screen for novel drugs as parasites in those niches seem to be shelter from antimalarial drugs ( Lee et al., 2018 ).…”

Section: Organs-on-a-chipmentioning

confidence: 99%

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Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

Aparici-Herraiz

Caires

Castillo-Fernandez

et al. 2022

Front. Cell. Infect. Microbiol.

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Plasmodium vivax is the most widely distributed human malaria parasite representing 36.3% of disease burden in the South-East Asia region and the most predominant species in the region of the Americas. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. However, recent evidence indicates that niches outside the liver, in particular in the spleen and the bone marrow, can represent a major source of cryptic chronic erythrocytic infections. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. Recent advances in the development of humanized mouse models and organs-on-a-chip models, offer novel technological frontiers to study human diseases, vaccine validation and drug discovery. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. vivax cryptic niches, which perpetuate transmission and burden.

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Organ-on-a-chip model of vascularized human bone marrow niches

Cited by 62 publications

References 62 publications

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

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