A new microfluidic model that allows monitoring of complex vascular structures and cell interactions in a 3D biological matrix

Dijk, Christian G.M. van; Brandt, Maarten M.; Poulis, Nikolaos; Anten, Jonas; Moolen, Matthijs van der; Kramer, Liana; Homburg, Erik; Louzao-Martinez, Laura; Pei, Jiayi; Krebber, Merle M.; Balkom, Bas W. M. van; Graaf, Petra de; Duncker, Dirk J.; Verhaar, Marianne C.; Lüttge, Regina; Cheng, Caroline

doi:10.1039/d0lc00059k

Cited by 54 publications

(48 citation statements)

References 96 publications

(111 reference statements)

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“…Importantly, most studies presenting in vitro BM systems used scaffolds 18,48 , gels 25,42,[49][50][51] , or microfluidic devices 20,21,41,43,52 to obtain complex endothelial networks in vitro. We demonstrate here that ECs have the potential to self-organize in a complex architectural network within mesenchymal cells without additional support, reminiscent of the organization found in the vascular BM.…”

Section: Discussionmentioning

confidence: 99%

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Giger

Hofer

Miljkovic‐Licina

et al. 2021

Preprint

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In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such a vascular compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays.

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Section: Discussionmentioning

confidence: 99%

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Giger

Hofer

Miljkovic‐Licina

et al. 2021

Preprint

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“…Typically, ECs are directly populated within hydrogels, which are then embedded within the microfluidic device and ultimately self-assemble into angiogenic networks [ 81 , 173 ]. As for this angiogenesis-on-a-chip approach, ECs sprouting, secretion of matrix proteins, the release of GFs, cellular interactions, and perivascular cell recruitments can be recapitulated and monitored to some extent within hydrogel matrixes [ 182 , 183 ]. For example, Kim and coworkers provided a dynamic methodology that could monitor the complex angiogenesis and vasculogenesis progress directed by ECs in response to microenvironment factors [ 181 ].…”

Section: Potential Applicationsmentioning

confidence: 99%

Advances in hydrogel-based vascularized tissues for tissue repair and drug screening

Wang

Kankala

et al. 2022

Bioactive Materials

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The construction of biomimetic vasculatures within the artificial tissue models or organs is highly required for conveying nutrients, oxygen, and waste products, for improving the survival of engineered tissues in vitro . In recent times, the remarkable progress in utilizing hydrogels and understanding vascular biology have enabled the creation of three-dimensional (3D) tissues and organs composed of highly complex vascular systems. In this review, we give an emphasis on the utilization of hydrogels and their advantages in the vascularization of tissues. Initially, the significance of vascular elements and the regeneration mechanisms of vascularization, including angiogenesis and vasculogenesis, are briefly introduced. Further, we highlight the importance and advantages of hydrogels as artificial microenvironments in fabricating vascularized tissues or organs, in terms of tunable physical properties, high similarity in physiological environments, and alternative shaping mechanisms, among others. Furthermore, we discuss the utilization of such hydrogels-based vascularized tissues in various applications, including tissue regeneration, drug screening, and organ-on-chips. Finally, we put forward the key challenges, including multifunctionalities of hydrogels, selection of suitable cell phenotype, sophisticated engineering techniques, and clinical translation behind the development of the tissues with complex vasculatures towards their future development.

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“…Methods to engineer heart-on-a-chip or vessel-on-a-chip are numerous and various, but are predominantly based on microfluidic technology and commonly involve culture of cardiovascular cells on polydimethylsiloxane (PDMS) devices, which have the advantages of being flexible and optical transparent [115]. The native tissue environment is recreated with architectural structure, contractile properties, simulation of vessel flow, through controllable shear stresses imitating hemodynamic forces, uniaxial cyclic strains and application of electric fields generating a synchronous beating activity, perfusable microchannels for efficient delivery of oxygen and nutrients [116][117][118][119].…”

Section: D Organ-on-a-chipmentioning

confidence: 99%

Human Cell Modeling for Cardiovascular Diseases

Lippi

Stadiotti

Pompilio

et al. 2020

IJMS

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The availability of appropriate and reliable in vitro cell models recapitulating human cardiovascular diseases has been the aim of numerous researchers, in order to retrace pathologic phenotypes, elucidate molecular mechanisms, and discover therapies using simple and reproducible techniques. In the past years, several human cell types have been utilized for these goals, including heterologous systems, cardiovascular and non-cardiovascular primary cells, and embryonic stem cells. The introduction of induced pluripotent stem cells and their differentiation potential brought new prospects for large-scale cardiovascular experiments, bypassing ethical concerns of embryonic stem cells and providing an advanced tool for disease modeling, diagnosis, and therapy. Each model has its advantages and disadvantages in terms of accessibility, maintenance, throughput, physiological relevance, recapitulation of the disease. A higher level of complexity in diseases modeling has been achieved with multicellular co-cultures. Furthermore, the important progresses reached by bioengineering during the last years, together with the opportunities given by pluripotent stem cells, have allowed the generation of increasingly advanced in vitro three-dimensional tissue-like constructs mimicking in vivo physiology. This review provides an overview of the main cell models used in cardiovascular research, highlighting the pros and cons of each, and describing examples of practical applications in disease modeling.

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A new microfluidic model that allows monitoring of complex vascular structures and cell interactions in a 3D biological matrix

Abstract: We present a microfluidic vascular device. Vascular cells in a 3D-ECM environment support hemodynamic flow and enable monocyte interaction.

Cited by 54 publications

References 96 publications

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Advances in hydrogel-based vascularized tissues for tissue repair and drug screening

Human Cell Modeling for Cardiovascular Diseases

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