Adding the ‘heart’ to hanging drop networks for microphysiological multi-tissue experiments

Yazdi, Saeed Rismani; Shadmani, Amir; Bürgel, Sebastian C.; Misun, Patrick M.; Hierlemann, Andreas; Frey, Olivier

doi:10.1039/c5lc01000d

Cited by 52 publications

(43 citation statements)

References 25 publications

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“…The suspension culture is advantageous in high-throughput production of spheroids, but the disadvantages are limited control over spheroid size and uniformity. The hanging drop method uses microtitre plate or microstructures to inversely hold a cell suspension droplet [41][42][43][44][45][46][47] (figure 2e). The cells aggregate under gravity and subsequently form spheroids inside the droplet.…”

Section: Tumour Spheroidsmentioning

confidence: 99%

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Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

Tsai

Trubelja

Shen

et al. 2017

J. R. Soc. Interface.

179

133

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Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed.

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Section: Tumour Spheroidsmentioning

confidence: 99%

“…The cells aggregate under gravity and subsequently form spheroids inside the droplet. The hanging drop method [44][45][46][47]. Alternative to the hanging droplet method, using the liquid overlay method, cell suspension is cultured on non-adherent substrates to produce spheroids [48][49][50] (figure 2f ).…”

Section: Tumour Spheroidsmentioning

confidence: 99%

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

Tsai

Trubelja

Shen

et al. 2017

J. R. Soc. Interface.

179

133

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“…The reaggregated primary islet model featured representative and homogeneous size and native‐like distribution of endocrine cells within each aggregate, as well as physiologically relevant beta cell function. The microfluidic system design is based on the hanging‐drop technology 39–45. Single islets were loaded into and inherently placed at the bottom of a hanging‐drop.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution

et al. 2020

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Insulin is released from pancreatic islets in a biphasic and pulsatile manner in response to elevated glucose levels. This highly dynamic insulin release can be studied in vitro with islet perifusion assays. Herein, a novel platform to perform glucose‐stimulated insulin secretion (GSIS) assays with single islets is presented for studying the dynamics of insulin release at high temporal resolution. A standardized human islet model is developed and a microfluidic hanging‐drop‐based perifusion system is engineered, which facilitates rapid glucose switching, minimal sample dilution, low analyte dispersion, and short sampling intervals. Human islet microtissues feature robust and long‐term glucose responsiveness and demonstrate reproducible dynamic GSIS with a prominent first phase and a sustained, pulsatile second phase. Perifusion of single islet microtissues produces a higher peak secretion rate, higher secretion during the first and second phases of insulin release, as well as more defined pulsations during the second phase in comparison to perifusion of pooled islets. The developed platform enables to study compound effects on both phases of insulin secretion as shown with two classes of insulin secretagogs. It provides a new tool for studying physiologically relevant dynamic insulin secretion at comparably low sample‐to‐sample variation and high temporal resolution.

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“…The array-based format enables parallel multi-tissue experiments and allowed to reproduce the cyclophosphamide bioactivation study described above. The integration of an on-chip pulsatile micropump, of which stroke rate has been synchronized with the beating of a human iPS-derived cardiac spheroid, recently “added the heart” to the hanging-drop network technology (Rismani et al, 2015). …”

Section: Microphysiological Systems – An Expanding Toolbox For Hazmentioning

confidence: 99%

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing

Marx¹,

Andersson

Bahinski

et al. 2016

ALTEX

193

229

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Summary The recent advent of microphysiological systems – microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro – is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-five experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.

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Adding the ‘heart’ to hanging drop networks for microphysiological multi-tissue experiments

Cited by 52 publications

References 25 publications

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

In Vitro Platform for Studying Human Insulin Release Dynamics of Single Pancreatic Islet Microtissues at High Resolution

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing

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