bims-orenst Biomed News
on Organs-on-chips and engineered stem cell models
Issue of 2020‒12‒06
five papers selected by
Joram Mooiweer
University of Groningen

  1. Micromachines (Basel). 2020 Nov 28. pii: E1054. [Epub ahead of print]11(12):
      Lung-on-a-chip devices could provide new strategies for a biomimetic lung cell microenvironment and construction of lung disease models in vitro, and are expected to greatly promote the development of drug evaluation, toxicological detection, and disease model building. In this study, we developed a novel poly (lactic-co-glycolic acid) (PLGA) nanofiber/polydimethylsiloxane (PDMS) microporous composite membrane-sandwiched lung-on-a-chip to perform anti-tumor drug testing. The composite membrane was characterized, and the results showed that it was permeable to molecules and thus could be used to study small-molecule drug diffusion. In addition, the microchip could apply perfusion fluids to simulate blood flow under extremely low fluid shear stress, and could also simulate the spherical-like shape of the alveoli by deformation of the composite membrane. Using this chip, we evaluated the anti-tumor drug efficacy of gefitinib in two kinds of non-small cell lung cancer cells, the lung adenocarcinoma NCI-H1650 cell line and the large cell lung cancer NCI-H460 cell line. We further probed the resistance of NCI-H460 cells to gefitinib under normoxic and hypoxic conditions. The established composite membrane-sandwiched lung chip can simulate more biochemical and biophysical factors in the lung physiological and pathological microenvironment, and it has important applications in the personalized treatment of lung tumors. It is expected to play a potential role in clinical diagnosis and drug screening.
    Keywords:  composite membrane; drug evaluation; lung-on-a-chip; microfluidic chip; organ-on-a-chip
  2. Micromachines (Basel). 2020 Nov 30. pii: E1066. [Epub ahead of print]11(12):
      Oral mucosa and salivary gland are composed of complex and dynamic networks of extracellular matrix, multiple cell types, vasculature, and various biochemical agents. Two-dimensional (2D) cell culture is commonly used in testing new drugs and experimental therapies. However, 2D cell culture cannot fully replicate the architecture, physiological, and pathological microenvironment of living human oral mucosa and salivary glands. Recent microengineering techniques offer state of the science cell culture models that can recapitulate human organ structures and functions. This narrative review describes emerging in vitro models of oral and salivary gland tissue such as 3D cell culture models, spheroid and organoid models, tissue-on-a-chip, and functional decellularized scaffolds. Clinical applications of these models are also discussed in this review.
    Keywords:  3D cell culture; microengineering; oral mucosa; salivary gland
  3. Biosens Bioelectron. 2020 Nov 13. pii: S0956-5663(20)30804-6. [Epub ahead of print] 112818
      Spatial manipulation of suspended cells based on their properties is an essential part of numerous microfluidic assays. To further read and analyze the manipulation result, a microscopy system is typically required, which, however, increases the cost and reduces the portability of the entire system. As an alternative, a network of integrated Coulter sensors, distributed over a microfluidic chip, provide rapid and reliable detection of spatially-manipulated cells. Code-multiplexing of distributed Coulter sensors enables simplification of such integration by offloading the hardware complexity into advanced signal processing techniques that are needed to interpret the coded sensor outputs. In this work, we combine code-multiplexed Coulter sensor networks with an error-correction technique, a strategy typically used in telecommunication systems for controlling errors in data over unreliable communication channels. Specifically, we include redundancy in the physical sensor design to alleviate the ambiguity in the signal-decoding process, so that interfering sensor signals due to coincidently-detected cells can be resolved reliably. The presented sensor technology not only tracks the spatiotemporal state of cells under test but also measures their sizes and flow speeds. To demonstrate the sensor concept experimentally, we fabricated a microfluidic device with 10 distributed Coulter sensors designed to produce distinct signal waveforms and performed experiments with suspended human cancer cells to characterize the performance of the sensor platform.
    Keywords:  Cell tracking; Coulter sensing; Cytometry; Error-correction; Microfluidics; Sensor network
  4. Int J Mol Sci. 2020 Nov 28. pii: E9075. [Epub ahead of print]21(23):
      Tumor-specific metabolic adaptations offer an interesting therapeutic opportunity to selectively destroy cancer cells. However, solid tumors also present gradients of nutrients and waste products across the tumor mass, forcing tumor cells to adapt their metabolism depending on nutrient availability in the surrounding microenvironment. Thus, solid tumors display a heterogenous metabolic phenotype across the tumor mass, which complicates the design of effective therapies that target all the tumor populations present. In this work, we used a microfluidic device to study tumor metabolic vulnerability to several metabolic inhibitors. The microdevice included a central chamber to culture tumor cells in a three-dimensional (3D) matrix, and a lumen in one of the chamber flanks. This design created an asymmetric nutrient distribution across the central chamber, generating gradients of cell viability. The results revealed that tumor cells located in a nutrient-enriched environment showed low to no sensitivity to metabolic inhibitors targeting glycolysis, fatty acid oxidation, or oxidative phosphorylation. Conversely, when cell density inside of the model was increased, compromising nutrient supply, the addition of these metabolic inhibitors disrupted cellular redox balance and led to tumor cell death.
    Keywords:  microfluidics; redox ratio; tumor metabolism; tumor-on-a-chip
  5. Biotechnol Prog. 2020 Dec 04. e3105
      Drug development is often hindered by the failure of preclinical models to accurately assess and predict the efficacy and safety of drug candidates. Body-on-a-chip (BOC) microfluidic devices, a subset of microphysiological systems (MPS), are being created to better predict human responses to drugs. Each BOC is designed with separate organ chambers interconnected with microfluidic channels mimicking blood recirculation. Here, we describe the design of the first pumpless, unidirectional, multiorgan system and apply this design concept for testing anti-cancer drug treatments. HCT-116 colon cancer spheroids, HepG2/C3A hepatocytes, and HL-60 promyeloblasts were embedded in collagen hydrogels and cultured within compartments representing "colon tumor", "liver", and "bone marrow" tissue, respectively. Operating on a pumpless platform, the microfluidic channel design provides unidirectional perfusion at physiologically realistic ratios to multiple channels simultaneously. The metabolism-dependent toxic effect of Tegafur, an oral prodrug of 5-fluorouracil, combined with uracil was examined in each cell type. Tegafur-uracil treatment induced substantial cell death in HCT-116 cells and this cytotoxic response was reduced for multicellular spheroids compared to single cells, likely due to diffusion-limited drug penetration. Additionally, off-target toxicity was detected by HL-60 cells, which demonstrate that such systems can provide useful information on dose-limiting side effects. Collectively, this microscale cell culture analog is a valuable physiologically-based pharmacokinetic drug screening platform that may be used to support cancer drug development.