bims-orenst 2021-10-24 papers

Issue of 2021–10–24
five papers selected by
Joram Mooiweer, University of Groningen

Micromachines (Basel). 2021 Oct 15. pii: 1253. [Epub ahead of print]12(10):

Microfluidic Bioreactor Made of Cyclo-Olefin Polymer for Observing On-Chip Platelet Production.

Hiroki Kumon, Shinya Sakuma, Sou Nakamura, Hisataka Maruyama, Koji Eto, Fumihito Arai.

We previously proposed a microfluidic bioreactor with glass-Si-glass layers to evaluate the effect of the fluid force on platelet (PLT) production and fabricated a three-dimensional (3D) microchannel by combining grayscale photolithography and deep reactive ion etching. However, a challenge remains in observing the detailed process of PLT production owing to the low visibility of the microfluidic bioreactor. In this paper, we present a transparent microfluidic bioreactor made of cyclo-olefin polymer (COP) with which to observe the process of platelet-like particle (PLP) production under a bright-field, which allows us to obtain image data at a high sampling rate. We succeeded in fabricating the COP microfluidic bioreactor with a 3D microchannel. We investigated the bonding strength of COP-COP layers and confirmed the effectiveness of the microfluidic bioreactor. Results of on-chip PLP production using immortalized megakaryocyte cell lines (imMKCLs) derived from human-induced pluripotent stem cells show that the average total number of produced PLPs per imMKCL was 17.6 PLPs/imMKCL, which is comparable to that of our previous glass-Si-glass microfluidic bioreactor (17.4 PLPs/imMKCL). We succeeded in observing PLP production under a bright-field using the presented microfluidic bioreactor and confirmed that PLP fragmented in a narrow area of proplatelet-like protrusions.

Keywords: bioreactor; cyclo-olefin polymer; fabrication; microfluidic chip; platelet; three-dimensional microchannel

DOI: https://doi.org/10.3390/mi12101253

Front Bioeng Biotechnol. 2021 ;9 697657

Three-Dimensional In Vitro Lymphangiogenesis Model in Tumor Microenvironment.

Youngkyu Cho, Kyuhwan Na, Yesl Jun, Jihee Won, Ji Hun Yang, Seok Chung.

Lymphangiogenesis is a stage of new lymphatic vessel formation in development and pathology, such as inflammation and tumor metastasis. Physiologically relevant models of lymphatic vessels have been in demand because studies on lymphatic vessels are required for understanding the mechanism of tumor metastasis. In this study, a new three-dimensional lymphangiogenesis model in a tumor microenvironment is proposed, using a newly designed macrofluidic platform. It is verified that controllable biochemical and biomechanical cues, which contribute to lymphangiogenesis, can be applied in this platform. In particular, this model demonstrates that a reconstituted lymphatic vessel has an in vivo-like lymphatic vessel in both physical and biochemical aspects. Since biomechanical stress with a biochemical factor influences robust directional lymphatic sprouting, whether our model closely approximates in vivo, the initial lymphatics in terms of the morphological and genetic signatures is investigated. Furthermore, attempting an incorporation with a tumor spheroid, this study successfully develops a complex tumor microenvironment model for use in lymphangiogenesis and reveals the microenvironment factors that contribute to tumor metastasis. As a first attempt at a coculture model, this reconstituted model is a novel system with a fully three-dimensional structure and can be a powerful tool for pathological drug screening or disease model.

Keywords: interstitial flow; lymphangiogenesis; lymphatic vessel; organ-on-a-chip; tumor microenvironment

DOI: https://doi.org/10.3389/fbioe.2021.697657

Biomicrofluidics. 2021 Sep;15(5): 051301

Facilitating implementation of organs-on-chips by open platform technology.

Anke R Vollertsen, Aisen Vivas, Berend van Meer, Albert van den Berg, Mathieu Odijk, Andries D van der Meer.

Organ-on-chip (OoC) and multi-organs-on-chip (MOoC) systems have the potential to play an important role in drug discovery, disease modeling, and personalized medicine. However, most devices developed in academic labs remain at a proof-of-concept level and do not yet offer the ease-of-use, manufacturability, and throughput that are needed for widespread application. Commercially available OoC are easier to use but often lack the level of complexity of the latest devices in academia. Furthermore, researchers who want to combine different chips into MOoC systems are limited to one supplier, since commercial systems are not compatible with each other. Given these limitations, the implementation of standards in the design and operation of OoCs would strongly facilitate their acceptance by users. Importantly, the implementation of such standards must be carried out by many participants from both industry and academia to ensure a widespread acceptance and adoption. This means that standards must also leave room for proprietary technology development next to promoting interchangeability. An open platform with standardized interfacing and user-friendly operation can fulfill these requirements. In this Perspective article, the concept of an open platform for OoCs is defined from a technical perspective. Moreover, we discuss the importance of involving different stakeholders in the development, manufacturing, and application of such an open platform.

DOI: https://doi.org/10.1063/5.0063428

Adv Sci (Weinh). 2021 Oct 18. e2102640

Cancer Patient Tissueoid with Self-Homing Nano-Targeting of Metabolic Inhibitor.

Hyo-Jin Yoon, Young Shin Chung, Yong Jae Lee, Seung Eun Yu, Sewoom Baek, Hye-Seon Kim, Sang Wun Kim, Jung-Yun Lee, Sunghoon Kim, Hak-Joon Sung.

The current paradigm of cancer medicine focuses on patient- and/or cancer-specific treatments, which has led to continuous progress in the development of patient representatives (e.g., organoids) and cancer-targeting carriers for drug screening. As breakthrough concepts, i) living cancer tissues convey intact profiles of patient-specific microenvironmental signatures. ii) The growth mechanisms of cancer mass with intense cell-cell interactions can be harnessed to develop self-homing nano-targeting by using cancer cell-derived nanovesicles (CaNVs). Hence, a tissueoid model of ovarian cancer (OC) is developed by culturing OC patient tissues in a 3D gel chip, whose microchannel networks enable perfusion to maintain tissue viability. A novel model of systemic cancer responses is approached by xenografting OC tissueoids into ischaemic hindlimbs in nude mice. CaNVs are produced to carry general chemotherapeutics or new drugs under pre/clinical studies that target the BRCA mutation or energy metabolism, thereby increasing the test scope. This pioneer study cross-validates drug responses from the OC clinic, tissueoid, and animal model by demonstrating the alignment of results in drug type-specific efficiency, BRCA mutation-dependent drug efficiency, and metabolism inhibition-based anti-cancer effects. Hence, this study provides a directional foundation to accelerate the discovery of patient-specific drugs with CaNV application towards future precision medicine.

Keywords: cancer cell-derived nanovesicles; ovarian cancer; patient-specific treatments; self-homing nano-targeting; tissueoid

DOI: https://doi.org/10.1002/advs.202102640

ACS Biomater Sci Eng. 2021 Oct 20.

milliPillar: A Platform for the Generation and Real-Time Assessment of Human Engineered Cardiac Tissues.

Manuel Alejandro Tamargo, Trevor Ray Nash, Sharon Fleischer, Youngbin Kim, Olaia Fernandez Vila, Keith Yaeger, Max Summers, Yimu Zhao, Roberta Lock, Miguel Chavez, Troy Costa, Gordana Vunjak-Novakovic.

Engineered cardiac tissues derived from human induced pluripotent stem cells (iPSCs) are increasingly used for drug discovery, pharmacology and in models of development and disease. While there are numerous platforms to engineer cardiac tissues, they often require expensive and nonconventional equipment and utilize complex video-processing algorithms. As a result, only specialized academic laboratories have been able to harness this technology. In addition, methodologies and tissue features have been challenging to reproduce between different groups and models. Here, we describe a facile technology (milliPillar) that covers the entire pipeline required for studies of engineered cardiac tissues. We include methodologies for (i) platform fabrication, (ii) cardiac tissue generation, (iii) electrical stimulation, (iv) automated real-time data acquisition, and (v) advanced video analyses. We validate these methodologies and demonstrate the versatility of the platform by showcasing the fabrication of tissues in different hydrogel materials and using cardiomyocytes derived from different iPSC lines in combination with different types of stromal cells. We also validate the long-term culture of tissues within the platform and provide protocols for automated analysis of force generation and calcium flux using both brightfield and fluorescence imaging. Lastly, we demonstrate the compatibility of the milliPillar platform with electromechanical stimulation to enhance cardiac tissue function. We expect that this resource will provide a valuable and user-friendly tool for the generation and real-time assessment of engineered human cardiac tissues for basic and translational studies.

Keywords: cardiac tissue engineering; cardiomyocytes; electromechanical stimulation; induced pluripotent stem cells; organs-on-a-chip; real-time imaging

DOI: https://doi.org/10.1021/acsbiomaterials.1c01006