The lack of a fully developed human cardiac model in vitro hampers the progress of many biomedical research fields including pharmacology, developmental biology, and disease modeling. Currently, available methods may only differentiate human induced pluripotent stem cells (iPSCs) into immature cardiomyocytes. To achieve cardiomyocyte maturation, appropriate modulation of cellular microenvironment is needed. This study aims to optimize a microfluidic system that enhances maturation of human iPSC-derived cardiomyocytes (iPSC-CMs) through cyclic pulsatile hemodynamic forces. Human iPSC-CMs cultured in the microfluidic system show increased alignment and contractility and appear more rod-like shaped with increased cell size and increased sarcomere length when compared to static cultures. Increased complexity and density of the mitochondrial network in iPSC-CMs cultured in the microfluidic system are in line with expression of mitochondrial marker genes MT-CO1 and OPA1. Moreover, the optimized microfluidic system is capable of stably maintaining controlled oxygen levels and inducing hypoxia, revealed by increased expression of HIF1α and EGLN2 as well as changes in contraction parameters in iPSC-CMs. In summary, this microfluidic system boosts the structural maturation of iPSC-CM culture and could serve as an advanced in vitro cardiac model for biomedical research in the future. STATEMENT OF SIGNIFICANCE: The availability of in vitro human cardiomyocytes generated from induced pluripotent stem cells (iPSCs) opens the possibility to develop human in vitro heart models for disease modeling and drug testing. However, iPSC-derived cardiomyocytes remain structurally and functionally immature, which hinders their application. In this manuscript, we present an optimized and complete microfluidic system that enhances maturation of iPSC-derived cardiomyocytes through physiological cyclic pulsatile hemodynamic forces. Furthermore, we improved our microfluidic system by using a closed microfluidic recirculation and oxygen exchangers to achieve and maintain low oxygen in the culture chambers, which is suitable for mimicking the hypoxic condition and studying the pathophysiological mechanisms of human diseases in vitro. In the future, a variety of technologies including 3D tissue engineering could be integrated into our system, which may greatly extend the use of iPSC-derived cardiac models in drug development and disease modeling.
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http://dx.doi.org/10.1016/j.actbio.2019.11.044 | DOI Listing |
Adv Sci (Weinh)
December 2024
Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.
Osteoarthritis (OA) is a leading cause of disability, often resulting from overuse or injury, but inactivity can also contribute to cartilage degeneration. Conventional in vivo models struggle to isolate and study the specific effects of mechanical stress on cartilage health. To address this limitation, a microphysiological system (MPS) is established to examine how varying levels of shear stress impact cartilage homeostasis.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
The current understanding of the human auditory system has been primarily based on studies using animal and cellular models. Organoids have been used to simulate cochlear structures and replicate cochlear functions. However, the physical and chemical cues required to control the development of cochlear organoids accurately remain poorly understood, limiting research advances on cochlea-on-a-chip systems.
View Article and Find Full Text PDFInt J Cancer
December 2024
Junior Research Group Epithelium Microbiome Interactions (EMIL), German Cancer Research Center, Heidelberg, Germany.
The biology of cancer is characterized by an intricate interplay of cells originating not only from the tumor mass, but also its surrounding environment. Different microbial species have been suggested to be enriched in tumors and the impacts of these on tumor phenotypes is subject to intensive investigation. For these efforts, model systems that accurately reflect human-microbe interactions are rapidly gaining importance.
View Article and Find Full Text PDFJMIR Biomed Eng
December 2024
School of Interactive Computing, Georgia Institute of Technology, Atlanta, GA, United States.
Background: Cell concentration in body fluid is an important factor for clinical diagnosis. The traditional method involves clinicians manually counting cells under microscopes, which is labor-intensive. Automated cell concentration estimation can be achieved using flow cytometers; however, their high cost limits accessibility.
View Article and Find Full Text PDFACS Omega
December 2024
Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
In this study, we realized a real-time and enzyme-free measurement of lactate in sweat in the same way as an enzyme-based amperometric method. A conductive polymer, which is based on polyaniline (PANI), was strongly coated on a glassy carbon electrode as a poly -aminophenylboronic acid (PANI-PBA) membrane by drop-casting, which is a convenient method, owing to adhesive phytic acid (PA) molecules with negative charges included as a dopant. This polymer membrane had a functional structure with PBA in the PANI main chain, which expectedly induced electrical charges upon diol binding to lactate, owing to the formation of deprotonated boronate esters with negative charges.
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