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  1. AU="Kettunen, Jere"
  2. AU="O'Larey, Timothy D"
  3. AU="Qiu, Tom"
  4. AU="Gindel, Theresa"
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  1. Article ; Online: Highly scalable and standardized organ-on-chip platform with TEER for biological barrier modeling.

    Nguyen, Hoang-Tuan / Rissanen, Siiri-Liisa / Peltokangas, Mimosa / Laakkonen, Tino / Kettunen, Jere / Barthod, Lara / Sivakumar, Ragul / Palojärvi, Anniina / Junttila, Pauliina / Talvitie, Jussi / Bassis, Michele / Nickels, Sarah L / Kalvala, Sara / Ilina, Polina / Tammela, Päivi / Lehtonen, Sarka / Schwamborn, Jens C / Mosser, Sebastien / Singh, Prateek

    Tissue barriers

    2024  , Page(s) 2315702

    Abstract: The development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, ...

    Abstract The development of new therapies is hampered by the lack of predictive, and patient-relevant in vitro models. Organ-on-chip (OOC) technologies can potentially recreate physiological features and hold great promise for tissue and disease modeling. However, the non-standardized design of these chips and perfusion control systems has been a barrier to quantitative high-throughput screening (HTS). Here we present a scalable OOC microfluidic platform for applied kinetic in vitro assays (AKITA) that is applicable for high, medium, and low throughput. Its standard 96-well plate and 384-well plate layouts ensure compatibility with existing laboratory workflows and high-throughput data collection and analysis tools. The AKITA plate is optimized for the modeling of vascularized biological barriers, primarily the blood-brain barrier, skin, and lung, with precise flow control on a custom rocker. The integration of trans-epithelial electrical resistance (TEER) sensors allows rapid and repeated monitoring of barrier integrity over long time periods. Together with automated liquid handling and compound permeability testing analyses, we demonstrate the flexibility of the AKITA platform for establishing human-relevant models for preclinical drug and precision medicine's efficacy, toxicity, and permeability under near-physiological conditions.
    Language English
    Publishing date 2024-02-12
    Publishing country United States
    Document type Journal Article
    ISSN 2168-8370
    ISSN (online) 2168-8370
    DOI 10.1080/21688370.2024.2315702
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Human iPSC and CRISPR targeted gene knock-in strategy for studying the somatic TIE2

    Lazovic, Bojana / Nguyen, Hoang-Tuan / Ansarizadeh, Mohammadhassan / Wigge, Leif / Kohl, Franziska / Li, Songyuan / Carracedo, Miguel / Kettunen, Jere / Krimpenfort, Luc / Elgendy, Ramy / Richter, Kati / De Silva, Laknee / Bilican, Bilada / Singh, Prateek / Saxena, Pratik / Hong, Xuechong / Eklund, Lauri / Hicks, Ryan

    Angiogenesis

    2024  

    Abstract: Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, ... ...

    Abstract Induced pluripotent stem cell (iPSC) derived endothelial cells (iECs) have emerged as a promising tool for studying vascular biology and providing a platform for modelling various vascular diseases, including those with genetic origins. Currently, primary ECs are the main source for disease modelling in this field. However, they are difficult to edit and have a limited lifespan. To study the effects of targeted mutations on an endogenous level, we generated and characterized an iPSC derived model for venous malformations (VMs). CRISPR-Cas9 technology was used to generate a novel human iPSC line with an amino acid substitution L914F in the TIE2 receptor, known to cause VMs. This enabled us to study the differential effects of VM causative mutations in iECs in multiple in vitro models and assess their ability to form vessels in vivo. The analysis of TIE2 expression levels in TIE2
    Language English
    Publishing date 2024-05-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1484717-6
    ISSN 1573-7209 ; 0969-6970
    ISSN (online) 1573-7209
    ISSN 0969-6970
    DOI 10.1007/s10456-024-09925-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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