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  • Technology
  • Products
    • OrganoPlate® 2-lane 96
      • Supporting up to 96 tissue models on a single plate. Its unique PhaseGuide™ technology enables cells to interact and migrate freely between the two channels of each chip.

    • OrganoPlate® 3-lane 40
      • Supporting up to 40 tissue models on a single plate. Its unique PhaseGuide™ technology enables cells to interact and migrate freely between the three channels of each chip.
    • OrganoPlate® 3-lane 64
      • Supporting up to 64 tissue models on a single plate. Specially designed for automated workflows. Its unique PhaseGuide™ technology enables cells to interact and migrate freely between the three channels of each chip.
    • OrganoPlate® Graft
      • The first in vitro tissue culture platform that allows co-culture of spheroids, organoids, and tumors with a perfused microvascular bed and vascularization of 3D tissues.

    • OrganoReady® Colon Caco-2
      • Offering 38 ready-to-use Caco-2 tubules for drug exposure, transport, and permeability studies.
    • OrganoReady® Blood Vessel HUVEC
      • Offering 38 ready-to-use HUVEC tubules for drug exposure, transport, and permeability studies.
    • OrganoReady® Angiogenesis HUVEC
      • Offering 64 ready-to-sprout HUVEC tubules.
    • OrganoFlow®
      • Driving precisely-controlled perfusion flow in the OrganoPlate® platform
    • OrganoTEER®
      • Enabling fast, automated, and impedance-based TEER measurements in OrganoPlate®. Assay 40 tissue culture chips with a few clicks, in less than one minute.
    • Workshops & Trainings
      • Kickstart your experiments with the most sophisticated 3D tissue culture platform. Find out which training fits your 3D tissue modeling needs best.
    • All Products
      • OrganoPlate® is the solution for all in vitro tissue culture applications. Explore the entire OrganoPlate® family and its dedicated instruments here.

    • Getting Started
      • Start with the most sophisticated 3D tissue culture platform today.

    • Request a quote
      • Thinking of using OrganoPlate for your research? Request a quote for the product(s) of your interest.

  • Services
    • Compound profiling & Screening
      • Get robust compound data in human tissue models through our OrganoServices. With proven pheno­typic assays in the OrganoPlate® platform, we support your drug discovery and development needs.
    • Custom Model & Assay Development
      • We create novel human tissue and disease models in the OrganoPlate® platform. Our experts are looking forward to developing assays according to your specifications.
    • Drug Development Partnerships
      • Expand your drug discovery capacity, shoulder to shoulder with our scientific team. Proprietary human disease biology in the OrganoPlate® platform. Together we make the therapeutics of tomorrow.
    • All Services
      • We offer several services to support your drug discovery and development needs. Find the overview here.
  • Applications
    • Perfused Tubules
      • Layered tissues with perfused tubules in the absence of artificial membranes form the heart of our permeability and transport science. Study cell interactions, permeability, absorption, transport, and transcytosis without physical barriers.

    • Cell-Cell Interactions
      • Co-culture layered & structured tissues without artificial membranes with perfect imaging, to study barrier-free cellular interactions, cell-cell signaling, and migration.

    • 3D Cell Migration
      • Evaluate the effect of chemotactic triggers or cells on the migration of cells through an extracellular matrix.

    • Angiogenesis
      • Membrane-free microvascular formation and growth through an extracellular matrix (ECM).

    • Vascularization
      • The missing link in tissue culture: add perfusable human vasculature to your tissue models, and recreate sophisticated microenvironments with OrganoPlate® Graft.

    • All Applications
      • OrganoPlate® enables you to study relevant 3D tissue biology by incorporating perfused tubules, co-culture, and full control over the tissue microenvironment. Find the overview of applications here.

  • Resources & Support
    • Knowledge Center
      • Visit our Knowledge Center to get up to speed with 3D tissue culture and to learn how OrganoPlate® supports your research needs.

        Read our publications, application notes, watch our webinars, or check out the supporting protocols and brochures. All compiled for you, by our scientists.

    • Publications
      • Get inspired by peer-reviewed publications of our scientists, partners, and customers around the globe.

    • Case Studies
      • Get inspired by research done by our scientists, partners, and customers around the globe.

    • Blogs
      • Giving you some food for thought. Read our blogs to learn more about 3D tissue culture, research backgrounds, developments, and its future outlook.
    • Workshops & Trainings
      • Kickstart your experiments with the most sophisticated 3D tissue culture platform. Find out which training fits your 3D tissue modeling needs best.
    • Technical Support
      • Any support questions about purchasing, products, or 3D tissue culture and analysis? Get in touch with our experts.
    • Request a quote
      • Thinking of using OrganoPlate for your research? Request a quote for the product(s) of your interest.

    • FAQ
      • Frequently asked questions answered by our experts. Find here the answer you're looking for.
  • About Mimetas
  • Supporting up to 96 tissue models on a single plate. Its unique PhaseGuide™ technology enables cells to interact and migrate freely between the two channels of each chip.

  • Supporting up to 40 tissue models on a single plate. Its unique PhaseGuide™ technology enables cells to interact and migrate freely between the three channels of each chip.
  • Supporting up to 64 tissue models on a single plate. Specially designed for automated workflows. Its unique PhaseGuide™ technology enables cells to interact and migrate freely between the three channels of each chip.
  • The first in vitro tissue culture platform that allows co-culture of spheroids, organoids, and tumors with a perfused microvascular bed and vascularization of 3D tissues.

  • Offering 38 ready-to-use Caco-2 tubules for drug exposure, transport, and permeability studies.
  • Offering 38 ready-to-use HUVEC tubules for drug exposure, transport, and permeability studies.
  • Offering 64 ready-to-sprout HUVEC tubules.
  • Driving precisely-controlled perfusion flow in the OrganoPlate® platform
  • Enabling fast, automated, and impedance-based TEER measurements in OrganoPlate®. Assay 40 tissue culture chips with a few clicks, in less than one minute.
  • Kickstart your experiments with the most sophisticated 3D tissue culture platform. Find out which training fits your 3D tissue modeling needs best.
  • OrganoPlate® is the solution for all in vitro tissue culture applications. Explore the entire OrganoPlate® family and its dedicated instruments here.

  • Start with the most sophisticated 3D tissue culture platform today.

  • Thinking of using OrganoPlate for your research? Request a quote for the product(s) of your interest.

  • Get robust compound data in human tissue models through our OrganoServices. With proven pheno­typic assays in the OrganoPlate® platform, we support your drug discovery and development needs.
  • We create novel human tissue and disease models in the OrganoPlate® platform. Our experts are looking forward to developing assays according to your specifications.
  • Expand your drug discovery capacity, shoulder to shoulder with our scientific team. Proprietary human disease biology in the OrganoPlate® platform. Together we make the therapeutics of tomorrow.
  • We offer several services to support your drug discovery and development needs. Find the overview here.
  • Layered tissues with perfused tubules in the absence of artificial membranes form the heart of our permeability and transport science. Study cell interactions, permeability, absorption, transport, and transcytosis without physical barriers.

  • Co-culture layered & structured tissues without artificial membranes with perfect imaging, to study barrier-free cellular interactions, cell-cell signaling, and migration.

  • Evaluate the effect of chemotactic triggers or cells on the migration of cells through an extracellular matrix.

  • Membrane-free microvascular formation and growth through an extracellular matrix (ECM).

  • The missing link in tissue culture: add perfusable human vasculature to your tissue models, and recreate sophisticated microenvironments with OrganoPlate® Graft.

  • OrganoPlate® enables you to study relevant 3D tissue biology by incorporating perfused tubules, co-culture, and full control over the tissue microenvironment. Find the overview of applications here.

  • Visit our Knowledge Center to get up to speed with 3D tissue culture and to learn how OrganoPlate® supports your research needs.

    Read our publications, application notes, watch our webinars, or check out the supporting protocols and brochures. All compiled for you, by our scientists.

  • Get inspired by peer-reviewed publications of our scientists, partners, and customers around the globe.

  • Get inspired by research done by our scientists, partners, and customers around the globe.

  • Giving you some food for thought. Read our blogs to learn more about 3D tissue culture, research backgrounds, developments, and its future outlook.
  • Kickstart your experiments with the most sophisticated 3D tissue culture platform. Find out which training fits your 3D tissue modeling needs best.
  • Any support questions about purchasing, products, or 3D tissue culture and analysis? Get in touch with our experts.
  • Thinking of using OrganoPlate for your research? Request a quote for the product(s) of your interest.

  • Frequently asked questions answered by our experts. Find here the answer you're looking for.
  • Learn about our mission, vision, the history of the company, and find out what we mean with MIMETAS-do.
ENGLISH

Extracellular Matrix & 3D Tissue Models

What is extracellular matrix?

From a cell’s perspective, the matrix is everywhere.Scaffold by Ricardo Gomez Angel - unsplash.com In tissues and organs, the extracellular matrix (ECM) is made up by a 3D network of fiber-forming proteins, such as collagen, elastin, fibronectin, and glycosaminoglycans. It provides a physical scaffold for cells. Matrix macromolecules are synthesized and secreted by all cell types, a process that is influenced by cell-type specific regulatory mechanisms. As a result, the composition and structure of matrix macromolecules vary largely between tissues.

Why is ECM important for tissues?

The extracellular environment of cells plays a key role in many cellular processes, such as growth, migration, differentiation, survival, homeostasis, and morphogenesis. Cells embedded in ECM interact with the macromolecular network through surface receptors, affecting cellular function and behavior. In this way, ECM molecules provide mechanical, structural, and compositional cues that can drastically influence cell function. In addition, a variety of growth factors, cytokines, and chemokines are present in the ECM, often tethered to macromolecules, regulating tissue development and homeostasis.

Connected cultures: mimicking ECM in 3D tissue models

With ECM being part of all our body’s tissues, it makesNetwork by Jingyi Wang - unsplash.com sense to mimic its properties when developing 3D tissue models in vitro. For this purpose, a variety of 3D matrices are available. Such 3D matrix gels often feature a soft, tissue-like stiffness and mimic the ECM that is naturally present in tissues. Using 3D matrices for cell culture has several advantages, as it promotes cell adhesion and enables proper transport of gases, nutrients, and growth factors to the cells. This promotes cell survival, proliferation, and differentiation.

Gels made from ECM mixtures of natural origin, such as collagen and Matrigel®, are often used substrates for 3D cell culture. Recently, the need for more controllable gels has driven the development of various synthetic gels. The porosity, permeability, and mechanical characteristics of different gels vary, as they are designed to recapitulate the in vivo ECM of the specific tissues.

The viscosity of ECM gels increases with temperature, as a result of its physicochemical properties. Typically, cold ECM is pipetted in a culture chamber or plate, where it is allowed to set at a higher temperate. In an OrganoPlate®, liquid ECM gel is patterned into individual lanes, using capillary pinning PhaseGuide™ technology. Following gelation, additional ECM lanes can be added, or cells can be seeded as a tubule against the ECM gel.

Matrigel®
An often-used strategy to mimic ECM in tissue culture in the lab is by using Matrigel®: a gelatinous protein mixture that resembles the epithelial basement membrane. Matrigel® is secreted by Engelbreth-Holm-Swarm mouse sarcoma cells and consists of ECM, several growth factors, and heparan sulfate proteoglycan. It is known to contain relatively high levels of the basal membrane protein laminin. Depending on the type and dilution of Matrigel®, it can either promote or inhibit the proliferation and differentiation of cells. Its natural origin brings along batch-to-batch variation, which may complicate comparisons between experiments. Nevertheless, Matrigel® resembles the complex extracellular environment in many aspects, often resulting in increased physiological relevance of tissue models.

In the OrganoPlate®, a wide variety of Matrigel®-embedded tissue Pipetting ECM in the OrganoPlate®.cultures can be established and maintained. Culturing cells in Matrigel® in the OrganoPlate provides the cells with a growth scaffold that resembles their natural environment. In this 3D tissue culture platform, Matrigel® is particularly suitable for 3D neuronal cultures and (tumor) organoid cultures.

Collagen
Collagen is the main structural protein in the extracellular space in various connective tissues, as it is the main component of natural ECM. It is therefore often used as a matrix in 3D tissue culture. At MIMETAS, collagen-based cultures are used to establish vasculature-on-a-chip models, as collagen supports angiogenesis and blood-vessel-sprouting assays. Collagen is also highly suitable to establish other tube-based tissues in the OrganoPlate, such as kidney and intestinal models.

Synthetic hydrogels
Hydrogels are water-swollen networks of natural or synthetic polymers. Compared to natural ECM extracts, synthetic gels are highly customizable, as they can be modified for specific cultures by incorporation of different types of proteins, peptides, and other molecules. In this way, it is possible to incorporate specific cues to influence cellular function and behavior.

A publication in Nature by Gjorevski et al (2016), highlights the effects of different ECM properties on organoid culture. Based on their findings regarding stiffness and degradability of the ECM gels, the authors designed matrices, optimized for expansion, differentiation, and organoid formation. This demonstrates the potential of hydrogels as well-defined alternatives to animal-derived 3D matrices. The OrganoPlate® supports hydrogel-based tissue culturing, which offers highly customizable ways to mimic the tissue-specific extracellular environment in vitro.

Knowledge Center

References

  • Caliari, S. R., & Burdick, J. A. (2016). A practical guide to hydrogels for cell culture. Nature methods, 13(5), 405-414.
  • El-Sherbiny, I. M., & Yacoub, M. H. (2013). Hydrogel scaffolds for tissue engineering: Progress and challenges. Global Cardiology Science and Practice, 38.
  • Gjorevski, N., Sachs, N., Manfrin, A., Giger, S., Bragina, M. E., Ordóñez-Morán, P., ... & Lutolf, M. P. (2016). Designer matrices for intestinal stem cell and organoid culture. Nature.
  • Hughes, C. S., Postovit, L. M., & Lajoie, G. A. (2010). Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics, 10(9), 1886-1890.
  • Theocharis, A. D., Skandalis, S. S., Gialeli, C., & Karamanos, N. K. (2016). Extracellular matrix structure. Advanced drug delivery reviews, 97, 4-27.
  • Matrigel® is a registered trademark owned by Corning®.
  • Images: Scaffold by Ricardo Gomez Angel, Network by Jingyi Wang - unsplash.com