Preclinical research is evolving rapidly, and staying ahead means embracing innovative tools that streamline processes and provide actionable insights. Multi-Organ-on Chip (MOC) assays, also known as microphysiological systems (MPS), are among the most exciting breakthroughs, offering unprecedented opportunities to replicate human biology more accurately than ever before. As part of our collaboration with TissUse, we are spotlighting four fully validated MPS assays you should consider integrating into your preclinical research workflows in 2025. Whether you aim to enhance predictive power, reduce development costs, or accelerate your drug development timelines, these assays can help you supercharge your preclinical research and pave the way for a smoother transition to clinical trials.
What are Multi-Organ-On Chip assays, and why should you incorporate them in your preclinical research?
Multi-Organ-on Chip (MOC), also known as microphysiological systems (MPS), are exactly what it sounds like – organ-on-chip systems that replicate key in vivo tissue environments, including blood flow, three-dimensional architecture, cell-cell interactions, and concentration gradients. MPS systems arise as an innovative tool in preclinical research testing, overcoming the limitations of both traditional 2D in vitro-based tools and in vivo rodent models by offering a platform that reliably replicates key biological processes and organ interactions, offering a more accurate representation of human biological responses.
This is of particular importance in preclinical research, where traditional drug testing that relies on rodent models often faces challenges due to species-specific differences in protein recognition and biological processes, limiting the accurate prediction of human responses. While at InnoSer we try to address and mitigate some of these issues by working with translational rodent models that express human-like features; fully-human-cell-based systems may provide a higher level of clinical predictivity.
MPS systems are increasingly relevant for investigating pharmacokinetics (ADME), and both primary and secondary organ toxicity making them an excellent addition to your in vivo studies. These systems not only enhance the predictive power of your drug testing, but they also align with the FDA’s Modernization Act 2.0, encouraging broader adoption of MPS technologies. In fact, many pharmaceutical companies are now integrating MPS assays into their research pipelines alongside FDA submissions, further accelerating the shift toward human-relevant preclinical testing.
While setting up MPS in-house can be costly, outsourcing these studies to experienced CROs, such as InnoSer and TissUse, provides you with a cost-effective solution to access validated assays and cutting-edge technology. If you are looking to enhance the predictive power of your preclinical workflows and bridge the gap between animal models and human studies, the following assays are worth exploring.
1. Discover the permeability of your compound with the Blood-brain-barrier Liver MPS Assay
Uses: study of BBB permeability, organ toxicity, metabolite neurotoxicity
Cell types used: Brain microvascular endothelial-like cells derived from induced pluripotent stem cells (iPSCs) or neural spheroids
Available readouts: TEER measurement (transendothelial/epithelial electrical resistance), brain/circulation ratio, IF staining, metabolite identification (e.g., glucose/lactate ratio), flow cytometry, gene expression (qPCR), liver metabolism
Complementary in vivo studies: in vivo toxicology profiling, in vivo PK/PD profiling, in vivo efficacy studies in neurodegenerative disease models (PD, AD, ALS etc.,) or neurological disorders
This 3-chip organ assay developed by TissUse combines brain microvascular endothelial-like cells derived and differentiated from induced pluripotent stem cells (iPSC), neural spheroids, and liver cells to mimic the dynamic interplay between the blood-brain barrier (BBB) and the liver. This assay provides you with in-depth understanding of how your compounds interact with the BBB, which is critical for studying neurotoxicity and drug permeability, suitable to be performed before in-depth in vivo studies are initiated.
Compared to traditional 2D cell culture insert models, the BBB-Liver MPS incorporates fluid-flow induced shear stress and interconnection with relevant organ models. In this case, the inclusion of the liver allows you to measure the liver-brain interconnection for e.g., by assessing the liver-induced metabolite permeation into the BBB. Compared to animal models, the MPS uses human cells to allow better emulation of human pharmacokinetics (PK) and dynamics (PD).
For more details on the experimental setup and validated data demonstrating the permeation behavior of atenolol and propranolol, which align with their BBB properties in vivo, refer to the paper by Koening et al., 2022. To conduct studies using the BBB liver assay, PK/PD profiling studies in vivo or efficacy studies in mouse models of neurodegenerative diseases, please contact the InnoSer team.
2. Test for Bone Marrow Toxicity using TissUse’s Bone Marrow MPS Assay
Uses: Bone marrow toxicity, dose-range finding studies, refining treatments/ dose scheduling
Cell types used: human mesenchymal stromal cells (hMSC), human bone marrow CD34+ cells
Available readouts: flow cytometry (full lineage cell output tracking), cytokine, glucose or LDH analysis
Complementary in vivo studies: in vivo toxicology testing, in vivo dose response studies
This 2-organ chip assay developed by TissUse’s overcomes the limitations of traditional 2D in vitro models for bone marrow toxicity by allowing you to measure and track mature lineage-specific cells rather than progenitors. While animal models do allow the measurement of blood cell lineages in vivo, BM assessment represents a terminal endpoint, requiring a large number of animals in each dose to acquire bone marrow toxicity data at multiple timepoints.
By using a two-organ microfluidic chip (Humimic Chip 2) combined with a 3D ceramic scaffold (hydroxyapatite), this system replicates the human bone marrow niche, allowing for a more accurate assessment of leukocyte development and hematological toxicity in vitro. This Bone-Marrow-on-Chip system utilizes human CD34+ hematopoietic stem cells and mesenchymal stromal cells which are co-cultured onto an MSC-seeded scaffold to study lineage differentiation. The microfluidic system circulates media, which is crucial for maintaining the bone marrow niche.
For more details, check out the paper by Cairns et al., 2023, or reach out to the TissUse team for specific information on this model. To test bone marrow toxicity in vitro using the bone marrow assay and/or in vivo, contact the InnoSer team for expert support.
3. Test Absorption and Metabolism using the Intestine, liver MPS Assay
Uses: Absorption, metabolism for systemic, oral and/or dermal routes, repeated dose substance exposure
Cell types used: human small intestine cells (EpiIntestinalTM: enterocytes, paneth cells, M cells, tuft cells, intestinal stem cells) and human liver spheroid hepatocytes (3D InSightTM)
Available readouts: Compound and metabolite kinetic profile, gene expression (qPCR)
Complementary in vivo studies: PK/PD profiling in vivo, ADM in vivo
This 2-organ-on-chip model replicates the biological diffusion-based absorption barrier and mimics the critical processes of drug absorption, metabolism, and hepatotoxicity. It integrates human-relevant transporter expression, first-pass metabolism in the intestine, the stem cell niche, and liver metabolism of absorbed nutrients and drugs.
By accurately predicting human drug metabolism and hepatotoxicity responses, this assay you with invaluable insights into how drugs are processed in the liver, offering a more reliable and human-relevant alternative for PK testing.
For detailed experimental setups and validation data of the human liver-intestine co-culture model, we invite you to refer to the publication by Maschmeyer et al., 2015. To explore further assistance, reach out to the TissUse team. For performing both in vitro and in vivo ADME profiling studies, reach out to the InnoSer team.
4. Perform in vitro ADME profiling using the Intestine, liver, kidney, neuro MPS Assay
Uses: ADME profiling, PBPK, first-path metabolism, primary & secondary organ toxicity
Cell types used: primary small intestine barrier on Transwell, iPSC-derived glomerular cells and proximal tubules lines, primary liver mu-tissue spheroids, iPSC-derived neuro glial spheroids
Available readouts: Compound and metabolite kinetic (ADME) profile
Complementary in vivo studies: PBPK profiling in vivo, ADME in vivo
This 4-organ-on-chip model integrates the kidney, liver, intestine, and blood circuit to measure key pharmacokinetic and pharmacodynamic processes, including excretion (kidney), metabolism (liver), distribution (blood circuit), and absorption (intestine).
The model consists of a pump, channels, chambers, and organ systems designed to mimic human physiological interactions. It operates on the principle of compartmentalization, where molecules are transported through different compartments, mixing instantaneously while ensuring mass conservation.
Validated with multiple currently approved drugs (e.g., Haloperidol, Carbamazepine), this model provides you with a reliable in vitro platform for assessing drug behavior in the human body. By mimicking the interactions between organs, this 4-organ system offers a more comprehensive view of how drugs are absorbed, distributed, metabolized, and excreted (ADME). It is particularly useful for PK testing and primary and secondary organ toxicity assessments.
To dive deeper into the experimental setup or validation data for the 4-organ-on-chip model, reach out to the TissUse team. For conducting both in vitro and in vivo ADME and PK testing, or assessing organ toxicity, the InnoSer team is available to provide support and expertise.
How InnoSer and TissUse aim to advance Preclinical Research Testing
TissUse’s development teams are dedicated to advancing innovative MPS/OoC models and are ready to collaborate with you on creating customized assays tailored to your specific needs. Complementing TissUse’s expertise, InnoSer provides streamlined compound testing through a range of validated assays, including those highlighted in this blog post.
Together, InnoSer and TissUse offer you comprehensive research solutions designed to streamline your drug discovery and development process. By leveraging cutting-edge human in vitro and in vivo models that closely mimic human biology, this partnership empowers you to bridge critical gaps in preclinical research. With our support, you can enhance the efficiency of your workflows, reduce development risks, and increase the likelihood of bringing successful therapies to market.