CGI showing drug discovery using organoids

Predictive Insights for Advanced Cell Models in Drug Discovery

Predictive and Translational Insights for Advanced Cell Models in Drug Discovery

Advanced 3D and iPSC-based cell models offer new, more effective opportunities to streamline lengthy drug discovery and screening processes and develop patient-specific, personalized therapies (treatments). This is due to their ability to better predict how a drug or drug candidate will interact with human cells and tissues, providing deeper, more physiologically relevant insights about potential off-target effects, drug functionality or toxicity for humans. 

As organoids - especially patient-derived organoids (PDOs) - retain morphological and molecular characteristics of the tissue/ tumor of origin, they are increasingly being used as in vitro drug development models. Spheroids – which are less complex but still possess 3D cell characteristics – also provide more advanced research models and a more biologically relevant environment for testing new and existing drug candidates.

Human-induced pluripotent stem cells (iPSCs) have emerged as effective sources for drug discovery and development of novel, regenerative therapies due to their nearly limitless reprogramming capabilities into several patient-specific somatic cell types.

Sartorius offers translational research tools for the generation and characterization of these advanced cell models, helping researchers select the right drug candidate early in the pre-clinical process by addressing key challenges such as:

  • Replacing cancer cell lines which accumulate additional mutations over time
  • Reducing animal models which do not fully reflect genetic characteristics of human cancers
  • Monitoring 3D cultures and structures objectively
  • Lack of validated protocols for reproducible well-to-well organoid formation
  • Need for sophisticated, quantitative analytical methods for characterization of 3D cell models

Solutions for Advanced Cell Models in Drug Discovery

RUO Cytokines Cell Culture vials

RUO Growth Factors and Cytokines

Cytokines and growth factors are key immune system signaling molecules that regulate immune responses, inflammation, cell growth, and differentiation. Their research has advanced our understanding of immune-related diseases and led to the development of targeted therapies and vaccines.

Sartorius produces high-quality, recombinant cytokines and growth factors for research purposes, free from animal-derived components. These rigorously tested products ensure reliable results, consistent supply, and meet the highest purity and efficacy standards, with ISO9001-certified quality management.

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Classical Media, Reagents and Supplements

Sartorius media, reagents and supplements are designed to support the growth and maintenance of a variety of cells and cell lines while meeting the highest quality standards. Each lot is manufactured under a strictly controlled process according to a Product Master Record for lot-to-lot consistency. 

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Incucyte® Live-Cell Analysis System

The Incucyte® Live-Cell Analysis System enables real-time live-cell analysis directly inside your incubator.

The powerful end-to-end platform offers the ability to kinetically visualize and quantify formation and growth of organoids cultured in Matrigel® domes as well as to assess the impact of treatments on organoid growth and morphology.

Incucyte® software makes the process of acquiring, viewing, analyzing and sharing images of living cells easier than ever before.

  • 3D cell model analysis: Organoid assays
  • Assessment of the impact of treatments on organoid growth and morphology
  • Evaluation of mechanisms of action using real-time morphology measurements

Explore Incucyte® Organoid Assays      View Application Note

Figure 2 - Distinguish between cytotoxic and cytostatic mechanisms of action using label-free measurements. Hepatic fragments were embedded (0.5K cells/well) in 50% Matrigel® and allowed to form organoids (3 days) prior to treatment. Brightfield images taken 2 days post treatment show compound-specific effects on organoid size and morphology. Concentration response curves (CRCs) of the area under the curve (AUC) analysis of area, eccentricity and darkness demonstrated differential profiles of cytotoxic (staurosporine and cisplatin) and cytostatic (fluorouracil) mechanisms of action. Data were collected over a 96-hour period at 6-hour intervals. Each data point represents mean ± SEM, n = 3 separate test occasions.

iQue® Advanced Flow Cytometry Platform

The iQue® Advanced Flow Cytometry Platform is a high-throughput suspension cell and bead analysis platform with a patented sampling method allowing for rapid sample acquisition for actionable results. In conjunction with the validated suite of iQue® T cell characterization kits and Forecyt® software, it enables broad in vitro characterization of a drug’s effect on killing in 3D tumor models.

iQue® is the fastest way to generate high-content data from small samples, making it ideal for screens where cells are precious or limited in number.

  • Evaluation of T cell response in advanced 3D tumor models
  • Pharmacological readouts, (i.e., E50 values)
  • Immune cell phenotype and function in advanced cell models

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View Application Note

Figure 2 - Note. BT474 spheroids were formed in ULA plates for 72 hours before Incucyte® Cytolight Rapid Green labeled PBMCs (5:1 effector-to-target ratio (E:T)) and CD3/CD28 Dynabeads™ were added for 24 hours. (A) Incucyte® images used to validate the washing protocol for separation of non-infiltrated immune cells from the spheroid and TILs. (B) Spheroids and TILs were dissociated to a single cell suspension and analyzed using the iQue® Human T Cell Activation Kit. Plate view shows individual well plots of side scatter (SSC) vs. CD3 with gates highlighting the number of CD3 positive TILs per iQue® sip from each well. Each column represents a different Dynabead™ density (n = 4). An outlier (highlighted in red) was excluded from subsequent analyses. (C) and (D) Activation marker expression comparison between the non-infiltrated and infiltrated T cells.

Cell Selection Retrieval instrument cellcelector flex

CellCelector Automated Cell Selection and Retrieval Platform

The CellCelector Flex Platform is a fully automated cell imaging and picking system developed for screening, selection and isolation of single cells, clusters, spheroids and organoids as well as single-cell clones and adherent colonies. 

  • Automated scanning, detection and gating of complex 3D structures
  • Organoid transfer with exceptionally low (1 μL) injection volumes of surrounding media into either 100% hydrogel, liquid media or any other medium
  • Successful embedding of spheroids and organoids in 100% Matrigel® into plates with or without cell culture membranes

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An open box of Sartorius Microsart ATMP Sterile Release and its contents

Microsart® Mycoplasma, Bacteria and Fungi Rapid qPCR Test Kits

Testing cell cultures for microbial contamination on a regular basis ensures culture performance and parameters remain consistent and reproducible.

Microsart® Mycoplasma, Bacteria and Fungi qPCR kits offer rapid, reliable and easy-to-use solutions for microbial contamination control in compliance with international guidelines. Get results in just three hours!

The combination of speed, accuracy and efficiency provided by the Microsart® Mycoplasma, Bacteria and Fungi qPCR kits provides peace of mind during your cell culture processes. These comprehensively validated kits are highly sensitive and offer broad range microbial detection, consisting of an efficient DNA isolation protocol, and followed by a real-time PCR assay using the Microsart® ATMP Bacteria/Fungi/Mycoplasma kit.

  • Accurate results in just three hours
  • Detects a broad range of bacteria and fungi
  • Highest level of qPCR specificity

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The Progress and Promise of iPSCs

Check out this video to learn about the history and application of iPSCs as well as the critical steps in an iPSC R&D workflow.

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Sartorius Solutions for Advanced Cell Models in Drug Discovery Provide:

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In-depth analysis of drug effects

Perform real-time, multiparametric analysis of organoids to better predict therapeutic outcomes using the Incucyte® Organoid Analysis Software Module. The iQue® Advanced Flow Cytometry Platform facilitates quick, multi-parameter analysis, enabling broad in vitro characterization of a drug’s effect on killing of tumors to be profiled in minimal time.

Lab-tested protocols

Simple, ease-of-use workflows from start to finish to support high-quality image and data acquisition as well as unbiased analysis. Deliver robust data suitable for pharmacological analysis.

Automation for increased productivity

With Incucyte® Organoid and Spheroid Assays you can automatically acquire, analyze and graph thousands of images (from up to six 96-well plates in parallel) and get answers faster. Automated image acquisition and analysis tools provide a ”set up and walk away” experience. View images remotely to monitor experimental progress and analyze in real time for rapid decision-making.

CellCelector enables automated workflows for high-throughput selection and picking of complex 3D structures.

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Featured Resource for Advanced Cell Models in Drug Discovery

Organoids in Drug Discovery eBook
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Organoids in Drug Discovery

How advanced live-cell analysis platforms allow for real-time monitoring of cell health, behavior and morphology of complex models.

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Label-Free, Real-Time Live Cell Assays for 3D Organoids Embedded in Matrigel
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Label-Free, Real-Time Live Cell Assays for 3D Organoids Embedded in Matrigel®

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Poster

Quantify T Cell Response in 3D Tumor Spheroids Using Advanced Flow Cytometry and Live-Cell Analysis

PDF | 1.3 MB

Frequently Asked Questions

The Incucyte® Live-Cell Analysis System enables label-free morphology measurements and monitoring of organoids treated with different compounds over several days. Brightfield images visualize compound-specific effects on organoid size and morphology. In addition, multi-parametric quantitative measurements provide insights about cytotoxic and cytostatic cellular responses. 

The iQue® spheroid immune cell killing (ICK) workflow measures subset analysis and cytokines quantification to examine the activation, killing, exhaustion, and memory profiles of T cells during co-culture with single spheroids.

The workflows utilize the iQue® Advanced High-Throughput Flow Cytometer with associated suite of T cell characterization reagent kits, and validated spheroid washing and dissociation protocols to provide an end-to-end solution for the evaluation of T cell response in advanced 3D tumor models. 

No. Incucyte® 3D Tumor Spheroid and Organoid Assays offer an integrated turnkey solution to automatically monitor and quantify tumor spheroid | organoid formation, growth and health in real time inside your tissue culture incubator.

We recommend a combined iQue® Advanced Flow Cytometry and an Incucyte® Live-Cell Analysis approach for stem cell evaluation during cell line selection and differentiation. This streamlined workflow measures differentiation marker expression over time and support applications in research and drug discovery.

Recommended Application Note: Utilizing Advanced Flow Cytometry and Live-Cell Imaging to Evaluate iPSC Pluripotency During Cell Line Selection and Differentiation Procedures

The CellCelector platform is a unique and fully automated cell imaging and picking system developed for detection, selection and isolation of single cells, clusters, spheroids and organoids as well as single cell clones and adherent colonies.

It enables the gentle picking of a wide range of organoid sizes, ranging from 80 μm to 3.5 mm. Its additional applications are in single cell isolation (e.g. CRISPR Single Cell Cloning) and in stem cell research e.g. iPSC’s, where it ensures both the viability as well as the clonality of picked colonies while maintaining their pluripotent characteristics.

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