Autoimmune and immune-mediated inflammatory diseases involve a combination of immune-cell activation, inflammatory signalling and changes within the affected tissue. In conditions such as rheumatoid arthritis, lupus, inflammatory bowel disease and inflammatory skin disorders, these responses can become persistent, leading to chronic inflammation and progressive tissue damage.
This makes preclinical modelling particularly important. Simple single-cell or single-endpoint assays can be useful, but they do not always capture the interactions between immune cells and tissue-resident cells that drive disease. For many drug discovery programmes, more physiologically relevant human in vitro models can therefore provide a better way to assess inflammatory responses and therapeutic activity.
As a specialist preclinical CRO, Cellomatics Biosciences develops bespoke human cell-based models for autoimmune and inflammatory disease research (https://cellomaticsbio.com/inflammation/). These range from monoculture and primary immune-cell assays through to multicellular co-cultures and more complex 3D systems.
Why human cell-based assays matter in autoimmune disease research
Although autoimmune diseases affect different organs, many share common biological mechanisms, including:
- inappropriate activation of T cells, B cells, monocytes and macrophages;
- excessive production of inflammatory cytokines and chemokines;
- abnormal immune-cell migration and tissue infiltration;
- disruption of epithelial or endothelial barriers;
- altered communication between immune and tissue-resident cells; and
- chronic inflammation leading to tissue remodelling and fibrosis.
For this reason, selecting the right cell based assay CRO and experimental model can be important when assessing the mechanism and efficacy of a new therapeutic candidate.
Cellomatics’ immunology platform includes macrophage-based assays, T-cell and B-cell assays, PBMC-based systems, flow cytometry, migration and adhesion assays (https://cellomaticsbio.com/immunology/). The company also has access to fresh primary ex vivo immune cells through on-site healthy-volunteer recruitment and can source healthy and diseased tissues and cells from a range of autoimmune and inflammatory conditions.
This allows studies to progress from straightforward immune cell assays through to more complex models incorporating both immune and disease-relevant tissue cells.
Rheumatoid arthritis: modelling immune and stromal cell interactions
Rheumatoid arthritis provides a good example of why multicellular human models can be valuable.
Within the rheumatoid joint, fibroblast-like synoviocytes interact closely with immune cells and contribute to the production of cytokines, chemokines, matrix-degrading enzymes and other inflammatory mediators.
Cellomatics has developed several rheumatoid arthritis models, including:
- primary healthy or disease-derived fibroblast-like synoviocyte monocultures;
- fibroblast-like synoviocyte and PBMC co-cultures;
- chondrocyte models; and
- more complex synoviocyte, chondrocyte and PBMC triple co-cultures.
These models can incorporate endpoints such as T-cell activation, cytokine release, oxidative stress and flow-cytometric analysis.
For researchers looking for a PBMC assay CRO, T cell assay CRO or macrophage assay CRO, these systems allow the immune component of rheumatoid arthritis to be investigated alongside relevant stromal cells rather than in isolation.
Cellomatics has also characterised macrophages derived from rheumatoid arthritis donors, measuring inflammatory mediators including IFN-γ, IL-1β, IL-6, IP-10, MCP-1 and TNF-α.
Patient-derived rheumatoid fibroblast-like synoviocytes have similarly been used to investigate therapeutic effects on IL-6, TNF-α, MMP-1 and MMP-3.
Cutaneous lupus: combining inflammation assays with cell migration
In autoimmune diseases such as cutaneous lupus erythematosus, the recruitment of immune cells into affected tissue is an important component of disease biology.
Cellomatics has developed a human keratinocyte-PBMC co-culture model in which cells can be stimulated with Poly I:C or IFNλ and treated with pathway inhibitors or neutralising antibodies. The system supports both cytokine profiling and functional chemotaxis measurements.
Inflammatory endpoints investigated within this model include CCL2, CXCL10, TNF-α, MMP-9, IFN-γ, GM-CSF, CCL3 and IL-6.
A functional cell migration assay can then determine whether modulation of inflammatory signalling also alters immune-cell recruitment. Cellomatics has demonstrated quantification of chemotaxis within this model following 24 hours of migration.
Combining inflammation assays with functional immune-cell migration therefore provides additional insight beyond cytokine measurements alone.
Scleroderma and fibrosis assays
Autoimmune disease can also lead to extensive tissue remodelling and fibrosis.
Scleroderma is a particularly important example, where persistent immune and inflammatory signalling contributes to activation of fibroblasts and excessive extracellular matrix deposition.
Cellomatics has developed human dermal fibroblast models using TGF-β and bleomycin stimulation to reproduce components of the fibrotic response.
These fibrosis assays can assess changes in genes such as TOP1, CTGF, MMP1, COL1A1 and ACTA2 using qPCR.
Protein-level measurements, including MMP1 and pro-collagen I A1, can also be incorporated using ELISA.
This provides a platform for investigating whether candidate therapeutics can modulate not only inflammatory signalling but also downstream fibrotic processes.
Inflammatory bowel disease: modelling immune-barrier interactions
Inflammatory bowel disease highlights another important feature of autoimmune and immune-mediated disease: the interaction between inflammation and tissue-barrier dysfunction.
Cellomatics’ IBD platform includes several levels of complexity, ranging from epithelial monocultures through to Caco-2/THP-1 co-cultures and primary human intestinal epithelial cells combined with PBMCs.
IBD is associated with increased pro-inflammatory immune responses, increased intestinal permeability and altered tight-junction organisation.
Accordingly, Cellomatics’ human cell based assays can incorporate complementary endpoints including:
- cytokine and chemokine release;
- tight-junction gene expression;
- TEER;
- FITC-dextran permeability;
- cell viability; and
- immune-cell responses.
The Caco-2/THP-1 co-culture model has demonstrated increased inflammatory mediator production following IL-1β/LPS stimulation and pharmacological suppression using reference anti-inflammatory compounds.
Primary intestinal epithelial cells can also be combined with PBMCs, enabling direct investigation of communication between the epithelial barrier and the immune system.
Autoimmune and inflammatory skin disease models
Inflammatory skin diseases (https://cellomaticsbio.com/psoriasis/) are another area where combining tissue-specific cells with immune cells can add biological relevance.
Cellomatics has developed models using:
primary human keratinocytes → keratinocyte/PBMC co-cultures → reconstructed human epidermis and 3D skin models.
For atopic dermatitis (https://cellomaticsbio.com/atopic-dermatitis/), primary keratinocytes can be stimulated using IL-13 and Poly I:C and inflammatory responses measured using multiplex assays.
Keratinocytes can also be co-cultured with freshly isolated PBMCs to investigate the interaction between inflammatory skin cells and the immune compartment.
More complex 3D cell culture systems using reconstructed human epidermis can provide an additional level of tissue relevance and allow investigation of gene-expression responses to therapeutic intervention.
Similar approaches are available for psoriasis, where IL-17-driven inflammatory biology can be assessed using cytokine profiling, proliferation and gene-expression endpoints.
These capabilities complement Cellomatics’ wider expertise in 3D cell culture, spheroid and organoid model development.
From immune-cell assays to complex human disease models
No single experimental system can reproduce every component of autoimmune disease.
The optimal model depends on the therapeutic target, mechanism of action and stage of drug development.
An early programme may begin with relatively simple and scalable human cell-based assays, for example:
PBMC assays | T-cell assays | macrophage assays | cytokine-release assays | chemotaxis assays | target-engagement assays
Once activity has been demonstrated, programmes can progress towards more complex disease-relevant systems incorporating tissue-specific cells, disease-derived donors and multicellular co-culture models.
Cellomatics’ broader capabilities include cell biology assays, molecular assays, phenotype-based imaging, analytical assays, contract cell culture and customised assay development.
The company also has expertise in developing complex humanised models, including 3D spheroid and organoid models.
This means that clients seeking an immune cell assay CRO, human cell based assay CRO, 3D cell culture CRO or bespoke preclinical CRO partner can select the level of model complexity appropriate for their programme.
Supporting autoimmune drug discovery with a specialist preclinical CRO
Autoimmune disease drug discovery requires models that capture more than a single inflammatory pathway.
Combining primary human immune cells, disease-derived cells, tissue-specific cells, inflammation assays, fibrosis assays and functional cell migration assays can provide a more comprehensive understanding of how a therapeutic candidate affects disease biology.
At Cellomatics Biosciences, our approach is to design the experimental system around the biological question.
From PBMC, T-cell and macrophage assays through to multicellular co-cultures and advanced 3D human cell models, our scientists develop bespoke preclinical studies to evaluate therapeutic efficacy, mechanism of action and disease-relevant biological responses.
For organisations looking for an experienced in vitro CRO or preclinical CRO specialising in human cell-based assays, Cellomatics can support programmes from early assay development through to more complex mechanistic and disease-relevant studies.
