Tissue & Disease Modeling
Human Tissue Models Selected by the Endpoint
Most in vitro programs do not fail because the model was insufficiently complex. They fail because the model was never matched to the decision it was asked to support, or because the data arrived without the information needed to know how far it could be pushed.
ProNAMs builds and runs human-relevant tissue models under one operating standard: the endpoint defines the model, acceptance criteria are fixed before the study begins, and every dataset is delivered with the applicability domain that governs its use. The portfolio is organized by biological scale - what kind of tissue the question lives in - and by the class of decision each scale supports.
| Biological Scale | Model | Decision Supported | The Question It Answers |
|---|---|---|---|
| Barrier tissue | 3D Full-Thickness Skin | Efficacy and local safety; claim substantiation | Does the active reach the tissue and do what it claims? |
| Functional organ tissue | iPSC-Derived 3D Cardiac MPS | Organ-level liability and mechanism | Does the compound perturb function, and at what measured exposure? |
| Neural microtissue & secretome | iPSC-Derived 5-HT Hindbrain Microtissue | Target and biomarker discovery; response heterogeneity | What is the compound doing, and does the response depend on genetic background? |
The Case for Human-Based Approach Methodologies
Species differences are not a rounding error. Cross-species extrapolation is weakest exactly where it is most often relied upon: barrier lipid composition and irritation response, cardiac repolarization physiology, and the polygenic architecture of sporadic neurodegenerative disease. Most Alzheimer's models rest on single-gene familial mutations that do not represent the sporadic population; behavioral endpoints add a second translation gap on top of the first.
2D culture removes the variables under study. Monolayers lack a dermal–epidermal junction, tissue-level mass transfer, and the three-dimensional organization that shapes neuronal maturation and network formation. Unanticipated cardiotoxicity remains a significant cause of attrition, and cardiac liabilities discovered late are costly to resolve.
The regulatory environment has moved - with limits worth stating plainly. The FDA Modernization Act 2.0 removed the statutory requirement for animal testing in drug applications; it did not, by itself, validate any specific in vitro method. The 2022 ICH S7B/E14 Q&A sets out how non-clinical in vitro data can be positioned within cardiac safety assessment. OECD test guidelines define the framework for skin irritation and corrosion endpoints. We work to these frameworks and describe our alignment precisely, without representing investigative data as validated regulatory data.
Our Services
3D Full-Thickness Skin Model Services
A bilayered tissue reconstructed in vitro from human primary cells: fibroblasts established within a collagen scaffold to form the dermal compartment, keratinocytes established above it, with air–liquid interface culture driving full epidermal differentiation. The result is a stratified epidermis over a functional, fibroblast-populated dermis - including the dermal–epidermal junction that epidermis-only formats omit.
Applied to: anti-aging and firming efficacy, barrier function and repair, UV/pollutant/chemical damage models, mechanism of action, and bioactive ingredient screening. Pigmented, aged/photoaged, psoriasis and atopic dermatitis configurations are available, alongside a 3D corneal epithelium model for ocular endpoints.
Endpoints: histology (H&E, blinded scoring against pre-defined criteria), immunostaining, RT-qPCR, ELISA, TEER and permeability marker flux, structural protein quantification, and dimensionless suction-based mechanical parameters.
Where it stops: the model addresses local exposure. It carries no systemic metabolism, circulation, or adaptive immune component. Mechanical parameters support comparison between concurrently measured arms; they are not absolute values and are not comparable with in vivo measurements.
Explore 3D Full-Thickness Skin Model ServicesiPSC-Derived Hindbrain Microtissue & EV Screening
3D serotonergic hindbrain microtissues generated from defined human genetic backgrounds, analyzed together with the extracellular vesicles they secrete. Serotonergic neurons of the raphe nuclei degenerate early in Alzheimer's disease and are associated with neuropsychiatric symptoms - agitation, depression, sleep disturbance - that affect a large proportion of patients and remain poorly served therapeutically.
Applied to: target and biomarker discovery by comparative microtissue–EV proteomics, phenotypic screening, mechanism of action profiling, and multi-background comparison studies that ask whether compound response varies across donors.
Endpoints: serotonergic identity and fraction (TPH2, SERT, FEV/PET-1) characterized per batch, viability, synaptic markers, LC-MS/MS proteomics of both microtissue and EV compartments, and EV characterization aligned to the MISEV reporting framework - NTA, tetraspanin and negative markers, TEM morphology, with the isolation method disclosed.
Where it stops: a hindbrain-derived model addresses the serotonergic dimension of the disease. It does not address amyloid or tau pathology, which are forebrain phenomena requiring cortical or hippocampal models. EV markers identified here are discovery-stage candidates from culture supernatant, requiring independent validation in clinical samples before any diagnostic application; we describe this as candidate biomarker discovery, not liquid biopsy development. Statistical power is governed by the number of independent genetic backgrounds, not by microtissues per background.
Explore iPSC-Derived Hindbrain Microtissue & EV ScreeningiPSC-Derived 3D Cardiac MPS Evaluation Services
Human iPSC-derived cardiomyocytes assembled with cardiac fibroblasts and endothelial cells into 3D tissue, evaluated under static or perfused conditions. ProNAMs performs study design, differentiation, tissue preparation and characterization, data analysis and reporting; perfusion-based culture and instrumented recording are delivered through an established collaboration operating commercially available MPS platforms.
Applied to: proarrhythmic risk investigation, structural cardiotoxicity, cardiovascular disease modeling on gene-edited or disease-background lines, and direct perfused-versus-static comparison on matched tissues.
Endpoints: field potential (MEA), membrane potential and action potential duration by optical recording, calcium transient kinetics, contractile parameters by motion analysis, viability and sarcomeric organization - and LC-MS/MS quantification of compound concentration in the tissue compartment and perfusate.
Where it stops: throughput is low to medium; this is confirmatory and mechanistic work, not library screening. iPSC-derived cardiomyocytes remain distinguishable from adult ventricular myocardium, which constrains how repolarization and calcium data are read. Study duration is measured in days to weeks, so chronic cardiac safety is outside the window. We position the platform as investigative rather than as a validated regulatory assay.
Explore iPSC-Derived 3D Cardiac MPS Evaluation ServicesChoosing the Right Model
| Question Addressed | Start with the Model | Indicative Program Duration* | Not the Right Fit For |
|---|---|---|---|
| Does this topical active substantiate an efficacy or barrier claim? | 3D Full-Thickness Skin | ~10–14 weeks | Systemic exposure or metabolism endpoints |
| Does this compound show irritation, corrosion or repair effects on human skin? | 3D Full-Thickness Skin (with corneal model for ocular endpoints) | ~10–14 weeks | Formally validated submission-grade classification without prior scoping |
| Does this candidate perturb repolarization, conduction, calcium handling or contractility? | Cardiac MPS | ~4–8 months | Ranking a compound library |
| Is my 2D cardiac signal real, or a format artefact? | Cardiac MPS, perfused-versus-static with measured exposure | ~4–8 months | Establishing clinical predictivity without clinical comparator data |
| What pathways does my CNS candidate move, and in which donors? | Hindbrain Microtissue & EV | ~6–9 months (repository lines) | Amyloid/tau endpoints |
| Can I generate candidate CNS biomarkers from a human model? | Hindbrain Microtissue & EV | ~6–9 months (repository lines) | Clinically validated diagnostic markers |
* Indicative only, derived from the stage durations published on each service page and subject to design.
Programs frequently run staged across formats - higher-throughput work to narrow the set, then one of these platforms for mechanistic or confirmatory evaluation. We will advise on that sequence, including where the appropriate next step is not one of our services.
How An Engagement Runs
Ready to Scope a Study?
Tell us the decision the data has to support. We will tell you which model fits, what it can conclude, and where it stops.
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