I'm trying to assess the utility of various in vitro assays/models, and I'm looking for *general thoughts/opinions* here. Elsewhere, I'm looking at the specifics of modelling the brain, modelling nanmomaterial-blood interactions, modelling cell transplantation etc.
I suspect each aspect of each model would need to be tested, and then the data compared to whatever in vivo data is available (if any; it may be incomplete, or rely on surrogate outcomes/biomarkers).
E.g. for a white blood cell (WBC) in vitro model: are WBC responses to immunosuppressive agents in vitro, identical to responses in vivo? You'd presumably have to measure the levels of lots of cytokines, in vitro and in vivo, and some may correlate better than others. (also morphological, motility, toxicological assays, etc.)
I presume that you can only conclude that (this specific) in vitro WBC assay is a good model of (this specific) cytokine release in response to (this specific) immunosuppressive agent.
Strictly, you shouldn't extrapolate from this to assume that, say, apoptosis or chemotaxis in this model would also be representative of in vivo, but are there any standardised approaches to this kind of vitro/vivo comparison?
Have any rules for generalisation/extrapolation emerged? (e.g. if the in vitro secretome of a model is representative of in vivo, can we expect proliferation or apoptosis to also be representative of in vivo? Or is every element distinct?)
I'm sure most models work well for some aspects, but not others (e.g. rodent models vs human). Is there any database where failed/predictive applications of models are reported/collected?
Is there any database comparing (specific) cell lines with primary cells and/or in vivo data, for various assays?
I appreciate that this is broad and woolly, but I thank you for any comments on this.
The validation of in vitro models to "mimic" in vivo ones is a really difficult issue. In general is assumed that for a specific process studied (for example eye irritation, skin irritation, corrosion, contact allergy, and so) an only in vitro model would probably not be sufficient.
In Europe the European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM; http://ihcp.jrc.ec.europa.eu/our_labs/eurl-ecvam) is the organism that receive proposed alternative methods which reduce, refine or replace the use of animals for safety testing and efficacy/potency testing of chemicals, biologicals and vaccines. This validation process implies several steps and different organisms and last several years. In USA the responsible is ICCVAM (The Interagency Coordinating Committee on the Validation of Alternative Methods, http://iccvam.niehs.nih.gov/). Both organisms have databases with the protocols of validated methods, Advisory and Consultation Bodies, comments and recommendations. Another interesting site is AltTox. Org (http://www.alttox.org/about/), devoted to the development of alternative methods to toxicological studies.
When developing an in vitro model this should be mechanistically based on the in vivo process, scientifically supported and based on well-known responses described in vivo in front of a battery of chemicals and/or products. The comparison of responses in vivo and in vitro is a crucial parameter and ideally the in vitro data should be compared with human data. However, comparisons are generally performed with the results obtained using animal models.
As you see, the development of in vitro models is not a mere question and for this reason very few assays have been nowadays being validated and adopted. On the other side, it is an interesting way to deep into the physiological, pharmacological and toxicological mechanisms and thus to increase our scientific knowledge.
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