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Pre-Clinical Testing → In Vitro and In Vivo Models for Pre-Clinical Studies

In vitro and in vivo models for pre-clinical studies

The efficacy and toxicity data obtained from pre-clinical in vitro and in vivo studies form the basis for clinical trials. For in vitro studies, immortalized cell lines, primary cells isolated from animal/human tissues, and stem cells are regularly used. For in vivo studies, laboratory mice and rats are routinely used. Animal disease models are often established in mice and rats by (a) introducing human diseases genes associated with the disease into the animal, or (b) a disease can be modelled via injecting the animal with a defined chemical. To ensure the relevance of the pre-clinical data to a human disease, in vitro and in vivo models have to be selected carefully.

A comparison between human primary cells and cell lines

    Human Primary Cells   Cell Lines
Culture   requires special media or additives (e.g., growth factors);
low-serum or serum-free media/standardized culture conditions;
culture conditions need to be adjusted for each cell type 		  standard media;
standard culture conditions
Handling   require more cell culture skills, careful planning, and are sensitive to mistreatment   easy to work with, easy to keep alive
Costs   higher   lower
Cell availability   limited   unlimited
Senescence   cells have limited self-renewal   cells can be grown and expanded over longer periods of time
Identity   donor characteristics are defined, cells retain the characteristics of the tissue of origin   questionable, misidentification possible
Reproducibility of results   lower, donor-to-donor variations need to be considered   higher, uniform cell type
Ethics   ethical regulations associated to the use of human tissue have to be considered   no need of human tissue
Morphology   show healthy cell morphology   loss of polarity, lack of key morphology features
Phenotype   maintain original phenotype for a limited number of passages depending on cell type and culture conditions   changes in phenotype (need to be validated!), functional alterations
Genome   genetically stable   altered genomic content
Contaminations   general contamination, cross-contamination with other cells, mycoplasma contamination, endotoxins need to be tested, antibiotics can influence cell metabolism   general contamination, cross-contamination with other cells, mycoplasma contamination, antibiotics can influence cell metabolism
Relevance in vivo   high   low (some cell lines show only marginal similarity to original primary cell phenotype)
Quality standards   standardized quality control and documentation is necessary   phenotype needs to be validated

Source: https://www.promocell.com/f/2019/10/Table_Human-primary-cells-and-cell-lines_0.jpg

Some examples of animal models

  1. APP/PS1 mouse model of Alzheimer’s disease, https://www.alzforum.org/research-models/appps1
  2. MPTP mice model of Parkinson’s disease, https://www.nature.com/articles/nprot.2006.342