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Cell models

In vitro therapy development

Cell models are often the first step for therapy development. This step is called in vitro (‘in glass’ referring to the glass culture dishes that were used in the past). For DMD, usually muscle cell cultures are used. Compounds are tested in cells to show their mechanism of action, i.e. can they induces the expected changes on cell signalling, protein production, growth or differentiation. Furthermore, it gives an indication of the toxicity of the compound, i.e. do the cells survive?

Cell models

Cells are either derived from healthy persons or from patients, depending on the specific purpose. Muscle fibres are ‘postmitotic’, meaning that they cannot proliferate. However, muscle tissue also contains ‘satellite cells’, i.e. the muscle stem cells that are activated upon muscle damage, proliferate and repair the damage. These satellite cells can be isolated from a muscle biopsy and cultured in dishes. Alternatively, cells are isolated from a skin biopsy and then converted into muscle cells. Since cells have a limited expansion capability, they are often immortalised to create a cell line with unlimited proliferation capacity.

Nowadays also induced pluripotent stem cells are used frequently. Their advantage over muscle cells is that they have a huge expansion capacity; the disadvantage is, however, that they are modified, which may result in changes in their characteristics. Furthermore, these pluripotent stem cells need to first be differentiated into muscle-like cells, when used to study muscle diseases like DMD.

The advantage of cell models is that they are relatively cheap and it is easy to screen lots of compounds in a short time. The disadvantage is that they poorly represents the situation in the human body, where each tissue consists of a mix of cell types, and is also connected to other organs via e.g. blood and nerves.

European Neuromuscular Centre (ENMC)

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