The regenerative capacity of human muscle relies on a population of cells called satellites cells. Although many parameters may have an influence of the regenerative capacity, some of them can be monitored in vitro. However, models in vitro can only be indicative. We have set up along with partners 1 and 3 (University of Bonn, MRC) a model to evaluate the regenerative capacity of human satellite cells in vivo.
This model is based upon the injection of human myoblasts expanded in vitro into regenerating muscles of "humanized" mice (i.e. immunodeficient strains which do not reject human cells). This model has been used to monitor expression of genes that are not expressed in vitro, but only in matured fibres.
Using this model, we have confirmed the results obtained in vitro (see IP, former result), which is that the proliferation capacity is one of the parameters involved in the regenerative capacity of human myoblasts. However, we also established that long period of expansion in vitro are also detrimental to the regenerative capacity. This result applies to cell-mediated gene therapy and cellular therapy in general, where the expansion of cells is usually needed to obtain a sufficient number of cells of relevant therapeutic potential. The model can also be applied to searching myogenic potential among embryonic or adult stem cells.