Adult mesenchymal stem cells (MSCs) are an attractive therapeutic agent for the treatment of various diseases, due to three main characteristics:
These characteristics mean that MSCs have important applications in cell differentiation and gene regulation, gene therapy and transplantation, and cell-based screening assays such as those used in pre-clinical drug discovery.
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Due to their multilineage and proliferative potential, in vitro culture of MSCs allows you to easily generate a variety of different physiologically relevant cells for use in your research. This also provides a valuable method to study patterns of gene regulation and/or function during differentiation, which is not yet well understood. For example, delivering small interfering RNA (siRNA) into MSCs can be used to decrease protein expression to subsequently determine what the function of that protein is and what pathways are involved.
Genetic modification of MSCs is emerging as a promising immunotherapy. Genes of interest can be easily introduced into MSCs via viral and non-viral transfection methods to enable transgene expression. Transplantation of genetically modified, tissue-specific MSCs into patients can exert immunosuppressive effects or reinforce the immune process through the expression of anti-inflammatory cytokines.2 MSC-based immunotherapy is already showing great promise in treating a variety of diseases, including a range of cancers.3
The self-renewal ability of MSCs means that they can be used to generate large numbers of cells, which is an essential requirement for cell-based screening assays. The scalability of MSC-based assays means that they can be used in a variety of screening applications, ranging from screening biomolecules against known targets to identifying potential targets through siRNA screening.
The multilineage potential of MSCs also means that they can be directed towards a variety of disease-related drug discovery programs, including for cancer, obesity, diabetes, and central or peripheral nervous system disorders.
MSC-based screening assays have a key advantage over using cell lines. Cell lines can yield inconsistent results, because some drug targets may only be expressed at certain time points during lineage differentiation. As such, using primary MSC-based screening assays allows identification of small molecules through the various stages of the differentiation process.