Stem cells as disease models

Using stem cells to model disease is a powerful and innovative approach to biomedical research. Stem cells are cells that have the ability to differentiate into various specialized cell types in the body. Thanks to this ability, researchers can generate cellular models of different diseases using stem cells and thus study the mechanisms underlying these diseases in greater depth, and this usually works by :

Obtaining stem cells from specific tissues or cell sources often depends on the use of biomarkers, i.e. specific molecules or markers present on the surface of stem cells. These biomarkers make it possible to target and selectively isolate stem cells from other cell types: CD34, a surface marker frequently used to isolate hematopoietic stem cells. The CD133 (Prominin-1) un marqueur utilisé pour identifier et isoler les cellules souches progénitrices et les cellules souches tumorales dans différents tissus.CD90 (Thy-1) a marker used to identify and isolate progenitor and tumor stem cells in various tissues SSEA-4 (Stage-Specific Embryonic Antigen-4) used to isolate human embryonic stem cells.

- Differentiation into pertinent cell types: Once obtained, the stem cells are differentiated into specific cell types related to the disease under study. For example, to study a neurodegenerative disease such as Parkinson's, stem cells could be differentiated into dopaminergic neurons, the cells affected in this disease.

- Disease modeling: Differentiated stem cells can be genetically modified to carry the specific genetic mutations associated with the disease researchers want to study. For example, for Huntington, an abnormal expansion of the CAG repeat in the HTT gene is responsible. For the cystic fibrosis, mutations in the CFTR gene are involved.

- Studying disease mechanisms: Once the disease model has been established, researchers can study the mechanisms underlying the disease by observing how diseased cells behave differently from healthy cells. These mechanisms can vary depending on the specific disease and the model cells used, for example for certain diseases there are several biomarkers to understand their mechanisms:

When modeling disease using stem cells, it is important to consider biological measures that can be used to assess disease status, disease progression or response to treatment. When using stem cells to model disease, biomarkers play a crucial role in characterizing and tracking cellular changes associated with disease. Here are some examples of biomarkers commonly used when modeling diseases with stem cells:

• Differential gene expression: By comparing gene expression levels between diseased and normal model stem cells, we can identify specific genes that are switched on or off in response to disease.
• Disease-specific proteins: Detection and quantification of disease-associated proteins in model stem cells can provide information on the cellular changes characteristic of disease.
• Cell differentiation markers : In disease models, stem cells can show abnormal or altered differentiation patterns compared to healthy cells, which can be used as a biomarker of disease.
• Metabolite levels: Specific metabolites may be present at abnormal levels in stem cells modelled on metabolic or other diseases.
• Cellular stress markers: Cellular stress markers such as chaperone proteins and heat shock proteins (HSP70, HSP90), reactive oxygen species (ROS) and cellular antioxidants (glutathion), inflammatory cytokines IL-6 (Interleukin-6) and TNF-alpha (Tumor Necrosis Factor-alpha).
• Epigenetic alterations: Changes in epigenetic motifs, such as the DNA methylation, can be used as biomarkers to identify specific epigenetic changes associated with disease.
• Enzymatic activity : In some diseases, enzyme activity may be altered, and this can be measured to characterize the disease.