Generation of human iPSC-derived beta cells to study the pathogenesis of type 1 diabetes and screen drugs in vitro

Pros, cons & Future potential

These cells present some advantages over primary or clonal human beta cells:

• -They can be generated on-demand from iPSCs, contrary to primary human islets that are much less readily available and are often isolated from older donors;
• -It is possible to generate iPSC from somatic cells obtained from T1D patients, which will allow the study of molecular mechanisms underlying diabetes-associated SNPs (single nucleotide polymorphisms);
• -They represent a valuable tool for the screening for new drugs that may protect beta cells against cytokine-induced cell death in early T1D;
• -They express receptors for the pro-inflammatory cytokines IL-1β, IFNγ, and IFNα and respond to these cytokines—particularly to IFNγ + IL-1β - similarly to adult human islets, the “golden standard” in the field.

At the end of the differentiation process, the beta cells are not yet fully mature, and secrete less insulin than adult beta cells.

There are major efforts by different groups to improve the differentiation process, and it is highly probable that in the near future it will be possible to achieve iPSC-derived beta cells with a function that is closely similar to adult beta cells.

iPSC-derived islet cells may become also a valuable tool for the screening of new drugs to protect beta cells against cytokine-induced cell death in early T1D.