Mimicking nature-made beta cells: recent advances towards stem cell-derived islets.

PURPOSE OF REVIEW

Stem cell-derived islets are likely to be useful as a future treatment for diabetes. However, the field has been limited in the ability to generate β-like cells with both phenotypic maturation and functional glucose-stimulated insulin secretion that is similar to primary human islets. The field must also establish a reliable method of delivering the cells to patients while promoting rapid in-vivo engraftment and function. Overcoming these barriers to β cell differentiation and transplantation will be key to bring this therapy to the clinic.

RECENT FINDINGS

The ability to generate stem cell-derived β-like cells capable of dynamic glucose-responsive insulin secretion, as well as β-like cells expressing key maturation genes has recently been demonstrated by several groups. Other groups have explored the potential of vascularized subcutaneous transplant sites, as well as endothelial cell co-transplant to support β cell survival and function following transplantation.

SUMMARY

The generation of stem cell-derived islets with dynamic glucose-responsive insulin secretion has brought the field closer to clinical translation, but there is still need for improving insulin content and secretory capacity, as well as understanding the factors affecting variable consistency and heterogeneity of the islet-like clusters. Other questions remain regarding how to address safety, immunogenicity and transplantation site moving forward.