Mitogen Synergy: An Emerging Route to Boosting Human Beta Cell Proliferation

Decreased number and function of beta cells are a key aspect of diabetes mellitus (diabetes), a disease that remains an onerous global health problem. Means of restoring beta cell mass are urgently being sought as a potential cure for diabetes. Several strategies, such as de novo beta cell derivation via pluripotent stem cell differentiation or mature somatic cell transdifferentiation, have yielded promising results. Beta cell expansion is another promising strategy, rendered challenging by the very low proliferative capacity of beta cells. Many effective mitogens have been identified in rodents, but the vast majority do not have similar mitogenic effects in human beta cells. Extensive research has led to the identification of several human beta cell mitogens, but their efficacy and specificity remain insufficient. An approach based on the simultaneous application of several mitogens has recently emerged and can yield human beta cell proliferation rates of up to 8%. Here, we discuss recent advances in restoration of the beta cell population, focusing on mitogen synergy, and the contribution of RNA-sequencing (RNA-seq) to accelerating the elucidation of signaling pathways in proliferating beta cells and the discovery of novel mitogens. Together, these approaches have taken beta cell research up a level, bringing us closer to a cure for diabetes.