Reversion of early- and late-stage β-cell dedifferentiation by human umbilical cord-derived mesenchymal stem cells in type 2 diabetic mice

Abstract

Background aims: The authors aimed to observe β-cell dedifferentiation in type 2 diabetes mellitus (T2DM) and investigate the reversal effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on early- and late-stage β-cell dedifferentiation.

Methods: In high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mice, the authors examined the predominant role of β-cell dedifferentiation over apoptosis in the development of T2DM and observed the reversion of β-cell dedifferentiation by UC-MSCs. Next, the authors used db/db mice to observe the progress of β-cell dedifferentiation from early to late stage, after which UC-MSC infusions of the same amount were performed in the early and late stages of dedifferentiation. Improvement in metabolic indices and restoration of β-cell dedifferentiation markers were examined.

Results: In HFD/STZ-induced T2DM mice, the proportion of β-cell dedifferentiation was much greater than that of apoptosis, demonstrating that β-cell dedifferentiation was the predominant contributor to T2DM. UC-MSC infusions significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In db/db mice, UC-MSC infusions in the early stage significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In the late stage, UC-MSC infusions mildly improved glucose homeostasis and partially reversed β-cell dedifferentiation. Combining with other studies, the authors found that the reversal effect of UC-MSCs on β-cell dedifferentiation relied on the simultaneous relief of glucose and lipid metabolic disorders.

Conclusions: UC-MSC therapy is a promising strategy for reversing β-cell dedifferentiation in T2DM, and the reversal effect is greater in the early stage than in the late stage of β-cell dedifferentiation.

Keywords: cell transplantation; mesenchymal stem cells; type 2 diabetes mellitus; β-cell dedifferentiation.