Sertoli Cell-Induced Reversal of Adult Rat Pancreatic Islet β-Cells into Fetal-Like Status: Potential Implications for Islet Transplantation in Type I Diabetes Mellitus

Abstract

Background

Clinical success of pancreatic islet allograft (TX) for the therapy of diabetes mellitus is hampered by several pitfalls, primarily including the restricted availability of donor tissue and the immune- and/or non-immune-related TX's early loss, with the latter not necessarily being prevented by the host's general immunosuppression. Finally, adult islet β-cells normally exhibit minimal proliferation capacity, which would not permit restoration of an eventually declining TX mass.

Methods

To address the limited β-cell growth capacity, we have examined whether in vitro co-culturing adult rat islets (I) with prepubertal homologous Sertoli cells (SC) would stimulate I β-cell expansion. SC-derived effects on the islets were studied in vitro, both morphologically (confocal laser microscopy) and functionally (glucose-stimulated insulin release). We have also preliminarily examined the in vivo impact of microencapsulated SC+I co-cultures on TX in diabetic mice.

Results

In vitro, we observed that SCs promoted significant β-cell replication, as I β-cell mitotic activity increased from 1% to greater than 8%, which coincided with the adult elements reversing into fetal-like status. This finding was coupled with significantly greater insulin release either in basal or in response to glucose, as compared with controls.

Conclusions

Addition of SC to islets promotes reversal of the adult β-cell elements into fetal-like conditions, thereby providing a new, potentially powerful tool that could significantly enhance the functional performance of islet TX in diabetic recipients.