Exploring the Roles of Insulin and Insulinoma Cells in Keratinocyte Migration

We previously demonstrated accelerated wound healing in an in vitro wound healing model and in genetically diabetic mice using hydrogel-encapsulated rat insulinoma cells (RIN-m) [1]. However, the results were obtained with an insulinoma cell line. Since cancer cells can promote growth and resist apoptosis [2], we examined keratinocyte response to RIN-m derived cell lines that delivered insulin (RIN-5F) or somatostatin (RIN-14B), an insulin inhibitor, to confirm the role of insulin in the accelerated wound healing.

Commercial insulin or conditioned media collected at weekly time points from monolayer or polyethylene glycol diacrylate encapsulated RIN-m, RIN-5F, or RIN-14B cells were evaluated for insulin levels and ability to increase keratinocyte migration in an in vitro scratch model of wound healing.

Encapsulated RIN-5F cells released the most insulin at 8.9±3.633 ng/mL, RIN-14B cells were no different than media controls. Commercial insulin and RIN-5F accelerated keratinocyte migration similarly. There was no difference between media controls and RIN-14B conditioned media.

In light of no accelerated in vitro wound healing response when using insulinoma derived cells lacking insulin, combined with the accelerated response when using commercial or insulinoma derived insulin, we conclude that the insulin is responsible for the accelerated healing and not some unidentified characteristic of cancer cells.

1. Aijaz, Ayesha, et al. Tissue engineering part A 21.21-22 (2015): 2723-2732.
2. Arwert, E.N., et al., Nature Reviews Cancer, 2012. 12(3): p. 170-180.