Canonical Wnt signaling pathway contributes to the proliferation and survival in porcine pancreatic stem cells (PSCs).

Abstract

Pancreatic stem cells (PSCs) transplantation is a potential therapeutic approach to type 1 diabetes mellitus (D1M). However, before clinical use, there are some major hurdles to be faced that need to be comprehensively considered and given some potential solutions in vitro. Human PSCs are difficult to obtain and have a short replicative senescence. As an alternative, we instead established porcine PSCs; as insulin is highly conserved and physiological glucose levels are similar between human and porcine. In order to solve the problems during transplantation therapy, such as the need for an enormous amount of PSCs and good cell survival in overactive autoimmunity induced by reactive oxygen cpecies (ROS) in D1M patients, we utilized Wnt3a overexpression to activate the canonical Wnt signaling pathway in PSCs. We found that the expression of proliferation genes, such as c-Myc, was up-regulated as the downstream of β-catenin, which promoted the PSCs proliferation and made cell numbers to meet the transplantation needs. We also showed that activation of the Wnt pathway made cells more readily tolerate ROS-caused mitochondria injury and cell apoptosis, thus making cells survive in autoimmune patients. The present study provides a theoretical basis for cell transplantation therapy of diabetes.