IMG-1 Activates and Mobilizes Insulin-Producing Islet Progenitor Cells (CD133+/Insulin+) In Vitro

Abstract

IMG-1 is a novel therapeutic for the treatment of types 1 and 2 diabetes that may have islet regenerative properties. 300 islets isolated from mouse pancreases were cultured in standard media with IMG-1 (0.5µg/mL) and compared with control non-treatment. Within 24 hours, the IMG-1 treated islets became smaller (less clustered) and islet cells appeared to actively migrate away from the clusters. Control islets maintained their clustered morphology and did not show any evidence of cell migration. Three days after IMG-1 treatment, there were both free-floating and attached cells in the culture. The free-floating cells were 30% viable and the attached cells and leftover islets were 85% viable. In contrast, control islet cultures had neither free-floating nor attached cells although islet clusters looked healthy (cell viability >90%). By day 10 of IMG-1 treatment, islet clusters were few in numbers (<10%), no free-floating cells remained, and the attached cells appeared to form colonies. Total cell viability was >90%. Control cells still had no migration or attachment, although within the islet clusters cell viability remained around >90%. At 25 days, islet cells from both cultures were fixed and stained for the progenitor cell marker, CD133, and insulin. IMG-1 treated colonies were 75% insulin-positive by immunohistostaining. Furthermore, these cells were 70% CD133-positive with 60% of the culture being CD133/Insulin double-positive. In contrast, non-treated islets were 90% insulin+ cells, but <5% CD133+ and <5% double positive (CD133/insulin). IMG-1 has a novel effect on islets and induces the activation and migration of islet cells out of the islet. These cells form colonies of CD133/insulin double-positive cells that putatively represent activated beta-cell progenitor cells that can be used to regenerate damaged islets. Disclosure R. Bottino: None. J.B. Pollett: Employee; Self; Imagine Pharma. N. Thai: Board Member; Self; Imagine Pharma. M. Trucco: None.