Tracing the Fate of Cytokeratin 19+ Cells During Beta Cell Regeneration Stimulated by Multipotent Stromal Cell-Secreted Effectors
Abstract
Human bone marrow-derived multipotent stromal cells expanded under Wnt pathway stimulation secrete beta cell-regenerative factors collected as conditioned media (Wnt+ CdM). We used the cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage tracing mouse to observe CK19+ cell conversion to insulin+ beta cells following intra-pancreatic injection of Wnt+ CdM. Tamoxifen treatment in mice induced labelling of CK19+ ductal and acinar cells with tdTomato and streptozotocin (50 mg/kg/day x 5 days) induced hyperglycemia. Injection of Wnt+ CdM preserved beta cell mass, reduced non-fasted blood glucose levels, and improved glucose tolerance over a 28-day period compared to controls. Insulin+/tdTomato+ cells in mice given Wnt+ CdM were increased, suggesting a small percentage (<5%) of regenerated beta cells may have originated from CK19+ ductal or acinar cells.