Pancreatic Endocrine Differentiation Potential and Immunomodulatory Properties of Different Postnatal Progenitors

Type 1 diabetes (T1D) is an autoimmune disease that affects insulin-producing beta cells in the pancreas. In T1D patients the immune system mistakenly attacks beta cells. Treatment with exogenous insulin is a life-saving intervention but it can cause serious adverse effects. Transplantation of cadaveric pancreas and isolated islets showed that beta cell replacement could treat T1D and prevent complications very effectively, but both strategies have important limitations. Stem cell-based strategies represent a promising way for the replenishment and preservation of beta cells. Certain types of stem and progenitor cells can be harnessed to generate insulin-producing cells for beta cell replenishment. Other types of stem/progenitor cells can be utilized to inhibit autoimmune mechanisms and rejection of transplanted beta cells. In this study, we investigated multiple stem and progenitor cells to better define their potential as cell therapies for T1D. We analyzed the potential of human amniotic epithelial cells (hAECs). hAECs can be recovered in large numbers from otherwise discarded placental tissues. hAECs are endowed with stemness characteristics and can inhibit immune attacks. We developed an in vitro model to generate 3D islet-like structures. We aimed at testing whether organization into 3D organoids was able to boost beta cell maturation. Subsequently, we tested the ability of differentiated hAECs to secrete c-peptide in response to different glucose concentrations. We then evaluated the immunomodulatory properties of hAECs before and after pancreatic endocrine differentiation. Moreover, we investigated the pancreatic differentiation potential of adult human endodermal progenitor cells from different anatomical sites. We studied cells isolated from human Brunner’s Glands, Biliary Tree and Main Pancreatic Duct. Endodermal progenitor cells were differentiated in a traditional 2D culture system and a co-culture system with Pancreas derived Mesenchymal Stromal Cells (PI-MSCs). Therefore, finally, we combined hAECs and PI-MSCs in an attempt to boost endocrine maturation and obtain islet-like organoids.