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Presenter: Giacomo, Lanzoni, Miami, United States
Authors: Giacomo Lanzoni1,2, Roberta Costa1, Francesco Alviano1, Cosetta Marchionni1, Giuseppe Cavallari3, Laura Foroni4, Gianandrea Pasquinelli5, Roberto Rimondini6, Laura Bonsi1, Riccardo Casadei3, Francesco Minni3, Camillo Ricordi2, Luca Inverardi2, Gian Paolo Bagnara1
Pancreatic islets–derived Mesenchymal stromal cells can enter the pancreatic endocrine commitment but do not achieve consistent maturation
Giacomo Lanzoni1,2, Roberta Costa1, Francesco Alviano1, Cosetta Marchionni1, Giuseppe Cavallari3, Laura Foroni4, Gianandrea Pasquinelli5, Roberto Rimondini6, Laura Bonsi1, Riccardo Casadei3, Francesco Minni3, Camillo Ricordi2, Luca Inverardi2, Gian Paolo Bagnara1
Departments of 1Histology, Embryology and Applied Biology, 4Specialistic Surgical and Anaesthesiological Sciences, 6Pharmacology, University of Bologna, Bologna, Italy; 2Diabetes Research Institute, University of Miami, Miami, FL, United States; Departments of 3General Surgery and Transplantation, 5Hematology, Oncology, and Clinical Pathology, Division of Surgical Pathology, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
Mesenchymal Stromal Cells (MSC) can be derived from various organs, display a wide differentiation potential and appear to have trophic effects. They have been shown to promote islet survival and function and are thus attractive for diabetes treatments that may include composite transplants. Furthermore, MSC have been shown to give rise to islet cell-like clusters. Pancreatic islet-derived mesenchymal stromal cells (PI-MSC) may be more prone to commit to islet specific phenotypes due to their tissue derivation.
We isolated and expanded MSC from human pancreatic islets. Cell populations were characterized by flow cytometry and immunofluorescence. The differentiation potential toward mesenchymal and pancreatic endocrine cells was tested in vitro and in vivo after transplantation in streptozotocin-induced diabetic rats.
After expansion in Chang medium, pancreatic islet-derived stromal cells expressed MSCs markers: CD44+, CD73+, CD90+, CD105+, CD146 low+, CD14-, CD19-, CD34-, CD45-, HLA-DR-. The cells showed multidifferentiation potential toward adipocytes and endothelial cells; moreover, they differentiated towards endocrine lineages both in vitro and in vivo, increasing insulin levels and, to a higher extent, glucagon levels. Under our induction conditions, PI-MSC gave rise to cells with a mixed phenotype and incomplete differentiation. After transplantation in diabetic rats, a transient effect was evidenced by a lowering of glycemia levels and of water intake. Two weeks after xenotransplantation in the absence of immune suppression, glucagon- and insulin-expressing cells were detected in grafts. Cells coexpressing the pericytic marker CD146 and endocrine markers were observed.
PI-MSC seem to have the potential to enter the pancreatic endocrine commitment resulting in in vivo amelioration of blood glucose control in transplanted animals. Improvements in expansion and differentiation protocols will result in additional efficacy.
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