title: The impact of hyperglycemia and the presence of encapsulated islets on oxygenation within a bioartificial pancreas in the presence of mesenchymal stem cells in a diabetic Wistar rat model.
abstract: This study investigates the potential of bone marrow (BM-MSCs) versus adipose mesenchymal stem cells (AMSCs) to potentiate the oxygenation of encapsulated islets in a subcutaneous bioartificial pancreas. Oxygen pressures (inside subcutaneous implants) were followed in vivo (by electronic paramagnetic resonance) in non-diabetic/diabetic rats transplanted with encapsulated porcine islets or empty implants up to 4 weeks post-transplantation. After graft explantation, neoangiogenesis surrounding the implants was assessed by histomorphometry. Angiogenic properties of BM-MSCs and AMSCs were first assessed in vitro by incubation of the cells in hypoxia chambers, under normoxic/hypoxic and hypo-/hyperglycemic conditions, followed by quantification of vascular endothelial growth factor (VEGF) release. Second, the in vivo aspect was studied by subcutaneous transplantation of encapsulated BM-MSCs and AMSCs in diabetic rats and assessment of the cells' angiogenic properties as described above. Diabetic state and islet encapsulation induced a significant decrease of oxygenation of the subcutaneous implant and an increased number of cells expressing VEGF. AMSCs demonstrated a significantly higher VEGF secretion than BM-MSCs in vitro. In vivo, AMSCs improved the implant's oxygenation and vascularization. Diabetes and islet encapsulation significantly reduced the oxygenation of a subcutaneous bioartificial pancreas. AMSCs can improve oxygenation by VEGF release in hypoxia and hyperglycemia states.
authors.affiliation: Aspirant of FRS-FNRS, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vériter
authors.forename: Najima
authors.initials: N
authors.lastname: Aouassar
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Adnet
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Paridaens
authors.forename: Charlotte
authors.initials: C
authors.lastname: Stuckman
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jordan
authors.forename: Oussama
authors.initials: O
authors.lastname: Karroum
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.forename: Pierre
authors.initials: P
authors.lastname: Gianello
authors.forename: Denis
authors.initials: D
authors.lastname: Dufrane
mesh_terms: D000818:Animals; D021522:Bioartificial Organs; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005434:Flow Cytometry; D006943:Hyperglycemia / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A