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.

Biomaterials 2011 Sep 14;32(26):5945-56. Epub 2011 Jun 14.

Aspirant of FRS-FNRS, Belgium.

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.

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http://dx.doi.org/10.1016/j.biomaterials.2011.02.061DOI Listing
September 2011

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