Abstract
We described a bioartificial endocrine pancreas (Bio-AEP) which was constracted by placing pancreatic B-cell clusters (ICCs) trapped in a mixed matrix (mixture of extracellular matrix and agarose, containing maltose-carrying polystyrene and nicotinamide) in the center of a ring holder sandwiched between semipermeable membranes, which were shielded by silicone. In this experiment, nuclepore membranes of different pore size (0.2, 0.1, or 0.05μm), were employed as the semipermeable membrane, which provided a mechanical barrier between the endocrine pancreatic graft and the host's immune system. Streptozotocin (STZ)-induced diabetic rats were implanted with BioAEP containing mouse insulinoma B-cell (MINE-cells) clusters which respond to glucose stimulation. In STZ-diabetic rats with Bio-AEPs with a membrane of pore size 0.1μm, a return to normoglycemia was observed up to 20 weeks after implantation, without the use of any immunosuppressant. STZ-diabetic rats that had received Bio-AEPs with membranes of different pore sizes, did not remain normoglycemie for such a long period. The result indicate that the Bio-AEP with the 0.1μm pore size membrane should be useful for the implantation of xenograft pancreatic endocrine cells in diabetic animals and may open a new field in the therapy of human insulin-depended diabete mellitus.
