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The biocompatibility of membranes aiming at being a part of a bioartificial pancreas has been tested. For that purpose, we have studied a polycarbonate membrane surface after its implantation in mini-pigs. The membranes were made hydrophilic by an argon plasma surface treatment followed by a dipping in a hydrophilic polymer solution. Two polymers were tested: polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC). To test their biocompatibility, an encapsulation device for pig Langerhans islets, with external membranes treated as described above, was implanted in different mini-pigs. The pigs received no further treatment. The devices were explanted after in vivo exposure and the membranes were analysed by XPS (x-ray photoelectron spectroscopy) and ToF-SIMS (time-of-flight secondary ion mass spectrometry). After this time, the substrate with the PVP or HPMC treatment was still detected on the different samples. The surface treatment signal, however, was attenuated. This is explained by the detection of other components partly covering the surface. XPS and ToF-SIMS analyses revealed the presence of biological molecules on the two faces of the membrane: the outside face in contact with the biological environment and the inside face in contact with the device. ToF-SIMS images show the inhomogeneity of the biological molecules on the membrane surface. In conclusion, biological molecules adhered to the encapsulation membrane surface after implantation but the surface treatments remained unaltered.

BACKGROUND & AIMS: Adult stem cells provide a promising alternative for the treatment of diabetes mellitus and end-stage liver diseases. We evaluated the differentiation potential of human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells. METHODS: Monocytes were treated with macrophage colony-stimulating factor and interleukin 3 for 6 days, followed by incubation with hepatocyte and pancreatic islet-specific differentiation media. Cells were characterized by flow cytometry, gene-expression analysis, metabolic assays, and transplantation for their state of differentiation and tissue-specific functions. RESULTS: In response to macrophage colony-stimulating factor and interleukin 3, monocytes resumed cell division in a CD115-dependent fashion, which was associated with a down-regulation of the PRDM1 and ICSBP genes. These programmable cells of monocytic origin were capable of differentiating into neohepatocytes, which closely resemble primary human hepatocytes with respect to morphology, expression of hepatocyte markers, and specific metabolic functions. After transplantation into the liver of severe combined immunodeficiency disease/nonobese diabetic mice, neohepatocytes integrated well into the liver tissue and showed a morphology and albumin expression similar to that of primary human hepatocytes transplanted under identical conditions. Programmable cells of monocytic origin-derived pancreatic neoislets expressed beta cell-specific transcription factors, secreted insulin and C peptide in a glucose-dependent manner, and normalized blood glucose levels when xenotransplanted into immunocompetent, streptozotocin-treated diabetic mice. Programmable cells of monocytic origin retained monocytic characteristics, notably CD14 expression, a monocyte-specific methylation pattern of the CD115 gene, and expression of the transcription factor PU.1. CONCLUSIONS: The ability to reprogram, expand, and differentiate peripheral blood monocytes in large q