Transplantation of tissues enclosed within a membrane device designed to protect the cells from immune rejection (immunoisolation) provides an opportunity to treat a variety of disease conditions. Successful implementation of immunoisolation has been hampered by the foreign-body reaction to biomaterials. We screened a variety of commercially available membranes for foreign-body reactions following implantation under the skin of rats. Histologic analysis revealed that neovascularization at the membrane-tissue interface occurred in several membranes that had pore sizes large enough to allow complete penetration by host cells (0.8-8 microns pore size). When the vascularization of the membrane-tissue interface of 5-microns-pore-size polytetrafluoroethylene (PTFE) membranes was compared to 0.02-microns-pore-size PTFE membranes, it was found that the larger pore membranes had 80-100-fold more vascular structures. The increased vascularization was observed even though the larger pore membrane was laminated to a smaller pore inner membrane to prevent cell entry into the prototype immunoisolation device. This significantly higher level of vascularization was maintained for 1 year in the subcutaneous site in rats.

Immunoisolation of allogeneic cells within a membrane-bound device is a unique approach for gene therapy. We employed an immunoisolation device that protects allograft, but not xenograft, cells from destruction, to implant a human fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG-human factor IX retroviral vector, and expressing 0.9 microg/10(6) cells/day in vitro, were implanted in rats (four 40-microl devices, each containing 2 x 10(7) cells, two subcutaneously, two in epididymal fat) and in mice (two 20-microl devices, each containing 2 x 10(6) cells, subcutaneously). Plasma factor IX levels increased for 50 days, reaching maxima of 203 ng/ml (rat) and 597 ng/ml (mouse), and both continued at greater than 100 ng/ml for more than 140 days. A clone derived from the transduced cells, making 5 microg of factor IX/10(6) cells/day, was implanted within a device (one 20-microl device containing 2.5 x 10(6) cells), or without a device (1 x 10(7) cells implanted freely), either subcutaneously or in epididymal fat. The freely implanted cells expressed transiently, reaching more than 100 ng/ml in each site by day 4, but dropped to zero by day 20 (subcutaneous) or day 90 (epididymal fat). In devices, levels gradually increased to 100 ng/ml (subcutaneous) or 300 ng/ml (epididymal fat), remaining high for more than 100 days. These results show long-term, high-level expression of a human protein: (1) when cells are implanted within a cell transplantation device, but not when the cells are freely implanted, and (2) from a transgene driven by a viral promoter. An alloprotective device will enable the use of cloned cell lines that can be subjected to stringent quality control assessment that is impossible to achieve with autologous approaches.

No abstract

Aneurysms treated with first-generation Matrix coils showed the greatest degree of coil compaction and aneurysm recurrence on the final angiographic evaluation. Aneurysms treated with first-generation Matrix coils showed enhanced thrombus organization and absence of vascular clefts at the aneurysm neck that were markedly different from those treated with bare platinum coils or a combination of GDC and Matrix coils.

No abstract