Permeability of filters used for immunoisolation

Immunoisolation of islets of Langerhans (islets) by their enclosure in a filter to isolate them from the host immune system following implantation is a particularly attractive method for bioartificial pancreas. The filter should have excellent semipermeability so that damaging components of the immune system cannot reach the implanted islets. In addition, oxygen and nutrients should be supplied at a sufficiently high rate to maintain tissue viability. In the present work we conducted in vitro diffusion studies of solutes with various molecular sizes through Nuclepore filters and an XM-50 ultrafilter, which have been preferentially used for immunoisolation. The high permeability of microsolutes was not reduced much by the presence of any filters, implying that oxygen and nutrients could be effectively supplied to living cells by diffusion even if enclosed in a filter. Since the predominant cause of allograft rejection is activation of cellular immunity by T lymphocyte, while humoral immunity including antibodies and complement proteins plays a major role in the rejection of xenografts, requirements for the semipermeability of filters highly depends on the donor of islet tissue. T lymphocytes with a diameter of about 10 microm can permeate through neither Nuclepore nor XM-50 filters because their pore size is less than 2 microm. Therefore all of the filters are anticipated to act as effective immunobarrier for islet allografts. Although the XM-50 ultrafilter and 0.015-microm-diameter Nuclepore filter can sharply fractionate macromolecules in accordance with their size (around 50 kD) in a pressure-driven process such as ultrafiltration, these filters were found to lose the fractionation efficiency of macrosolutes in a concentration-driven process such as diffusion. In other words, neither the Nuclepore filters nor the XM-50 ultrafilter could prevent passage of immunoglobulin G in the diffusion process. This finding suggests that these filters cannot protect xenogeneic islets from the host immune system because biomacromolecules may permeate through these filters by the concentration-driven force.