This form of xenotransplantation treatment has the potential for sustained benefit in human type 1 diabetics.

In neurodegenerative disease and in acute brain injury, there is often local up-regulation of neurotrophin production close to the site of the lesion. Treatment by direct injection of neurotrophins and growth factors close to these lesion sites has repeatedly been demonstrated to improve recovery. It has therefore been proposed that transplanting viable neurotrophin-producing cells close to the trauma lesion, or site of degenerative disease, might provide a novel means for continuous delivery of these molecules directly to the site of injury or to a degenerative region. The aim of this paper is to summarize recent published information and present new experimental data that indicate that long-lasting therapeutic implants of choroid plexus (CP) neuroepithelium may be used to treat brain disease. CP produces and secretes numerous biologically active neurotrophic factors (NT). New gene microarray and proteomics data presented here indicate that many other anti-oxidant, anti-toxin and neuronal support proteins are also produced and secreted by CP cells. In the healthy brain, these circulate in the cerebrospinal fluid through the brain and spinal cord, maintaining neuronal networks and associated cells. Recent publications describe how transplanted CP cells and tissue, either free or in an immunoprotected encapsulated form, can effectively deliver therapeutic molecules when placed near the lesion or site of degenerative disease in animal models. Using simple techniques, CP neuroepithelial cell clusters in suspension culture were very durable, remaining viable for 6 months or more in vitro. The cell culture conditions had little effect on the wide range and activity of genes expressed and proteins secreted. Recently, completed experiments show that implanting CP within alginate-poly-ornithine capsules effectively protected these xenogeneic cells from the host immune system and allowed their survival for 6 months or more in the brains of rats, causing no adverse effects. Previously reported evidence demonstrated that CP cells support the survival and differentiation of neuronal cells in vitro and effectively treat acute brain injury and disease in rodents and non-human primates in vivo. The accumulated preclinical data together with the long-term survival of implanted encapsulated cells in vivo provide a sound base for the investigation of these treatments for chronic inherited and established neurodegenerative conditions.

Previously a strategy for monitoring of pigs intended for cell transplantation was developed and successfully applied to several representative herds in New Zealand. A designated pathogen-free (DPF) herd has been chosen as a good candidate for xenotransplantation. This herd has previously tested free of infectious agents relevant to xenotransplantation and we present here an in depth study of porcine endogenous retrovirus (PERV) transmission. A panel of assays that describes the constraints for the transmission of PERV has been suggested. It includes a) infectivity test in coculture of DPF pig primary cells with both human and pig target cell lines; b) RT activity in supernatant of stimulated primary cells from DPF pigs; c) viral load in donor's blood plasma; d) PERV proviral copy number in DPF pig genome; e) PERV class C prevalence in the herd and its recombination potential.

Shortage of human donor organs for transplantation has prompted evaluation of animals as an alternative donor source. Pigs are the most acceptable candidate animals but issues of xenozoonozes remain. Despite careful monitoring of high-health-status (HHS) pigs, there is still a risk that their tissues may carry infectious agents. Furthermore, pathogens which are significant in xenotransplantation are not necessarily those of veterinary importance. The detection of these potentially transmissible infectious agents may require the development and application of new surveillance technologies. We present data on monitoring for five potentially xenotic viruses in New Zealand pig herds, namely pig cytomegalovirus (PCMV), pig lymphotropic herpesvirus (PLHV), encephalomyocarditis virus (EMCV), pigcircovirus (PCV), and hepatitis E virus (HEV). These five viruses are either potentially oncogenic, establish persistent infection, or are known to be zoonotic. This study has expanded significantly the information on porcine viruses in New Zealand. Using this information, it is now possible to complete protocols for monitoring pig herds and tissues prior to their use in xenotransplantation. The study resulted in selection of a possible source herd for swine-to-human islet transplantation.

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