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      Artificial Cell Biotechnology for Medical Applications

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          Artificial cells are prepared in the laboratory for medical and biotechnological applications. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure and the use of encapsulated genetically engineered cells for gene therapy. We recently found that daily orally administered artificial cells containing a genetically engineered microorganism can lower the elevated urea level in uremic rats to normal levels and increase the survival of the animal. Furthermore, this can remove potassium, phosphate, uric acid and other waste metabolites from uremic plasma. Blood substitutes based on modified hemoglobin are already in phase-III clinical trials in patients with as much as 20 units infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trials in hereditary enzyme deficiency diseases and other diseases. Artificial cells are also being investigated for drug delivery and other uses in biotechnology, chemical engineering and medicine.

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          A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase.

          Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a genetic disease. However, compliance with dietary treatment is difficult and when it is for life, as now recommended by an internationally used set of guidelines, is probably unrealistic. Herein we describe experiments on a mouse model using another modality for treatment of PKU compatible with better compliance using ancillary phenylalanine ammonia lyase (PAL, EC to degrade phenylalanine, the harmful nutrient in PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase (EC, which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N'-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)-both pharmacologic (with a clear dose-response effect vs. HPA after PAL injection) and physiologic (protected enteral PAL is significantly effective vs. HPA). These findings open another way to facilitate treatment of this classic genetic disease.
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            The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery

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              Transport characterization of membranes for immunoisolation

              This study relates to the diffusive transport characterization of hollow fibre membranes used in implantable bio-hybrid organs and other immunoisolatory devices. Techniques were developed to accurately determine the mass transfer coefficients for diffusing species in the 10(2)-10(5) MW range, validated and then used to study one membrane type known to effectively immunoisolate both allografts and xenografts in vivo. Low-molecular-weight diffusing markers included glucose, vitamin B12 and cytochrome C; higher-molecular-weight molecules were bovine serum albumin, immunoglobulin G, apoferritin and a range of fluorescein-tagged dextrans. Overall and fractional mass transfer coefficients through the hollow fibres were determined using a resistance-in-series model for transport. A flowing dialysis-type apparatus was used for the small-molecular-weight diffusants, whereas a static diffusion chamber was used for large-molecular-weight markers. For diffusion measurements of small-molecular-weight solutes, convective artefacts were minimized and the effect of boundary layers on both sides of the membrane were accounted for in the model. In measuring diffusion coefficients of large-molecular-weight species, boundary layer effects were shown to be negligible. Results showed that for small-molecular-weight species (< 13,000 MW) the diffusion coefficient in the membrane was reduced relative to diffusion in water by two to four times. The diffusion rate of large-molecular-weight species was hindered by several thousand-fold over their rate of diffusion in water.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                03 August 2000
                : 18
                : 2
                : 91-96
                Artificial Cells and Organs Research Centre, Departments of Physiology, Medicine and Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
                14430 Blood Purif 2000;18:91–96
                © 2000 S. Karger AG, Basel

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                References: 58, Pages: 6
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