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Biomedical subjects

P Aebischer

Publications and source records attributed to P Aebischer.

156 records · Page 9Linked to original sources
PubMedDate not supplied

Rescue of motoneurons from axotomy-induced cell death by polymer encapsulated cells genetically engineered to release CNTF.

The neurodegenerative disease amyotrophic lateral sclerosis (ALS) results from the progressive loss of motoneurons, leading to death in a few years. Ciliary neurotrophic factor (CNTF), which decreases naturally occurring and axotomy-induced cell death, may result in slowing of motoneuron loss and has been evaluated as a treatment for ALS. Effective administration of this protein to motoneurons may be hampered by the exceedingly short half-life of CNTF, and the inability to deliver effective concentration into the central nervous system after systemic administration in vivo. The constitutive release of CNTF from genetically engineered cells may represent a solution to this delivery problem. In this work, baby hamster kidney (BHK) cells stably tranfected with a chimeric plasmid construct containing the gene for human or mouse CNTF were encapsulated in polymer fibers, which prevents immune rejection and allow long-term survival of the transplanted cells. In vitro bioassays show that the encapsulated transfected cells release bioactive CNTF. In vivo, systemic delivery of human and mouse CNTF from encapsulated cells was observed to rescue 26 and 27% more facial motoneurons, respectively, as compared to capsules containing parent BHK cells 1 wk postaxotomy in neonatal rats. With local application of CNTF on the nerve stump and by systemic delivery through repeated subcutaneous injections, 15 and 13% more rescue effects were observed. These data illustrate the potential of using encapsulated genetically engineered cells to continuously release CNTF to slow down motoneuron degeneration following axotomy and suggest that encapsulated cell delivery of neurotrophic factors may provide a general method for effective administration of therapeutic proteins for the treatment of neurodegenerative diseases.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

Polymer encapsulated neurotransmitter secreting cells. Potential treatment for Parkinson's disease.

Parkinson's disease, a neurologic disorder characterized by a dopamine deficit within the striatum, may be improved by transplantation of polymer encapsulated neurosecretory cells. Surrounding cells with a selectively permeable barrier offers several advantages, including preventing immune rejection and tumor formation while allowing functional efficacy. Bovine adrenal medullary chromaffin cells, or PC12 cells, a rat-derived pheochromocytoma cell line, were encapsulated within polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules. Histologic and biochemical analyses revealed that both types of cells survived and that neurotransmitter release from capsules was sustained for several months in vitro, irrespective of the encapsulation method employed. Both of the encapsulation systems protected the enclosed cells from an immunologic challenge in vitro, and prevented immune rejection when cell containing capsules were implanted in an immunologically incompatible host. Chromaffin or PC12 cell containing capsules implanted into the dopamine (DA) depleted striatum of rats reduced the lesion associated functional deficit. These results suggest that encapsulated neurosecretory cell implants may be useful in treating various central nervous system (CNS) deficits, particularly in cases involving a specific neurochemical lesion.

Adrenal Medulla↗
PubMedDate not supplied

Cellular control of membrane permeability. Implications for a bioartificial renal tubule.

A hemofiltrate processor, which consists of a cultured monolayer of renal epithelial cells on a permeable membrane, displayed transport functions that mimicked the renal tubule. Two cell lines, LLC-PK1 (a proximal tubule-like cell) and MDCK (a distal tubule-like cell), were cultured on microporous cellulose nitrate membranes and studied in a diffusion chamber. Dual-label tracer experiments revealed that inulin, glucose, and para-aminohippurate (PAH) moved across unseeded membranes with similar rates in either direction. Solute concentrations in both compartments reached equilibrium in less than 12 hours. MDCK cell-covered membranes were impermeable to all three solutes, as expected from a distal tubule-like cell. LLC-PK1 cell-covered membranes were impermeable to inulin and PAH, but demonstrated a net apical to basal glucose flux of 150 to 350 ng/cm2/min, depending on the conditions. This led within 72 hours to a zero glucose concentration in the compartment on the apical side of the cells, versus 4.6 mg/ml on the basal side. This glucose transport function was inhibited by 0.5 mmol/L phlorizin. Highest glucose flux was obtained using extracellular matrix as the cell attachment substrate on the membrane, suggesting the highest degree of cell differentiation. Based on estimates of the surface area of the normal kidney, the glucose reabsorption capacity of the LLC-PK1 cell line was about 20% that of the normal tubule. The absence of PAH secretion may have been due to the heterogeneity of cells derived from the proximal tubule. Different cell types, culture conditions, and attachment substrates may enhance the transport capacity of the bioartificial renal tubule.

Animals↗
PubMedDate not supplied

Encapsulated thymic epithelial cells as a potential treatment for immunodeficiencies.

The epithelial cells of the thymus produce hormones that have been implicated in the maturation of T lymphocytes. Thymic epithelial cells can be encapsulated in a permselective polymer membrane that allows the passage of thymic hormones, but prevents the entry of antibodies, complement, cells, and viruses. A pure culture of thymic epithelial cells, identified as such by transmission electron microscopy and keratin staining, was obtained by low temperature organ culture of fetal mouse thymus. These cells remained intact and produced physiologic amounts of the thymic hormone thymosin alpha-1 after encapsulation in a permselective polymer membrane and in vitro culture for 5 days. An encapsulated implant of thymic epithelial cells may therefore promote reconstitution of an immune system in immunodeficiency diseases without allowing the rejection or destruction of the thymic tissue.

Animals↗
PubMedDate not supplied

The bioartificial kidney: progress towards an ultrafiltration device with renal epithelial cells processing.

The combination of an ultrafiltration device with an exchanger whose semipermeable hollow fibres are covered with renal epithelial cells is proposed as a design for a bioartificial kidney. We first demonstrated that continuous ultrafiltration can be maintained for relatively long periods in the absence of anticoagulation. As a second step, we report here the feasibility of attaching and growing two lines of kidney epithelial cells (MDCK and LLC-PK1) on two different semipermeable materials, an acrylic copolymer and a polysulphone. Cells seeded on acrylic copolymer hollow fibres reach confluence within three weeks. Depending on the chemical and/or physical properties of the polymer, the cells show distinct differentiated morphology, which may influence their ability to perform specialized tasks.

Bioprosthesis↗