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Results for “Bioartificial Organs”

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PubMedDate not supplied

A new tracheal bioartificial organ: evaluation of a tracheal allograft with minimal antigenicity after treatment by detergent.

The aim of this study was to reduce the antigenicity of tracheal allografts by detergent treatment. We attempted to apply these grafts to tracheal immunosuppressant-free allotransplantation. Fresh tracheal grafts were harvested from donor beagle dogs and treated with a detergent at 4 degrees C for 48 hours. By using treated grafts, we have performed tracheal immunosuppressant-free transplantation in six dogs at an intrathoracic five-ring defect. Implanted grafts were covered with an omental pedicle. In five of the six grafts, complete removal of the epithelium and mixed glands was recognized with both light microscopy and scanning electron microscopy. The appearance of the cartilage cells in the grafts was similar to those in fresh trachea. Five dogs that received detergent treated grafts survived uneventfully. The grafts had been incorporated by the host trachea without stenosis. On the one tracheal graft in which removal of the epithelium was incomplete (noted after implantation), moderate stenosis occurred 1 month after placement. These results suggest that removal of the tracheal epithelium and mixed glands can remarkably reduce tracheal antigenicity. A tracheal graft that has its epithelium and mixed glands removed can be used in tracheal immunosuppressant-free allotransplantation.

Animals↗
PubMedDate not supplied

New type of tracheal bioartificial organ treated with detergent: maintaining cartilage viability is necessary for successful immunosuppressant free allotransplantation.

The present investigation examined the key factors in the preparation of low-antigenic tracheal allografts by detergent treatment in dogs. In group 1 (n = 5), the grafts were treated by detergent at room temperature for 48 h and rinsed with running water until use. In group 2 (n = 4), detergent treatment was performed at 4 degrees C for 48 h, but the rinsing step was omitted. In group 3 (n = 6), the grafts were treated at 4 degrees C for 48 h, rinsed thoroughly with physiologic saline, and stored at 4 degrees C. The grafts were then used for tracheal replacement without immunosuppressant in dogs. The epithelium and mixed glands had been removed completely from the grafts in groups 1 and 2, and in five of the six grafts of group 3. In groups 1 and 2, cartilage viability appeared to have been lost and all animals died of airway stenosis within 38 days. In group 3, the chondrocytes were viable and all animals survived uneventfully. These results suggest that maintaining cartilage viability in a tracheal graft is necessary for successful immunosuppressant-free allotransplantation and, consequently, to maintain an open airway. The treatment temperature and sufficient rinsing are key factors for maintaining cartilage viability of grafts.

Airway Obstruction↗
PubMed1997

Artificial cells and bioencapsulation in bioartificial organs.

The most common use of artificial cells is for bioencapsulation of biologically active materials. Many combination of materials can be bioencapsulated. The permeability, composition and configurations of artificial cell membrane can be varied using different types of synthetic or biological materials. These possible variations in contents and membranes allow for large variations in the properties and functions of artificial cells.

Animals↗
PubMed2004

Fractal analysis of the vascular tree in the human retina.

The retinal circulation of the normal human retinal vasculature is statistically self-similar and fractal. Studies from several groups present strong evidence that the fractal dimension of the blood vessels in the normal human retina is approximately 1.7. This is the same fractal dimension that is found for a diffusion-limited growth process, and it may have implications for the embryological development of the retinal vascular system. The methods of determining the fractal dimension for branching trees are reviewed together with proposed models for the optimal formation (Murray Principle) of the branching vascular tree in the human retina and the branching pattern of the human bronchial tree. The limitations of fractal analysis of branching biological structures are evaluated. Understanding the design principles of branching vascular systems and the human bronchial tree may find applications in tissue and organ engineering, i.e., bioartificial organs for both liver and kidney.

Animals↗
PubMedDate not supplied

[The technical requirements for artificial life support systems].

The author advances a summarized concept of the bioartificial organism consisting of an operator, equipment and biological medium. Formulates the principle of man-made life support, reviews a model of the bioartificial organism and a classification of processors that ensure the control of the physiological status of the biological medium.

Artificial Organs↗
PubMed2005

Engineering of a vascularized scaffold for artificial tissue and organ generation.

Tissue engineering is an emerging field in regenerative medicine to overcome the problem of end-stage organ failure. However, complex tissues and organs need a vascular supply to guaranty graft survival and render bioartificial organ function. Here we developed methods to decellularize porcine small bowl segments and repopulate the remaining venous and arterial tubular structures within these matrices with allogeneic porcine endothelial progenitor cells. Cellular adherence and vitality was characterized by quantitative 2-[18F]-fluoro-2'-desoxy-glucose (FDG) positron emission tomography (PET) and subsequent immunohistological work up. The generated matrices showed insulin-dependent FDG uptake predominantly in the region of the former vascular structures. Stain for vitality and the specific endothelial markers CD31, VE-Cadherin and Flk-1 matched this functional finding. Providing evidence for vitality up to 3 weeks post reconstitution and typical endothelial differentiation, these results indicate that our generated matrix allows the generation of complex bioartificial tissues and organs for experimental and future clinical application.

Animals↗
PubMed2001

Purification of polymeric biomaterials.

Employing a combined filtration and precipitation method, the endotoxin concentration in sodium alginate (SA) and sodium cellulose sulfate (SCS) was reduced to a value of 200 EU/g polymer. This is one tenth of the regulatory threshold calculated, for example, for an appropriate bioartificial pancreas that consists of approximately 420,000 encapsulated islets of Langerhans. The low endotoxin (ET) levels were maintained below this threshold during a six-month storage period. The purification procedure of the polymers did not negatively influence the final microcapsule properties. The mechanical stability of microcapsules from purified material is even slightly higher than that of microcapsules from the original polymers. A second approach to avoid endotoxin release from the device is its direct complexation during the bead or capsule formation process. The durability of endotoxin binding in binary, ternary, and quaternary complexes could be demonstrated for storage in culture medium and saline. Very low total endotoxin release from the complexes was detected after three months in culture medium and five months in saline. This complexation is primarily based on electrostatic interactions with the participating cationic components and provides additional security for the final bioartificial organ or delivery device.

Alginates↗
PubMed2005

Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes.

BACKGROUND/AIMS: Liver failure is a life threatening condition currently treated by palliative measures and, when applicable, organ transplantation. The use of a bioartificial organ capable of fulfilling the main functions of the liver would represent an attractive alternative. However, the shortage of suitable donor cells, and their limited growth ability have impeded the development of this strategy. We investigated whether lentiviral vectors allow for conditional immortalization of human hepatocytes and whether these immortalized hepatocytes could reverse lethal acute liver failure. METHODS: We exposed primary human hepatocytes to Cre-excisable lentiviral vectors coding for SV40T Antigen, telomerase, and/or Bmi-1 and tested the functionality of the resulting cell lines. Therapeutic potential of immortalized hepatocytes were tested in a murine model of acetaminophen-induced hepatic injury. RESULTS: The immortalized hepatocytes grew continuously yet were non-tumorigenic, stopped proliferating when exposed to Cre recombinase, and conserved defining properties of primary hepatocytes, including the ability to secrete liver-specific proteins and to detoxify drugs. The implantation of encapsulated immortalized human hepatocytes rescued mice from lethal doses of acetaminophen. CONCLUSIONS: Lentiviral vectors represent tools of choice for immortalization of non-dividing primary cells, and lentivirally immortalized human hepatocytes are promising reagents for cell-based therapy of acute liver failure.

Acetaminophen↗
PubMed1999

Effectiveness of polyamidoamine dendrimers modified with tripeptide growth factor, glycyl-L-histidyl-L-lysine, for enhancement of function of hepatoma cells.

Cationic polyamidoamine dendrimers are known to be highly branched cascade polymers. Tripeptide growth factor, glycyl-L-histidyl-L-lysine (GHK), was employed as a ligand for activation or attachment of cells from a rat hepatoma cell line, H4-H-E-C3, and immobilized at the terminus of the dendrimer (GHK-dendrimer) to develop a suitable surface for use as a culture substratum in the bioartificial liver support system (BAL). The growth of cells was inhibited by increasing the number of generations of GHK-dendrimers. On the other hand, urea synthesis and lidocaine clearance of the cells adhered on fifth generation GHK-dendrimers were enhanced much more than on first generation GHK-dendrimers. GHK was shown to act as a growth inhibitor and an activator of hepatoma cells. These properties of GHK are advantageous for the utilization of hepatoma cells in BAL. Ligand-modified dendrimers are very promising for the creation of a high-performance substratum for cell culture and high performance bioartificial organs, as well as for high-performance bioartificial liver systems. GHK may have the potential to be a highly useful ligand.

Journal Article↗
PubMed2000

Impact of developmental biology on medicine.

How a single zygote develops into a complex organism is the greatest mystery in biomedical science. The discipline of studying this developmental process is called "developmental biology". With advances in genetics, molecular biology, and genomics and judicious use of various model organisms, modern developmental biologists are gradually unveiling the mystery of the developmental process. During this process, embryonic cells proliferate and differentiate to form various tissues and organs. Eventually, a fully functioning organism results. The embryo possesses the mysterious power to give rise to all kinds of new cells and tissues. If we can harness the power of embryogenesis, the lost function of a diseased organ might be restored. To demonstrate the potential impact of developmental research on future medical care, we cite major progress in several areas such as 1) the search for human disease genes and the study of gene function using model organisms; 2) the power of stem cells; and 3) bioartificial organs. Medical researchers in the 21st century should have an ample knowledge of developmental biology and an ability to use various model organisms to study gene function. Through this, new treatments using the power of embryogenesis may evolve.

Animals↗
PubMed1981

The bio-artificial organ: review and progress report.

A definition and a review is given for the bioartificial organ. In addition new developments are reported with the successful lyophilization of enzyme filled RCG with cryoprotective polyethylene glycol (PEG). The successful use of an enzyme reactor consisting of crosslinked fibrin with asparaginase covalently attached is reported in sheep. The small organ (0.4 m2) removes 70% of the animal's asparagine in 6 hours. No enzyme leakage down to 10(-5) units per ml. plasma could be found. The highly preserved substrate affinity of insolubilized asparaginase as well as its high activity and stability when bound to fibrin are additional outstanding features of this system.

Animals↗