Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bioartificial Organs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed2003

Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types.

Multicellular tumor spheroids (MCTS) are used as organotypic models of normal and solid tumor tissue. Traditional techniques for generating MCTS, such as growth on nonadherent surfaces, in suspension, or on scaffolds, have a number of drawbacks, including the need for manual selection to achieve a homogeneous population and the use of nonphysiological matrix compounds. In this study we describe a mild method for the generation of MCTS, in which individual spheroids form in hanging drops suspended from a microtiter plate. The method has been successfully applied to a broad range of cell lines and shows nearly 100% efficiency (i.e., one spheroid per drop). Using the hepatoma cell line, HepG2, the hanging drop method generated well-rounded MCTS with a narrow size distribution (coefficient of variation [CV] 10% to 15%, compared with 40% to 60% for growth on nonadherent surfaces). Structural analysis of HepG2 and a mammary gland adenocarcinoma cell line, MCF-7, composed spheroids, revealed highly organized, three-dimensional, tissue-like structures with an extensive extracellular matrix. The hanging drop method represents an attractive alternative for MCTS production, because it is mild, can be applied to a wide variety of cell lines, and can produce spheroids of a homogeneous size without the need for sieving or manual selection. The method has applications for basic studies of physiology and metabolism, tumor biology, toxicology, cellular organization, and the development of bioartificial tissue.

Breast Neoplasms↗
PubMed2004

Large animal models of fulminant hepatic failure in artificial and bioartificial liver support research.

Among the large range of organs involved in the field of tissue engineering (skin, blood vessels, cartilage, etc.) the liver has been given broad attention in the last decade. Liver support systems encompassing artificial and bioartificial systems are applied to treat patients with fulminant hepatic failure (FHF) as a bridge to orthotopic liver transplantation or to liver regeneration. To test safety, technical applicability and therapeutic effect of liver support systems, reliable animal models are needed. Due to the complexity of FHF many diverse attempts have been made to develop an adequate animal model to study liver failure, liver regeneration and liver support systems. In this paper an overview is given of the different models and their advantages and disadvantages are discussed. Suggestions are made for the most suitable large animal model to test liver support systems.

Acetaminophen↗
PubMed2006

Present status and perspective of the development of a bioartificial kidney for chronic renal failure patients.

A bioartificial tubule device was applied for the treatment of 10 acute renal failure and multiple organ failure patients by Humes et al. A bioartificial kidney for chronic renal failure patients, however, has never been applied. In order to develop a bioartificial kidney for preventing and treating long-term complications of maintenance dialysis patients, we have to overcome difficulties such as antithrombogenic issue of hemofilters and development of long functioning tubule devices in the context of economical and easy treatment. Continuous hemofilters should modify with an antithrombogenic material on the inner surfaces of membranes to get more hemocompatible characteristics. We are developing an antithrombogenic continuous hemofilter coating with methacryloyloxyethyl phosphorylcholine polymer which will mimic phospholipid layers of human cell membrane on the inner surface of a hemofilter. The transportability of H2O, Na+, and glucose of bioartificial tubule devices using polysulfone hollow fiber modules and porcine proximal tubular epithelial cells LLC-PK1 were evaluated using two kinds of circuits of different medium inside and outside of the cell-attached hollow fiber membrane. Transport of H2O, Na+, and glucose were significantly increased when 2.5 g/dL of albumin was added, and plateaued on the eight day and then decreased thereafter until the 13th day. Transfection of a specific gene into human tubular epithelial cells might be required to keep contact inhibition in order to maintain a confluent monolayer for longer duration.

Animals↗
PubMed2004

Bioartificial tracheal grafts: can tissue engineering keep its promise?

A huge variety of graft materials and transplantation approaches have been applied for decades in order to generate a clinically applicable tracheal substitute; so far, without success. Today, tissue engineering, the creation of man-made functional biological organs or tissue replacements from biodegradable carrier structures and autologous cells, may represent an alternative to the shortage of suitable grafts for reconstructive airway surgery. Partial success has been obtained by numerous groups following different concepts and strategies. In this article, tissue engineering approaches towards the bioartificial airway prosthesis are discussed, focusing primarily on recent developments in the field.

Animals↗
PubMed1998

Attenuation of skeletal muscle wasting with recombinant human growth hormone secreted from a tissue-engineered bioartificial muscle.

Skeletal muscle wasting is a significant problem in elderly and debilitated patients. Growth hormone (GH) is an anabolic growth factor for skeletal muscle but is difficult to deliver in a therapeutic manner by injection owing to its in vivo instability. A novel method is presented for the sustained secretion of recombinant human GH (rhGH) from genetically modified skeletal muscle implants, which reduces host muscle wasting. Proliferating murine C2C12 skeletal myoblasts stably transduced with the rhGH gene were tissue engineered in vitro into bioartificial muscles (C2-BAMs) containing organized postmitotic myofibers secreting 3-5 microg of rhGH/day in vitro. When implanted subcutaneously into syngeneic mice, C2-BAMs delivered a sustained physiologic dose of 2.5 to 11.3 ng of rhGH per milliliter of serum. rhGH synthesized and secreted by the myofibers was in the 22-kDa monomeric form and was biologically active, based on downregulation of a GH-sensitive protein synthesized in the liver. Skeletal muscle disuse atrophy was induced in mice by hindlimb unloading, causing the fast plantaris and slow soleus muscles to atrophy by 21 to 35% ( < 0.02). This atrophy was significantly attenuated 41 to 55% (p < 0.02) in animals that received C2-BAM implants, but not in animals receiving daily injections of purified rhGH (1 mg/kg/day). These data support the concept that delivery of rhGH from BAMs may be efficacious in treating muscle-wasting disorders.

Animals↗
PubMedDate not supplied

Cell-based therapy for liver diseases.

Although liver transplantation has become standard therapy in the treatment of patients with liver failure, several problems should be considered in the management of these patients. Other approaches have been proposed, in particular cellular-based procedures. Isolated hepatocytes may be used instead of whole organ transplantation or integrated within the bioartificial devices, in order to replace the missing synthetic and metabolic liver functions. Moreover patient's own hepatocytes may be ex vivo genetically modified to provide the function of a mutant gene. However, new cell sources alternative to adult hepatocytes are actually under investigation, on the basis of recent advances in the field of liver repopulation. Xenogenic primary cells, human hepatoma cells, immortalized hepatocytes and stem cells have been testing in several experiments, even if up to now none of them represent a "gold-standard" for cell-based treatment of liver diseases. In the next future, it is possible that different clinical situations will require different therapeutic approaches, that will be finally defined from the concomitant advances in the development of artificial devices and liver cell biology.

Cell Transplantation↗
PubMed2004

Renal cell therapy in the treatment of patients with acute and chronic renal failure.

Hemodialysis and hemofiltration have been important technologies in saving the lives of patients with acute (ARF) and chronic renal failure by clearing small solutes from plasma and thereby preventing death from acidemia, hyperkalemia, volume overload, and uremia. These therapeutic approaches, however, are still suboptimal, as patients with ARF have mortality rates exceeding 50%, and patients with end-stage renal disease (ESRD) have, on average, a life expectancy of 4-5 years. The preeminent cause of death in patients with ARF is the development of sepsis or the systemic inflammatory response syndrome with resulting systemic vasodilation, hypotension, ischemic injury to solid organs, multi-organ failure, and death. This vasodilation is due to persistent and excessive pro-inflammation. Similarly, the reduced survival times of patients with ESRD on chronic dialysis have been associated with a persistent and chronic systemic pro-inflammatory state. We have hypothesized that the loss of renal tubule cell mass acutely in acute tubule necrosis and chronically in ESRD results in an immunologically dysregulated state leading to excessive pro-inflammation. The replacement of renal tubule cell function may thus change the current dismal prognosis of patients with these disorders. In this regard, this report presents the first patient ever treated with a bioartificial kidney consisting of a synthetic hemofilter in series with a renal tubule assist device (RAD) containing approximately 10(9) human renal tubule cells. This treatment in a critically ill patient with multi-organ failure and ARF in the intensive care unit was associated temporally with improved cardiovascular parameters and enhanced native kidney function. Multiple systemic plasma cytokine levels and gene expression profiles of peripheral white blood cells were also temporally changed with cell therapy. Clinical trials in patients suffering from either ARF or ESRD are currently ongoing to evaluate the influence of the RAD on the inflammatory response in these groups of patients.

Acute Kidney Injury↗
PubMed2002

A bioartificial liver--state of the art.

End-stage liver disease is treated by liver transplantation, but donor organ shortages remain a serious problem. This has prompted the design of bioartificial liver devices to "bridge" patients until they either recover or receive a liver transplant. In these devices, patient plasma is circulated extracorporeally through a bioreactor that houses liver cells (hepatocytes) sandwiched between artificial plates or capillaries.

Animals↗
PubMed2003

Tissue engineering in otorhinolaryngology.

Tissue engineering is a field of research with interdisciplinary cooperation between clinicians, cell biologists, and materials research scientists. Many medical specialties apply tissue engineering techniques for the development of artificial replacement tissue. Stages of development extend from basic research and preclinical studies to clinical application. Despite numerous established tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue engineering techniques opens up new ways for cell and tissue repair in this medical field. Autologous cartilage still remains the gold standard in plastic reconstructive surgery of the nose and external ear. The limited amount of patient cartilage obtainable for reconstructive head and neck surgery have rendered cartilage one of the most important targets for tissue engineering in head and neck surgery. Although successful in vitro generation of bioartificial cartilage is possible today, these transplants are affected by resorption after implantation into the patient. Replacement of bone in the facial or cranial region may be necessary after tumor resections, traumas, inflammations or in cases of malformations. Tissue engineering of bone could combine the advantages of autologous bone grafts with a minimal requirement for second interventions. Three different approaches are currently available for treating bone defects with the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based therapy, and (3) cell-based therapy. All three treatment strategies can be used either alone or in combination for reconstruction or regeneration of bone. The use of respiratory epithelium generated in vitro is mainly indicated in reconstructive surgery of the trachea and larynx. Bioartificial respiratory epithelium could be used for functionalizing tracheal prostheses as well as direct epithelial coverage for scar prophylaxis after laser surgery of shorter stenoses. Before clinical application animal experiments have to prove feasability and safety of the different experimental protocols. All diseases accompanied by permanently reduced salivation are possible treatment targets for tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head and neck tumors is of particular importance here due to the high number of affected patients. The number of new diseases is estimated to be over 500,000 cases worldwide. Causal treatment options for radiation-induced salivary gland damage are not yet available; thus, various study groups are currently investigating whether cell therapy concepts can be developed with tissue engineering methods. Tissue engineering opens up new ways to generate vital and functional transplants. Various basic problems have still to be solved before clinically applying in vitro fabricated tissue. Only a fraction of all somatic organ-specific cell types can be grown in sufficient amounts in vitro. The inadequate in vitro oxygen and nutrition supply is another limiting factor for the fabrication of complex tissues or organ systems. Tissue survival is doubtful after implantation, if its supply is not ensured by a capillary network.

Animals↗
PubMed2000

From the intestinal neobladder to the bioartificial bladder: remarks on some biological implications.

In an attempt to avoid the complications associated with use of bowel for bladder augmentation or replacement (systemic metabolic imbalances, malignancy, etc.), various solutions have been proposed for an artificial orthotopic neobladder: total alloplastic prosthetic bladder in nonbiological material (silicon rubber, polyurethane, etc.); tissue-engineered bladder by the patient's own urothelial--and smooth muscle--cells obtained by biopsy of a urinary segment with less neoplastic potential and cultured in vitro, then seeded onto biodegradable bladder-shaped scaffold, autografted in the original host; bladder augmentation or replacement using acellular matrix derived from small-intestinal submucosa or from bladder or ureter as a scaffold structure for the subsequent regrowth of functional organ. Tissue-engineering technology with autologous native cells is being undertaken for every type of organ within the urinary tract. At the present moment, other roads are less practicable, e.g. to obtain "spare bladders" from human therapeutic cloning or from transgenic-humanized animals.

Bioartificial Organs↗
PubMed1997

Microcapsules as bio-organs for somatic gene therapy.

Current human gene therapy relies on genetic modification of the patient's own cells. An alternate non-autologous approach is to use universal cell lines engineered to secrete therapeutic products. Protection with immuno-isolation devices would allow the same recombinant cell line to be used for different patients, thus potentially lowering the cost of treatment. The feasibility of this idea has now been demonstrated in vitro and in vivo. Recombinant gene products with potential therapeutic applications (human growth hormone, factor IX, lysosomal enzymes, adenosine deaminase) have been expressed from genetically modified cells after encapsulation with alginate-poly-L-lysine-alginate or hydroxyethyl methacrylate-methyl methacrylate. We have also demonstrated the feasibility of this idea in vivo. After intraperitoneal implantation, genetically modified mouse Ltk- fibroblasts or C2C12 myoblasts encapsulated in alginate-poly-L-lysine-alginate could deliver recombinant gene products (human growth hormone, human factor IX) to the systemic circulation of mice. The clinical efficacy of this novel approach to gene therapy has now been shown in murine models of human diseases. In the Snell dwarf mice deficient in growth hormone production, implantation of encapsulated mouse myoblasts engineered to secrete mouse growth hormone resulted in increases in body weight, length and organ sizes, some to > 25% above those of the controls. In the Gus/Gus mice suffering from the lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase, implantation of encapsulated mouse fibroblasts engineered to secrete mouse beta-glucuronidase resulted in delivery of normal levels of the enzyme in the plasma and significant correction of the organ histopathology. Hence, delivery of recombinant gene products through bioartificial devices appears to be a promising strategy for the treatment of genetic diseases.

Alginates↗
PubMed1997

Treatment of severe liver failure with a bioartificial liver.

Orthotopic liver transplantation (OLT) is the definitive therapy for severe liver failure. However, many patients die before an organ becomes available, mostly from cerebral edema. To provide temporary liver support, we developed a bioartificial liver (BAL) based on porcine hepatocytes and a charcoal column. Fifty-four consecutive BAL treatments were carried out in three groups of patients: Group I (n = 15) patients presented with FHF were listed for emergent OLT, Group II (n = 3) patients with primary non-function (PNF) of their liver grafts required urgent re-transplantation and Group III (n = 10) patients with acute exacerbation of chronic liver disease were not candidates for OLT. Patients were managed in a critical care unit receiving maximal standard support. Each BAL treatment was conducted for 6 hours. In Group I, all patients showed significant neurologic improvement, intracranial pressure (ICP) decreased and cerebral perfusion pressure (CPP) increased; other significant improvements, included lowered plasma ammonia and liver enzymes and increased glucose. One patient recovered spontaneously without OLT, all other patients were "bridged" to OLT, and recovered. Group II: PNF patients showed similar benefits. Group III: Chronic liver patients demonstrated transient beneficial effects after BAL treatment(s), however, most (n = 8) eventually succumbed to sepsis and multiple organ failure as they were not candidates for OLT; two patients, recovered, later were successfully transplanted and survived. Our clinical experience demonstrates that the BAL can serve as a bridge to OLT in patients with acute liver failure.

Adult↗
PubMed2006

Present status and perspectives of bioartificial kidneys.

Currently, hemodialysis is not adequate as a renal replacement therapy because it provides intermittent treatment and does not provide the metabolic function of renal tubules. The next generation of artificial kidney should replace intermittent hemodialysis with continuous hemofiltration and provide the full metabolic function of renal tubules. The current decade has witnessed the development of bioartificial kidneys using artificial membranes and renal tubular epithelial cells. Active transport and metabolic functions were confirmed in the confluent monolayers of tubular cells on artificial membranes. Bioartificial kidneys have succeeded in improving the prognosis of patients with multiple organ dysfunction, presumably by lowering plasma cytokine levels in patients. For successful treatment of chronic renal failure using bioartificial kidneys, it is necessary to overcome some technical hurdles such as improving the antithrombogenic properties of the surface of artificial membranes and prolonging the function of renal tubule cells on an artificial membrane. Transfection of functional protein genes into renal tubule cells enables bioartificial tubule devices to increase their transport capacity and metabolic functions such as digoxin secretion and water transport. The development of wearable roller pumps is also essential for the clinical application of a continuous treatment system.

Biomedical Research↗
PubMed1996

Porcine hepatocytes for biohybrid artificial liver devices: a comparison of hypothermic storage techniques.

Two hypothermic preservation techniques were investigated to assess their possible role in on-demand cell supply for bioartificial liver support devices. Porcine hepatocytes from slaughterhouse organs were isolated and either cold stored in a modified University of Wisconsin solution for up to 72 h or directly cultured in a sandwich configuration, frozen at Day 3 of culture, and stored for up to 30 days with subsequent long-term culture (14 days) in both groups. Cold storage for 72 h resulted in a decreased viability of cells (58.7 +/- 7.9%) with well preserved ultrastructures in the remainder of cells. In subsequent culture, albumin secretion was slightly increased, and cytochrome P450 IA1 dependent 7-ethoxy-coumarine deethylation activity was reduced to about 40% of control values. After cryopreservation, hepatocyte cultures revealed no severe damage to ultrastructures of cells, and functional parameters (albumin, 7-ethoxycoumarine deethylation) were comparable with controls after an initial drop in activity directly after thawing. Length of storage time did not influence results. Both hypothermic preservation protocols might eventually play an important role for bioartificial liver processing and on-demand cell supply, dependent on the individual reactor design.

Albumins↗