Functionalizable silica-based MPIO for cellular MRI
23 December 2012 - 14:34
Cellular therapies require methods for non-invasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate strong contrast in
Magnetic Resonance Imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However,
MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles
(sMPIOs) with a functionalizable particle surface.
MRI and ectopic liver cell transplantation – new paper
21 September 2012 - 14:24
Liver cell transplantation is a promising approach for the treatment of metabolic liver disorders. However, a method for noninvasive monitoring during liver cell transplantation is not available clinically. The aim of this study was to investigate the feasibility of fast dynamic MRI monitoring during liver cell infusion to the spleen, which is considered an ectopic implantation site for liver cell transplantation. Porcine liver cells were labeled with micron-sized iron oxide particles and infused to the spleens of pigs (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner. Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast dynamic MRI was performed during cell infusion. MR findings were verified by immunohistological examinations.
Images from static MRI (TR/TE, 2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio after cell infusion compared with pretransplant images. T2-weighted fast dynamic MRI enabled visualization of signal decrease of the spleen during cell infusion. When cells were infused systemically, no signal changes in the spleen were observed. This study shows that fast dynamic MRI can enable noninvasive monitoring during liver cell transplantation to the spleen. This approach could be useful for preclinical studies and for quality control of clinical liver cell transplantation.
SlideObserver in Journal of Biotechnology
12 March 2012 - 11:32
Cell morphology, proliferation and motility, as well as mono- and heterotypic cell-to-cell interactions, are of increasing interest for in vitro experiments. However, tightly controlling culture conditions while simultaneously monitoring the same set of cells is complicated. Moreover, video-microscopy of distinct cells or areas of cells over a prolonged period of time represents a technical challenge. The SlideObserver was designed for cinemicrography of cells in co-and monoculture. The core elements of the system are the SlideReactors, miniaturised hollow fibre-based bioreactors operated in closed perfusion loops. Within the SlideReactors, cells can be cultured under standard and experimental conditions as well as in direct- and indirect co-culture. The independent perfusion loops enable controlled variation of parameters such as medium, pH, and oxygenation. A combined automated microscope stage and camera set-up allows for micrograph acquisition of multiple user-defined regions of interest within the bioreactor units. For proof of concept, primary cells (HUVEC, human hepatocytes) and cell lines (HuH7, THP-1) were cultured under stable and varying culture conditions, as well as in mono- and co-culture. The operational system enabled non-stop imaging and automated control of process parameters as well as elective manipulation of either reactor. As opposed to static culture systems or comparable devices for cinemicrographic analysis, the SildeObserver allows simultaneous morphological monitoring of an entire culture of cells in control and experimental bioreactors.
CARS microscopy of MPIO
10 September 2011 - 09:43
The fruitful cooperation with the FOM Institute AMOLF in Masterdam resulted in the paper "CARS microscopy for the visualization of micrometer-sized iron oxide MRI contrast agents in living cells" (Rago G, Langer CM, Brackman C, Day JP, Domke KF, Raschzok N, Schmidt C, Sauer IM, Enejder A, Mogl MT, Bonn M.) published in Biomed Opt Express. 2011 Sep 1;2(9):2470-83.
Fast dynamic MRI for during liver cell Tx
01 September 2011 - 09:50
Nathanael Raschzok’s paper concerning „Feasibility of fast dynamic MRI for non-invasive monitoring during ectopic liver cell transplantation to the spleen in a porcine model“ was accepted for publication in American Journal of Roentgenology . Authors are N. Raschzok, J. Pinkernelle, N. Billecke, K. Nehls, M. Powerski, I.M. Sauer and U. Teichgraber.
Improved cold storage of human hepatocytes
31 August 2011 - 09:37
Increasing amounts of human hepatocytes are needed for clinical applications and different fields of research, such as cell transplantation, bioartificial liver support and pharmacological testing. This demand calls for adequate storage options for isolated human liver cells. As cryopreservation results in severe cryoinjury, short term storage is currently performed at 2-8º C in preservation solutions developed for the storage of solid organs. However, besides slowing down cell metabolism, cold also induces cell injury, which is, in many cell types, iron-dependent and not counteracted by current storage solutions. In this study, we aimed to characterize storage injury to human hepatocytes and develop a customized solution for cold storage of these cells. Human hepatocytes were isolated from material obtained from partial liver resections, seeded in monolayer cultures and, after a pre-culture period, stored in the cold in classical and new solutions followed by rewarming in cell culture medium.Human hepatocytes displayed cold-induced injury, resulting in > 80% cell death (LDH release) after one week of cold storage in University of Wisconsin solution or cell culture medium and 3 h of rewarming. Cold-induced injury could be significantly reduced by the addition of the iron chelators deferoxamine and LK 614. Experiments with modified solutions based on the new organ preservation solution Custodiol-N showed that ion-rich variants were better than ion-poor variants, chloride-rich solutions better than chloride-poor solutions, potassium as main cation superior to sodium and pH 7.0 superior to pH 7.4. LDH release after two weeks of cold storage in the thus optimized solution was below 20%, greatly improving cold storage of human hepatocytes. The results were confirmed by the assessment of hepatocellular mitochondrial membrane potential and functional parameters (resazurin reduction, glucacon-stimulated glucose liberation) and thus suggest the use of a customized hepatocyte storage solution for the cold storage of these cells.
Profiles of microRNA after rat partial hepatectomy
10 March 2011 - 16:21
Labelling of hepatocytes in suspension culture
01 March 2011 - 19:21
Protocols for labelling of hepatocytes with micron-sized iron oxide particles (MPIO) in adhesion culture enable cell detection using clinical Magnetic Resonance equipment. For clinical applications, large numbers of cells must be labelled in a simple and rapid manner, which requires new labelling protocols. The aim of this study was to investigate the feasibility of preparing MPIO-labelled primary human hepatocytes in a temporary suspension culture. Human hepatocytes were isolated from 16 donors and labelled with MPIO in suspension, using the Rotary Cell Culture System. Particle incorporation was investigated by light and electron microscopy. Cells were compared to adhesion culture-labelled and subsequently enzymatically resuspended cells. During a five-day culture period, hepatocyte-specific parameters of cell damage (aspartate aminotransferase and alanine aminotransferase) and metabolic activity (urea and albumin) were analysed. Suspension cultures showed a higher outcome in cell recovery compared to the conventional labelling method. When incubated with 180 particles/cell for four hours, the mean particle uptake was 28.8 particles/cell at a labelling efficiency of 95.1%. Labelling in suspension had no adverse effects on cell integrity or metabolic activity. In conclusion, labelling in suspension is a practicable method for fast and efficient preparation of large numbers of labelled cells that are suitable for clinical applications.
Monitoring cell transplantation in swine model via MRI
07 January 2011 - 19:22
Liver cell transplantation (LCT) is a promising treatment approach for certain liver diseases, but clinical implementation requires methods for non-invasive follow-up. Labeling with superparamagnetic iron oxide particles can enable the detection of cells with magnetic resonance imaging (MRI). We investigated the feasibility of monitoring transplanted liver cells by MRI in a preclinical swine model and used this approach to evaluate different routes for cell application. Liver cells were isolated from landrace piglets and labeled with micron-sized iron oxide particles (MPIO) in adhesion. Labeled cells (n = 10), native cells (n = 3) or pure particles (n = 4) were transplanted to minipigs via intraportal infusion into the liver, direct injection into the splenic parenchyma, or intra-arterial infusion to the spleen. Recipients were investigated by repeated 3.0 Tesla MRI and computed tomography angiography up to 8 weeks after transplantation. Labeling with MPIO, which are known to have a strong effect on the magnetic field, enabled non-invasive detection of cell aggregates by MRI. Following intraportal application, which is commonly applied for clinical LCT, MRI was able to visualize the microembolization of transplanted cells in the liver that were not detected by conventional imaging modalities. Cells directly injected into the spleen were retained, whereas cell infusions intraarterially into the spleen led to translocation and engraftment of transplanted cells in the liver, with significantly fewer microembolisms compared to intraportal application. These findings demonstrate that MRI can be a valuable tool for non-invasive elucidation of cellular processes of LCT and - if clinically applicable MPIO are available - for monitoring of LCT under clinical conditions. Moreover, the results clarify mechanisms relevant for clinical practice of LCT, suggesting that the intra-arterial route to the spleen deserves further evaluation.
SPAD in children with acute liver failure
01 October 2010 - 22:23
The paper reports on a retrospective data review of uncontrolled clinical data of an university-based pediatric intensive care unit collaborating with a local center for liver transplantation. Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria. Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure. The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 7), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin. In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and requires little training. Whether and to what extent single-pass albumin dialysis can support children with acute liver failure until native liver recovery remain unclear.
Hypothermia-induced cell protection & microglial cells
02 April 2010 - 22:55
Despite the widespread interest in the clinical applications of hypothermia, the cellular mechanisms of hypothermia-induced neuroprotection have not yet been clearly understood. Therefore, the aim of this study was to elucidate the cellular effects of clinically relevant hypothermia and rewarming on the morphological and functional characteristics of microglia. Microglial cells were exposed to a dynamic cooling and rewarming protocol. For stimulation, microglial cells were treated with 1 μg/mL lipopolysaccharide (LPS). We found that hypothermia led to morphological changes from ramified to ameboid cell shapes. At 2 h after hypothermia and rewarming, microglial cells were again ramified with extended branches. Moreover, we found enhanced cell activation after rewarming, accompanied by increased phagocytosis and adenosine triphosphate consumption. Interestingly, hypothermia and rewarming led to a time-dependent significant up-regulation of the anti-inflammatory cytokines interleukin-10 and interleukin-1 receptor antagonist in stimulated microglial cells. This is in line with the reduced proliferation and time-dependent down-regulation of the pro-inflammatory cytokines tumor necrosis factor-alpha and monocyte chemotactic protein-1 in comparison to normothermic control cells after LPS stimulation. Furthermore, degradation of the inhibitor of the nuclear transcription factor-kappaB (IkappaB-alpha) was diminished and delayed under conditions of cooling and rewarming in LPS-stimulated microglial cells. Thus, our results show that hypothermia and rewarming activate microglial cells, increase phagocytosis and shift the balance of cytokine release in stimulated microglial cells towards the anti-inflammatory cytokines. This could be a new cellular mechanism of hypothermia-induced neuroprotection mediated by activated microglial cells.
European Journal of Neuroscience, 2010; 31: 779-787
Modified nanoparticles & multimodal imaging
11 March 2010 - 23:08
Cell transplantation is a major field in regenerative medicine and a promising alternative to whole organ transplantation. However, the process of cell engraftment is not yet fully understood and the hitherto achieved clinical outcome is limited. The aim of our study was to modify an aminosilan-coated nanoparticle for cell labeling and make it applicable for multimodal imaging using MRI, PET and fluorescent imaging. HIV-1 tat, linked FITC, and Gallium-68 were covalently bound to the particle and injected into Wistar rats. Animal-PET imaging was performed followed by MRI at 3.0T. Hepatic accumulation of the particles was proven by radionuclide distribution after 10 minutes in PET as well as in MRI over a 24 hour-period. Histological workup of the liver also revealed content of iron oxide particles in the reticuloendothelial system. Adjacent in vitro studies incubating hepatogenic HuH7 cells with the particles showed a rapid intracellular accumulation, clearly detectable by fluorescence microscopy and MRI. In conclusion our modified nanoparticle is stable under in vitro and in vivo conditions and is applicable for multimodal molecular imaging. Cellular labeling with this particle is possible and might help to get new insights into understanding the process of cell transplantation.
cBAL111
01 November 2009 - 23:10
A clonal cell line that combines both stable hepatic function and proliferation capacity is desirable for in vitro applications that depend on hepatic function, such as pharmacological or toxicological assays and bioartificial liver systems. The article describes the generation and characterization of a clonal human cell line for in vitro hepatocyte applications.Cell clones derived from human fetal liver cells were immortalized by over-expression of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed hepatic functionality similar to the parental cells prior to immortalization, and did not grow in soft agar. Cell line cBAL111 expressed markers of immature hepatocytes, like glutathione S transferase and cytokeratin 19, as well as progenitor cell marker CD146 and was negative for lidocaine elimination. On the other hand, the cBAL111 cells produced urea, albumin and cytokeratin 18 and eliminated galactose. In contrast to hepatic cell lines NKNT-3 and HepG2, all hepatic functions were expressed in cBAL111, although there was considerable variation in their levels compared with primary mature hepatocytes. When transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the liver and partly differentiated into hepatocytes showing expression of human albumin and carbamoylphosphate synthetase without signs of cell fusion. This novel liver cell line has the potential to differentiate into mature hepatocytes to be used for in vitro hepatocyte applications.
Two articles among top 25
10 July 2009 - 23:18
The Editor-in-Chief Paul S. Malchesky of Artificial Organs informed us that the articles "`Blogs` and `Wikis Are Valuable Software Tools for Communication Within Research Groups" and "Isolation of primary human hepatocytes after partial hepatectomy: criteria for identification of the most promising liver specimen" were in the top 25 articles viewed online in 2008 at Blackwell Synergy.
Hypothermia induced endothelial dysfunction
05 April 2009 - 23:23
Hypothermia is used to preserve organs for transplant and it is the oldest method to protect organs during complex pediatric cardiac surgery. Loss of tissue function and tissue edema are common complications in children undergoing cardiac surgery and heart transplantation. The present study was designed to examine the effects of methylprednisolone (MP) and Tacrolimus (TAC) on endothelial cell function and morphology after deep hypothermia and rewarming. Human umbilical vein endothelial cells (HUVECs) were pretreated with MP and/orTAC and incubated either within a specially designed bioreactor or in monolayers. They were then exposed to a dynamic cooling and rewarming protocol. Immunocytochemistry, time lapse video microscopy within the SlideReactor bioreactor system, cell permeability and adherence assays and western blot analysis were performed. Confluent endothelial cells exposed to hypothermia displayed elongated cell shapes with intercellular gap formation, increased endothelial cell-layer permeability and loss in adherence. Upon rewarming, however, endothelial cell integrity was restored. Opening and closing of intercellular gaps was dependent on ERK 1/2 activation and connexin 43 (Cx43) expression. The combined treatment with MP and TAC inhibited these hypothermia-induced changes. These results suggest that MP and TAC inhibit hypothermia induced endothelial gap formation via pERK 1/2 inhibition and connexin 43 stabilization. Application of combined drugs that affect multiple targets may therefore be considered as a possible new therapeutic strategy to prevent endothelial dysfunction after hypothermia and rewarming.
CSAAS and MPIO-labelled cells
04 March 2009 - 23:24
Detection of cells after transplantation is necessary for quality control in regenerative medicine. Labelling with micron-sized iron oxide particles (MPIOs) enables non-invasive detection of single cells by magnetic resonance imaging. However, techniques for evaluation of the particle uptake are challenging. The aim of this study was to investigate continuum source atomic absorption spectrometry (CSAAS) for this purpose. Porcine liver cells were labelled with MPIOs and the iron concentration of the cell samples was investigated by a CSAAS spectrometer equipped with a Perkin-Elmer THGA graphite furnace. The weak iron line at 305.754 nm provides only about 1/600 sensitivity of the iron resonance line at 248.327 nm and was used for CSAAS measurements. Iron concentrations measured from labelled cells ranged from (5.8 ± 0.3) to (25.8 ± 0.9) pg Fe/cell, correlating to an uptake of (8.2 ± 0.5) to (25.7 ± 0.8) particles/cell. The results were verified by standardised morphometric evaluation. CSAAS enabled rapid quantification of particle load from small quantities of cells without extensive preparation steps. Thereby, CSAAS could be used for quality control in a clinical setting of cell transplantation.
Management of Acute Kidney Problems
09 December 2008 - 23:34
It also gives a detailed outline of important measures for their clinical management. This reference is intended as a helpful guide for all clinicians involved in the care of patients at risk of developing acute kidney problems.
The book is written for all clinicians who are involved in the care of patients at risk of developing acute kidney problems; e.g. fellows and residents in nephrology, intensive care, internal medicine, anaesthesiology, surgery, paediatrics, diagnostic and interventional radiology, urology, cardiology and clinical immunology.
Imaging of human hepatocytes via MPIO and MRI
02 April 2008 - 23:40
Tat-peptide modified MPIO
01 April 2008 - 23:49
Isolation of primary human hepatocytes
01 March 2008 - 23:50
MELS CellModule vs. AMC-BAL
01 July 2007 - 00:01
SlideReactor: Proof of concept
08 January 2007 - 22:38
Moreover, the editors have chosen one of the figures showing fluorsecent staining of primary human hepatocytes cultured within the SlideReactor as cover-art!
Certain cell types, especially primary human cells, favor a well-defined culture environment offering continuous supply of nutrients and oxygen and waste product removal. Several bioreactors based on special matrices or hollow fibers have been developed that provide such conditions. However, characterization of matrix re-organization or growth of tissue within these systems is possible only after culture termination. Evaluation of the influence of certain medium additives or culture conditions (e.g., temperature, oxygenation) on cell viability, expansion, and differentiation within these systems remains a challenging task. The SlideReactor, a miniaturized hollow fiber-based bioreactor, was developed to enable the observation of cells during culture. An operation concept offering predefined conditions for various cell types has been designed. For proof of concept, primary human cells (hepatocytes, fibroblasts, keratinocytes) and cell lines (HepG2, HuH7, C3A, WiDr, SkHep1) were cultured and observed. A series of experiments (n = 40) showed the feasibility of the set-up; determination of process parameters and continuous observation is possible. The SlideReactor may serve as a simple and cost-efficient tool for cell characterization and optimization of cell-culture conditions.
Trehalose cryoprotective
03 January 2007 - 22:37
Special issue of Therapeutic Apheresis and Dialysis: Cell-Free Artificial Liver Support
01 May 2006 - 22:32
Therapeutic Apheresis and Dialysis, April 2006 - Vol. 10 Issue 2:
S. Mitzner et al.: Albumin Regeneration in Liver Support—Comparison of Different Methods J. Patzer: Principles of Bound Solute Dialysis J. Vienken et al.: How Can Liver Toxins be Removed? Filtration and Adsorption With the Prometheus System K. Rifai et al.: Review Article: Clinical Experience With Prometheus J. Rozga et al.: A Novel Plasma Filtration Therapy for Hepatic Failure: Preclinical Studies S.R. Ash: Sorbent Suspensions vs. Sorbent Columns for Extracorporeal Detoxification in Hepatic Failure D. Falkenhagen: Fluidized Bed Adsorbent Systems for Extracorporeal Liver Support L.J. Li: Artificial Liver Support System in China: A Review Over the Last 30 Years R.A.F.M. Chamuleau: Bioartificial Liver: Its Pros and Cons W. Bernal et al.: Cell-Free Artificial Liver Support: Design of Appropriate Clinical Studies with a guest editorial by I.M. Sauer and U. Baurmeister: Cell-Free Artificial Liver Support.
Articles in the top 25 / top 10 articles viewed online
05 March 2006 - 22:31
Paul S. Malchesky, Editor-in chief of Artificial Organs, informed us that the articles "In vitro evaluation of the transportability of viable primary human liver cells originating from discarded donor organs in bioreactors" (Artificial Organs 2005, 29: 141-151) and "'Blogs' and 'Wikis' are valuable software tools for communication within research groups" (Artificial Organs 2005, 29: 82-83) were in the top 25 and top 10, respectively, concerning articles viewed online in 2005 at Blackwell Synergy. The latter was N°. 2 of Artifcial Organs in 2005...
Gene transfer into primary human hepatocytes
28 November 2005 - 12:28
Artificial Liver Support
02 November 2005 - 17:24
For more than 25 years clinicians and scientists have been trying to improve the treatment of acute hepatic failure. Several devices were developed and hemodialysis procedures were refined. The treatment of fulminant hepatic failure and end-stage liver cirrhosis by liver transplantation became a standard procedure. However, for the successful management of critical situations before and after liver surgery, artificial liver support is still needed. The results achieved with albumin dialysis (MARS System), the Prometheus System, and dialysis and hemofiltration or plasma exchange as well as modular extracorporeal liver support (MELS) and the Amsterdam bioartificial liver (AMC BAL) are discussed in detail regarding their effects in different clinical situations.
In the second half of the book, the remaining problems and expectations for the future of clinical hepatocyte transplantation and stem cell therapy are elucidated.
Leading experts in the fields of artificial devices, bioartificial devices, hepatocyte transplantation and stem cells present the latest data on these topics. Their experience and their data are summarized in this volume, thus providing an exceptional overview of the problems and future perspectives in the field of artificial liver support.
Artificial Liver Support Series: Falk Symposium, Vol. 145 Henne-Bruns, D.; Buttenschön, K.; Fuchs, M.; Lohse, A. (Eds.) Springer-Verlag 2005 (ISBN: 1-4020-3239-0)
Article in the top 25 most viewed
03 June 2005 - 22:17
S. Malchesky, the Editor-in-Chief of Artificial Organs, informed us that our article 'Blogs' and 'wikis' are valuable software tools for communication within research groups. was among the top 25 most viewed online in 2005 to date at Blackwell Synergy in general !
The European artificial organ scene: present status
02 June 2005 - 08:55
The SlideReactor
23 February 2005 - 21:23
Transportability of bioreactors
30 January 2005 - 03:47
The use of primary human liver cells obtained from discarded donor organs is increasingly favored for cell-based extracorporeal liver support systems. However, as cryopreservation of primary human hepatocytes causes a significant loss of metabolic activity, the transport of bioreactors with viable liver cells is required. The aim of this study was to evaluate the impact of two major potential threats to viable cells during transport: temperature changes and mechanical stress. Methods: In each experiment three hollow fiber-based bioreactors were charged with primary human liver cells originating from the same discarded donor organ and were simultaneously kept under culture conditions for 8 days. In total, 18 bioreactors were evaluated. On the fifth day the bioreactors were exposed to hypothermia (4°C, n = 3), to hyperthermia (42°C, n = 3), or served as normothermic controls (37°C, n = 3). In a second test series bioreactors were exposed to vibration (21 Hz for 20 min, thereafter 7 Hz for 160 min, n = 3), or were operated as control cultures (n = 6). The release of hepatocyte-specific enzymes was determined as an indicator for cell damage. Results: Hypothermic stress resulted in a significant release of transaminases and led to disturbances of the histological integrity, all indicating a high degree of cell damage. When compared with the control cultures, hyperthermia and mechanical stress in terms of vibration had no significant effect on the cells. Conclusion: The transport of hollow fiber bioreactors charged with viable primary human liver cells appears to be feasible in transport monitors for perfusion and temperature control.
"Blogs" and "Wikis"
04 January 2005 - 19:46
Kichchadi sums up some further ideas on using RSS, blogs and wikis in research and education: here and here.
At CiteULike and "Weblogs in Higher Education" further information is available.
M.I.T. Technology Review: Regenerative Medizin
01 November 2004 - 21:42
Article on "MELS" in top 10 most cited AO articles
25 October 2004 - 21:41
The Editor-in-Chief of Artificial Organs informed us that the article "Modular Extracorporeal Liver Support" - published in volume 26, issue 8 of Artificial Organs - was among the top 10 most cited for the year 2003!
Hepatology: SPAD vs. MARS
27 April 2004 - 21:31
The detoxification capacities of single-pass albumin dialysis (SPAD), the molecular adsorbents recirculation system, (MARS) and continuous veno-venous hemodiafiltration (CVVHDF) were compared in vitro. In each experiment 4,100 mL of toxin-loaded human plasma was processed for 6.5 hours. MARS treatment (n = 6) was undertaken in combination with CVVHDF. For SPAD (n = 6) and CVVHDF (n = 6) a high-flux hollow fiber hemodiafilter (identical to the MARS filter) was used. Levels of ammonia, urea, creatinine, bilirubin, and bile acids were determined. Concentrations before and after application of detoxification procedures were expressed as differences and were compared using the Kruskal-Wallis test. Post hoc comparisons for pairs of groups were adjusted according to Bonferroni-Holm. Time, group, and interaction effects were tested using the nonparametric ANOVA model for repeated measurements. SPAD and CVVHDF induced a significantly greater reduction of ammonia levels than MARS. No significant differences were found among SPAD, MARS, and CVVHDF with respect to other water-soluble substances. SPAD induced a significantly greater reduction in bilirubin levels than MARS. Reductions in bile acid levels were similar for SPAD and MARS. When operating MARS in continuous veno-venous hemodialysis mode, as recommended by the manufacturer, no significant differences in the removal of bilirubin, bile acids, urea, and creatinine were found. However, MARS in continuous veno-venous hemodialysis mode was significantly less efficient in removing ammonia than MARS in CVVHDF mode. In conclusion, the detoxification capacity of SPAD is similar to or even greater than that of MARS. (HEPATOLOGY 2004;39:1408-1414.)