Publications

Pioneering results were obtained over the years, thanks to our successful cooperation with medical, biological and technical institutes and research institutions.

Below you will find a selection of relevant publications.

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Purified granulocytes in extracorporeal cell therapy: A multifaceted approach to combat sepsis-induced immunoparalysis

Purified GC remain functional after 72h of storage and additional 24h in the circulating treatment model. Cytokine secretion patterns revealed a significant increase, especially between 10 and 24h of treatment. Extending treatment time holds promise for enhancing immune response against sepsis-induced immunoparalysis. These findings provide valuable insights for optimizing immune-targeted therapeutic interventions.

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Purified Granulocyte Concentrates from Buffy Coats with Extended Storage Time

GCs prepared from pooled buffy coats provide a precious alternative to granulocytes obtained from apheresis. Reduction of red blood cells and platelets by more than 90% extends the maximum shelf life of GCs from 24 h to 72 h. For a therapeutic dose of at least 1 × 1010 granulocytes, 15–20 buffy coats are required.

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Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study

The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.

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Prolonged storage of purified granulocyte concentrates: Introduction of a new purification method

A significant reduction in RBC (98%) through sedimentation, and platelets (96%) by washing, purified the white blood cell (WBC) population and enriched the granulocytes to 96% of the WBC in the pGC. After 72 h of storage, over 90% of the initial WBC count of pGC remained, was viable (≥97%), and the granulocytes exhibited a high phagocytosis and oxidative burst functionality, comparable to sGC after 24 h.

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Therapeutic apheresis in sepsis

Experimental extracorporeal cell treatment adds another approach to the field. Preliminary results include improved cellular immunocompetence, stabilized hemodynamics, and improved critical care scores.

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Extracorporeal therapy of sepsis by purified granulocyte concentrates: ex vivo circulation model

In this ex vivo study high functionality of immune cells was adequately preserved even after 3 days of storage and also in extracorporeal circuits with sepsis plasma. This is a promising indicator of the functionality of the technology and encourages further clinical studies.

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Extracorporeal immune cell therapy of sepsis: ex vivo results

Results demonstrate the suitability of a simplified extracorporeal system. Furthermore, granulocytes remain viable and highly active during a 6-h treatment even after storage for 3 days supporting the treatment of septic patients with this system in advanced clinical trials.

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Bioartificial Therapy of Sepsis: Changes of Norepinephrine-Dosage in Patients and Influence on Dynamic and Cell Based Liver Tests during Extracorporeal Treatments.

The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.

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Effects of Bioreactor-Oxygenation During Extracorporeal Granulocytes Treatment in Septic Patients.

Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The cells used were screened for functionality; blood gas, glucose and lactate levels were obtained from the circuit of the bioreactor. Five patients were treated with an oxygenator setup (oxy group), five without an oxygenator (non-oxy group).

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Extracorporeal cell therapy with granulocytes in a pig model of Gram-positive sepsis.

Extracorporeal therapy with granulocytic cells significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.

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Plasma Separation by Centrifugation and Subsequent Plasma Filtration: Impact on Survival in a Pig Model of Sepsis.

Extracorporeal therapy with online centrifugation and plasma filtration significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.

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Role of different replacement fluids during extracorporeal treatment in a pig model of sepsis.

Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.

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Use of preconditioned human phagocytes for extracorporeal adsorption of viruses.

This article discusses the possibility of using preconditioned human phagocytes in an extracorporeal system to adsorb viral pathogens. Data are presented from in vitro experiments. Adsorption of an enterovirus and hepatitis B virus (HBV) was tested by a preconditioned human promyelocyte cell line.

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Safety Evaluation for a Cell‐based Immune Support System in an Ex Vivo Rat Model of Gram‐negative Sepsis.

The study assessed the safety of an extracorporeal immune support system with granulocyte cells in a rat model of Gram-negative sepsis. The data suggested that the extracorporeal use of granulocytes enables the therapeutic use of these cells, while avoiding adverse effects due to direct contact with internal organs.

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Use of Human Preconditioned Phagocytes for Extracorporeal Immune Support: Introduction of a Concept.

In this paper, the authors discussed the possibility of using preconditioned cells in an extracorporeal biohybrid immune support system. Extracorporeal bioreactor experiments seem to be feasible to test the benefit in immunoparalysis‐associated diseases like SIRS or sepsis.

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Impaired Cell Viability and Functionality of Hepatocytes after Incubation with Septic Plasma-Results of a Second Prospective Biosensor Study.

It is a second prospective study with 99 septic patients to test a new cell-based cytotoxicity device (biosensor) and to assess the clinical relevance for the early detection of liver dysfunction and prognostic capacity. The biosensor may be an early detection tool for hepatic dysfunction in septic patients and could be of prognostic relevance.

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Impaired cell functions of hepatocytes incubated with plasma of septic patients.

In a prospective clinical experimental study, the hepatotoxicity of plasma from septic and non-septic patients was tested. The plasma from patients with septic shock impaired the cell functions of HepG2 / C3A cells.

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Neutrophil-derived circulating free DNA (cf-DNA/NETs), a potential prognostic marker for mortality in patients with severe burn injury.

The authors discussed the predictive potential of cf-DNA/NETs for mortality in patients with severe burn injury. cf-DNA/NETs seems to be a rapid, valuable marker for prediction of mortality in burn patients.

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Kynurenine Inhibits Chondrocyte Proliferation and Is Increased in Synovial Fluid of Patients with Septic Arthritis

Septic arthritis is associated with significantly increased values of synovial kynurenine. Furthermore, kynurenine inhibits proliferation of chondrocytes, which strongly suggests a pathophysiological effect of kynurenine on cartilage in inflammatory arthropathies.

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The clinical value of neutrophil extracellular traps.

This review summarizes current knowledge about the relation of NETs in a broad spectrum of clinical settings. Specifically, the authors focused on the importance of NETs as a predictive marker in severely ill patients. In addition, authors discussed the potential pathophysiology of NETs.

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Increased Plasma Kynurenine Values and Kynurenine-Tryptophan Ratios After Major Trauma Are Early Indicators for the Development of Sepsis.

Both increased kynurenine values and kynurenine-tryptophan ratios predicted posttraumatic development of sepsis and organ failure. This ought to be validated in subsequent studies.

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Neutrophil-derived Circulating Free DNA (cf-DNA/NETs): A Potential Prognostic Marker for Posttraumatic Development of Inflammatory Second Hit and Sepsis.

Circulating free DNA/NETs seems to be a valuable additional marker for the calculation of injury severity and/or prediction of inflammatory second hit on ICU. However, a large clinical trial with severely injured patients should confirm the prognostic value of neutrophil-derived cf-DNA/NETs.

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Diagnostic accuracy of neutrophil‐derived circulating free DNA (cf‐DNA/NETs) for septic arthritis.

cf-DNA/NETs seem to be a valuable additional marker for the diagnosis of septic arthritis or periprosthetic infections. However, this result should be confirmed in a large clinical trial.

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