Diseases desperate grown
By desperate appliance are relieved,
Or not at all.
William Shakespeare Hamlet Act IV, Scene 3
By desperate appliance are relieved,
Or not at all.
William Shakespeare Hamlet Act IV, Scene 3
Liver Cell Transplantation
Liver transplantation (LTx) is the gold standard for treatment of end-stage liver diseases and liver-based metabolic disorders, but availability is restricted by the shortage of donor organs. Liver cell transplantation (LCT) was developed to enable treatment of multiple patients with cells obtained from one donor organ and to provide alternatives in cases with contraindications for major surgery, i.e., LTx. While initial clinical studies demonstrated the safety and efficacy of LCT, success remained limited since LCT could not achieve the outcomes required for it to be established as a standard medical treatment. As part of further clinical studies on improvement of LCT, strategies for non-invasive monitoring of transplanted cells are under investigation.
Liver transplantation (LTx) is the gold standard for treatment of end-stage liver diseases and liver-based metabolic disorders, but availability is restricted by the shortage of donor organs. Liver cell transplantation (LCT) was developed to enable treatment of multiple patients with cells obtained from one donor organ and to provide alternatives in cases with contraindications for major surgery, i.e., LTx. While initial clinical studies demonstrated the safety and efficacy of LCT, success remained limited since LCT could not achieve the outcomes required for it to be established as a standard medical treatment. As part of further clinical studies on improvement of LCT, strategies for non-invasive monitoring of transplanted cells are under investigation.
microRNA and the Liver
After liver surgery, the lost functional mass is replaced in a process of compensatory growth in which quiescent hepatocytes reenter the cell cycle. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small noncoding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration.
miRNAs are the most abundant class of small, endogenous noncoding RNAs. miRNAs inhibit protein synthesis by blocking translation via complementary binding of messenger RNA (mRNA) or by suppressing translation and the subsequent degradation of target mRNA. miRNAs act in a variety of cellular processes such as development, organ homeostasis, and cancer.
After liver surgery, the lost functional mass is replaced in a process of compensatory growth in which quiescent hepatocytes reenter the cell cycle. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small noncoding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration.
miRNAs are the most abundant class of small, endogenous noncoding RNAs. miRNAs inhibit protein synthesis by blocking translation via complementary binding of messenger RNA (mRNA) or by suppressing translation and the subsequent degradation of target mRNA. miRNAs act in a variety of cellular processes such as development, organ homeostasis, and cancer.
Hepatocyte Isolation & Culture
Some promising therapeutic approaches in Regenerative Medicine, namely extracorporeal liver support and liver cell transplantation, are based on the use of primary human liver cells in order to support or replace the liver function. Various studies have been directed towards the development of methods for the storage and the effective cryopreservation of primary human liver cells. The successful establishment of methods for the long-term storage of human hepatocytes would largely facilitate the therapeutic usage of the cells, considering the irregular availability of human liver tissue. Current cryopreservation techniques need to be optimized in order to establish suitable conditions for freezing, thawing and subsequent culture or transplantation of human hepatocytes.
Some promising therapeutic approaches in Regenerative Medicine, namely extracorporeal liver support and liver cell transplantation, are based on the use of primary human liver cells in order to support or replace the liver function. Various studies have been directed towards the development of methods for the storage and the effective cryopreservation of primary human liver cells. The successful establishment of methods for the long-term storage of human hepatocytes would largely facilitate the therapeutic usage of the cells, considering the irregular availability of human liver tissue. Current cryopreservation techniques need to be optimized in order to establish suitable conditions for freezing, thawing and subsequent culture or transplantation of human hepatocytes.
NeoHybrid Liver Graft
The neo-hybrid Liver Graft, an in vivo tissue engineered liver graft using autologous hepatocytes and hepatic progenitors cells, is a novel approach that might reduce the need for immunosuppression, improve long-term outcome after liver transplantation (LTx) and possibly induce host tolerance to allografts. Adult liver cells and autologous hepatic progenitors will be isolated from the diseased liver, explanted during standard orthotopic LTx, and retransplanted to the recipient via the spleen. The allogeneic liver graft is serving as a biological matrix for the engraftment of the autologous cells. Once these cells have engrafted, it is postulated that the autologous cells will repopulate the allogeneic graft liver as they have a selective advantage over the donor tissue due to their autologous origin.
The neo-hybrid Liver Graft, an in vivo tissue engineered liver graft using autologous hepatocytes and hepatic progenitors cells, is a novel approach that might reduce the need for immunosuppression, improve long-term outcome after liver transplantation (LTx) and possibly induce host tolerance to allografts. Adult liver cells and autologous hepatic progenitors will be isolated from the diseased liver, explanted during standard orthotopic LTx, and retransplanted to the recipient via the spleen. The allogeneic liver graft is serving as a biological matrix for the engraftment of the autologous cells. Once these cells have engrafted, it is postulated that the autologous cells will repopulate the allogeneic graft liver as they have a selective advantage over the donor tissue due to their autologous origin.
Artificial and Bioartificial Liver Support
Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and patients waiting for transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation and to develop extracorporeal methods to support or replace the function of the failing organ. Over the past 20 years many liver support concepts have been developed and evaluated. Despite these efforts, none of the devices — neither, cell-based nor cell-free — were able to fully meet clinical demands. These limited results generate questions: Are the concepts evaluated inadequately? Are the concepts right but their scale too small and performances too low?
Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and patients waiting for transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation and to develop extracorporeal methods to support or replace the function of the failing organ. Over the past 20 years many liver support concepts have been developed and evaluated. Despite these efforts, none of the devices — neither, cell-based nor cell-free — were able to fully meet clinical demands. These limited results generate questions: Are the concepts evaluated inadequately? Are the concepts right but their scale too small and performances too low?
SlideReactor
Most bioartificial liver support systems are based on hollow fiber capillaries within modified dialysis cartridges or more sophisticated bioreactor constructions. Due to their design microscopic follow-up of re-organization and growth of tissue between the hollow fibers is not possible.The SlideReactor is a simple hollow fiber based bioreactor construction suitable for light microscopy and time-lapse video observation. The device enables the characterization of cell behavior under controlled conditions and the analysis of the influence of medium supplements on the cell viability and tissue integrity. It may be useful for the comparison of different types of hollow fibers, e.g. for future use in bioreactor-based extracorporeal liver assist devices.
Most bioartificial liver support systems are based on hollow fiber capillaries within modified dialysis cartridges or more sophisticated bioreactor constructions. Due to their design microscopic follow-up of re-organization and growth of tissue between the hollow fibers is not possible.The SlideReactor is a simple hollow fiber based bioreactor construction suitable for light microscopy and time-lapse video observation. The device enables the characterization of cell behavior under controlled conditions and the analysis of the influence of medium supplements on the cell viability and tissue integrity. It may be useful for the comparison of different types of hollow fibers, e.g. for future use in bioreactor-based extracorporeal liver assist devices.
Latest News...
- Following the exceptionally successful meetings in Boston, Sydney and Vancouver, we would like to welcome you to the 24th International Congress of The Transplantation Society.
More information via www.transplantation2012.org !
- As a first result of our latest projects concerning the role of miRNA in liver regeneration the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology has accepted our paper "Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy"
- Nora Kammer's paper in Artificial Organs on "Labelling of primary human hepatocytes with micron-sized iron oxide particles in suspension culture suitable for large-scale preparation" is available. The studies showed that labelling in suspension is a practicable method for fast and efficient preparation of large numbers of labelled cells that are suitable for clinical applications.
- The XXXIX Congress of the European Society for Artificial Organs (ESAO 2012) will be held in Rostock, Germany, September 26th-29th, 2012. The motto of the ESAO Congress 2012 will be "from replacement to regeneration – from science to clinic".
More information via the official webpage. - Our latest paper on "Monitoring of liver cell transplantation in a preclinical swine model using magnetic resonance imaging" has been accepted for publication in CELL MEDICINE. 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.
- SlideReactor was starlet at exhibition “WeltWissen. 300 Years of Science in Berlin”
A multicompartment SlideReactor is shown at the exhibition “WeltWissen – World Knowledge”. SlideReactor at “WeltWissen – World Knowledge”. The exhibition was the high point of the Berlin Year of Science.
More information via www.weltwissen-berlin.de !
We thank the Deutsche Forschungsgemeinschaft (German Research Fondation, DFG), the Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research, BMBF), the European Region Development Fund (EFRE) and the Fiebig-Stiftung for their financial support.
