Jungebluth P.,Karolinska Institutet |
Luedde M.,University of Kiel |
Ferrer E.,University of Barcelona |
Luedde T.,RWTH Aachen |
And 13 more authors.
Cell Transplantation | Year: 2011
Because human lungs are unlikely to repair or regenerate beyond the cellular level, cell therapy has not previously been considered for chronic irreversible obstructive lung diseases. To explore whether cell therapy can restore lung function, we administered allogenic intratracheal mesenchymal stem cells (MSCs) in the trachea of rats with chronic thromboembolic pulmonary hypertension (CTEPH), a disease characterized by single or recurrent pulmonary thromboembolic obliteration and progressive pulmonary vascular remodeling. MSCs were retrieved only in high pressure-exposed lungs recruited via a homing stromal derived factor-1α/ CXCR4 pathway. After MSC administration, a marked and long-lasting improvement of all clinical parameters and a significant change of the proteome level were detected. Beside a variation of liver proteome, such as caspase-3, NF-κB, collagen1A1, and α-SMA, we also identified more than 300 resident and nonresident lung proteins [e.g., myosin light chain 3 (P16409) or mitochondrial ATP synthase subunit alpha (P15999)]. These results suggest that cell therapy restores lung function and the therapeutic effects of MSCs may be related to protein-based tissue reconstituting effects. © 2011 Cognizant Comm. Corp.
Giri S.,Biomedical Biotechnological Center |
Nieber K.,University of Leipzig |
Acikgoz A.,Biomedical Biotechnological Center |
Pavlica S.,Biomedical Biotechnological Center |
And 2 more authors.
Molecular and Cellular Biochemistry | Year: 2010
Presently, there is growing interest on telomerase activity in all cells (somatic cells, stem cells, cancerous cells and others) since this activity is associated with cellular changes such as proliferation, differentiation, immortalization, cell injury and ageing. Telomerase activity is absent in most of the somatic cells but present in over 90% of cancerous cells and other immortalized cell lines. In our present study, we cultured a rat embryonal liver progenitor cell line RLC-18 in a self-assembly nanostructured scaffold-coated bioreactor (NCB), collagen-coated plates (CCP) and uncoated plates (UP), and evaluated changes of telomerase activity by non radioactive techniques (Telo TAGGG Telomerase PCR ELISA, cell proliferation based on mitochondria number by MTT assay and hepatic functions such as albumin secretion, urea metabolism, Cytochrome P450 activity like ethoxyresorufin-O-deethylase (EROD) activity. We found less telomerase activity and less cell proliferation, but more hepatic functions on the NCB than on the CCP and UP. Our data support the concept that cell-scaffold interaction may play a significant in controlling the telomerase activity as well as enhanced hepatic functions. Although our present study does not focus on the exact mechanism of telomerase regulation, our result may provide basic clues on cell differentiation whereby telomerase activity inhibits differentiation of cells as in the rat embryonic liver cell line, may be regulated by cell-scaffold interaction and where there is less proliferation, cells perform enhanced hepatic functions, thereby implying that bioartificial liver support may be possible. © 2009 Springer Science+Business Media, LLC.
PubMed | Biomedical Biotechnological Center
Type: Journal Article | Journal: Expert opinion on drug metabolism & toxicology | Year: 2010
IMPORTANCE OF THE FILED: According to a 2006 survey report of pharmaceutical companies, hepatotoxicity was ranked first in terms of adverse events and it remains the most common reason for restriction or withdrawal of a drug from the market by the FDA. Although there are many reasons underlying drug-induced hepatotoxicity, one of the most important is hepatotoxicity induced by drug metabolites.This review highlights the unexpected evidence showing that > 64 allopathic drugs out of 900 can induce potentially life-threatening hepatotoxicity with diverse clinical features. In parallel, we demonstrate the use of a two-compartment organotypical model for monitoring drug biotransformation and the status of parent drugs or drug metabolites (reactive or stable metabolites).The reader will gain knowledge of the importance of the two-compartment model with special reference to drug metabolites and become aware of the hepatotoxicity of a list of allopathic drugs, many of which are presently used without prescription.A central challenge regarding drug-induced hepatotoxicity is to understand drug metabolite formation because, although many parent drugs are not toxic, their metabolites can be toxic to liver cells following biotransformation.