TY  - JOUR
A1  - Ramachandran, Sarada Devi
A1  - Schirmer, Katharina
A1  - Münst, Bernhard
A1  - Heinz, Stefan
A1  - Ghafoory, Shahrouz
A1  - Wölfl, Stefan
A1  - Simon-Keller, Katja
A1  - Marx, Alexander
A1  - Øie, Cristina Ionica
A1  - Ebert, Matthias P.
A1  - Walles, Heike
A1  - Braspenning, Joris
A1  - Breitkopf-Heinlein, Katja
T1  - In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells
JF  - PLoS One
N2  - In this study we used differentiated adult human upcyte (R) cells for the in vitro generation of liver organoids. Upcyte (R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte (R) process). Proliferating upcyte (R) cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte (R) cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel\(^{TM}\), they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.
KW  - adults
KW  - enzyme metabolism
KW  - albumins
KW  - primary cells
KW  - induction
KW  - expression
KW  - human heptocytes
KW  - mesenchymal stem cells
KW  - oragnoids
KW  - heptaocytes
KW  - drug metabolism
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139552
VL  - 10
IS  - 10
ER  - 
TY  - JOUR
A1  - Cheng, Cheng
A1  - MacIntyre, Lynsey
A1  - Ramadan Abdelmohsen, Usama
A1  - Horn, Hannes
A1  - Polymenakou, Paraskevi N.
A1  - Edrada-Ebel, RuAngelie
A1  - Hentschel, Ute
T1  - Biodiversity, Anti-Trypanosomal Activity Screening, and Metabolomic Profiling of Actinomycetes Isolated from Mediterranean Sponges
JF  - PLoS One
N2  - Marine sponge–associated actinomycetes are considered as promising sources for the discovery of novel biologically active compounds. In the present study, a total of 64 actinomycetes were isolated from 12 different marine sponge species that had been collected offshore the islands of Milos and Crete, Greece, eastern Mediterranean. The isolates were affiliated to 23 genera representing 8 different suborders based on nearly full length 16S rRNA gene sequencing. Four putatively novel species belonging to genera Geodermatophilus, Microlunatus, Rhodococcus and Actinomycetospora were identified based on a 16S rRNA gene sequence similarity of < 98.5% to currently described strains. Eight actinomycete isolates showed bioactivities against Trypanosma brucei brucei TC221 with half maximal inhibitory concentration (IC50) values <20 μg/mL. Thirty four isolates from the Milos collection and 12 isolates from the Crete collection were subjected to metabolomic analysis using high resolution LC-MS and NMR for dereplication purposes. Two isolates belonging to the genera Streptomyces (SBT348) and Micromonospora (SBT687) were prioritized based on their distinct chemistry profiles as well as their anti-trypanosomal activities. These findings demonstrated the feasibility and efficacy of utilizing metabolomics tools to prioritize chemically unique strains from microorganism collections and further highlight sponges as rich source for novel and bioactive actinomycetes.
KW  - streptomyces
KW  - drug metabolism
KW  - metabolites
KW  - ribosomal RNA
KW  - metabolomics
KW  - actinobacteria
KW  - sponges
KW  - secondary metabolites
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125138
VL  - 10
IS  - 9
ER  -