TY  - JOUR
A1  - Suliman, Salwa
A1  - Mustafa, Kamal
A1  - Krueger, Anke
A1  - Steinmüller-Nethl, Doris
A1  - Finne-Wistrand, Anna
A1  - Osdal, Tereza
A1  - Hamza, Amani O.
A1  - Sun, Yang
A1  - Parajuli, Himalaya
A1  - Waag, Thilo
A1  - Nickel, Joachim
A1  - Johannessen, Anne Christine
A1  - McCormack, Emmet
A1  - Costea, Daniela Elena
T1  - Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
JF  - Biomaterials
N2  - This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK\(^{Luc}\)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK\(^{Luc}\) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK\(^{Luc}\) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK\(^{Luc}\) both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK\(^{Luc}\) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK\(^{Luc}\), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
KW  - Bone morphogenetic protein-2
KW  - Sinus floor augmentation
KW  - Marrow stromal cells
KW  - Growth; BMP-2
KW  - Tumorigenicity
KW  - Biodegradable polymer scaffolds
KW  - Mandibular continuity defects
KW  - Squamous-cell carcinoma
KW  - In-vitro
KW  - Mesenchymal transition
KW  - BMP-2
KW  - Bone tissue engineering
KW  - Biocompatibility
KW  - Microenvironment
KW  - Oral squamous cell carcinoma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188287
VL  - 95
ER  - 
TY  - JOUR
A1  - Seher, Axel
A1  - Nickel, Joachim
A1  - Mueller, Thomas D.
A1  - Kneitz, Susanne
A1  - Gebhardt, Susanne
A1  - Meyer ter Vehn, Tobias
A1  - Schlunck, Guenther
A1  - Sebald, Walter
T1  - Gene expression profiling of connective tissue growth factor (CTGF) stimulated primary human tenon fibroblasts reveals an inflammatory and wound healing response in vitro
JF  - Molecular Vision
N2  - Purpose: 

The biologic relevance of human connective tissue growth factor (hCTGF) for primary human tenon fibroblasts (HTFs) was investigated by RNA expression profiling using affymetrix (TM) oligonucleotide array technology to identify genes that are regulated by hCTGF. 

Methods: 

Recombinant hCTGF was expressed in HEK293T cells and purified by affinity and gel chromatography. Specificity and biologic activity of hCTGF was confirmed by biosensor interaction analysis and proliferation assays. For RNA expression profiling HTFs were stimulated with hCTGF for 48h and analyzed using affymetrix (TM) oligonucleotide array technology. Results were validated by real time RT-PCR. 

Results: 

hCTGF induces various groups of genes responsible for a wound healing and inflammatory response in HTFs. A new subset of CTGF inducible inflammatory genes was discovered (e.g., chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-X-C motif] ligand 6 [CXCL6], interleukin 6 [IL6], and interleukin 8 [IL8]). We also identified genes that can transmit the known biologic functions initiated by CTGF such as proliferation and extracellular matrix remodelling. Of special interest is a group of genes, e.g., osteoglycin (OGN) and osteomodulin (OMD), which are known to play a key role in osteoblast biology. 

Conclusions: 

This study specifies the important role of hCTGF for primary tenon fibroblast function. The RNA expression profile yields new insights into the relevance of hCTGF in influencing biologic processes like wound healing, inflammation, proliferation, and extracellular matrix remodelling in vitro via transcriptional regulation of specific genes. The results suggest that CTGF potentially acts as a modulating factor in inflammatory and wound healing response in fibroblasts of the human eye.
KW  - Bone morphogenetic protein-2
KW  - Smooth-muscle-cells
KW  - Myofibroblast differentiation
KW  - TGF-beta
KW  - CYR61
KW  - Proliferation
KW  - Mechanisms
KW  - Apoptosis
KW  - Receptor
KW  - Cancer
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140189
VL  - 17
IS  - 08. Okt
ER  -