TY  - JOUR
A1  - Fernandez-Robredo, P.
A1  - Sancho, A.
A1  - Johnen, S.
A1  - Recalde, S.
A1  - Gama, N.
A1  - Thumann, G.
A1  - Groll, J.
A1  - Garcia-Layana, A.
T1  - Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering
JF  - Journal of Ophtamology
N2  - Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein.
KW  - endothelial growth factor
KW  - pluripotent stem cells
KW  - subfoveal choroidal neovascularization
KW  - human bruchs membrane
KW  - ciliary neurotrophic factor
KW  - randomized clinical trial
KW  - dystrophic RCS rats
KW  - subretinal space
KW  - in-vitro
KW  - retinal pigment epithelium
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118004
SN  - 2090-0058
IS  - 510285
ER  - 
TY  - JOUR
A1  - Weissenberger, M.
A1  - Weissenberger, M. H.
A1  - Gilbert, F.
A1  - Groll, J.
A1  - Evans, C. H.
A1  - Steinert, A. F.
T1  - Reduced hypertrophy in vitro after chondrogenic differentiation of adult human mesenchymal stem cells following adenoviral SOX9 gene delivery
JF  - BMC Musculoskeletal Disorders
N2  - Background 
Mesenchymal stem cell (MSC) based-treatments of cartilage injury are promising but impaired by high levels of hypertrophy after chondrogenic induction with several bone morphogenetic protein superfamily members (BMPs). As an alternative, this study investigates the chondrogenic induction of MSCs via adenoviral gene-delivery of the transcription factor SOX9 alone or in combination with other inducers, and comparatively explores the levels of hypertrophy and end stage differentiation in a pellet culture system in vitro. 

Methods 
First generation adenoviral vectors encoding SOX9, TGFB1 or IGF1 were used alone or in combination to transduce human bone marrow-derived MSCs at 5 x 10\(^2\) infectious particles/cell. Thereafter cells were placed in aggregates and maintained for three weeks in chondrogenic medium. Transgene expression was determined at the protein level (ELISA/Western blot), and aggregates were analysed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy. 

Results 
SOX9 cDNA was superior to that encoding TGFB1, the typical gold standard, as an inducer of chondrogenesis in primary MSCs as evidenced by improved lacuna formation, proteoglycan and collagen type II staining, increased levels of GAG synthesis, and expression of mRNAs associated with chondrogenesis. Moreover, SOX9 modified aggregates showed a markedly lower tendency to progress towards hypertrophy, as judged by expression of the hypertrophy markers alkaline phosphatase, and collagen type X at the mRNA and protein levels. 

Conclusion 
Adenoviral SOX9 gene transfer induces chondrogenic differentiation of human primary MSCs in pellet culture more effectively than TGFB1 gene transfer with lower levels of chondrocyte hypertrophy after 3 weeks of in vitro culture. Such technology might enable the formation of more stable hyaline cartilage repair tissues in vivo.
KW  - Mesenchymal stem cell
KW  - Cartilage
KW  - SOX9
KW  - Gene therapy
KW  - Chondrogenesis
KW  - Hypertrophy
KW  - Adenovirus
KW  - Bone marrow
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229232
VL  - 20
ER  -