TY  - JOUR
A1  - Projahn, Delia
A1  - Simsekyilmaz, Sakine
A1  - Singh, Smriti
A1  - Kanzler, Isabella
A1  - Kramp, Birgit K.
A1  - Langer, Marcella
A1  - Burlacu, Alexandrina
A1  - Bernhagen, Jürgen
A1  - Klee, Doris
A1  - Zernecke, Alma
A1  - Hackeng, Tilman M.
A1  - Groll, Jürgen
A1  - Weber, Christian
A1  - Liehn, Elisa A.
A1  - Koenen, Roy R.
T1  - Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction
JF  - Journal of Cellular and Molecular Medicine
N2  - Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.
KW  - chemokines
KW  - therapy
KW  - cardiovascular pharmacology
KW  - remodelling
KW  - endothelial progenitor cells
KW  - left-ventricular function
KW  - heart-failure
KW  - rat model
KW  - recruitment
KW  - factor-I
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116597
SN  - 1582-4934
VL  - 18
IS  - 5
ER  - 
TY  - JOUR
A1  - Weissenberger, Manuel
A1  - Weissenberger, Manuela H.
A1  - Wagenbrenner, Mike
A1  - Heinz, Tizian
A1  - Reboredo, Jenny
A1  - Holzapfel, Boris M.
A1  - Rudert, Maximilian
A1  - Groll, Jürgen
A1  - Evans, Christopher H.
A1  - Steinert, Andre F.
T1  - Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer
JF  - PLoS One
N2  - Objective 
As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. 

Design 
Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX)9,transforming growth factor beta (TGFB) 1or bone morphogenetic protein (BMP) 2cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. 

Results 
Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenesSOX9,TGFB1andBMP2as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). 

Conclusions 
Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factorsSOX9,TGFB1andBMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.
KW  - stem cells
KW  - in vitro
KW  - chondrogenic differentiation
KW  - repair
KW  - chondrocytes
KW  - transplantation
KW  - stimulation
KW  - scaffolds
KW  - defects
KW  - therapy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230494
VL  - 15
IS  - 8
ER  -