A Fibrin Glue Composition as Carrier for Nucleic Acid Vectors

Schillinger, Ulrike; Wexel, Gabriele; Hacker, Christian; Kullmer, Martin; Koch, Christian A.; Gerg, Michael; Vogt, Stephan; Ueblacker, Peter; Tischer, Thomas; Hensler, Daniel; Wilisch, Jonas; Aigner, J.; Walch, Axel; Stemberger, A.; Plank, Christian

doi:10.1007/s11095-008-9719-8

Cited by 49 publications

(37 citation statements)

References 49 publications

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“…For cartilage tissue engineering purposes, FG scaffolds with nonviral copolymer-protected polyethylenimine-DNA vectors achieved sustained release of the gene over 20-day period and successful in vitro transfection of human keratinocytes and rabbit articular chondrocytes. 28 Nonetheless, FG formulation for AAV2 delivery has not been optimized. The fibrinogen/thrombin concentration in the FG preparation has been shown to affect the structural properties of the scaffold, and in turn influence the proliferation rate and morphology of hMSCs.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that diluted FG produces a more open fibrin network compared with undiluted FG scaffolds, 27 and that FG can act as an efficient scaffold for gene delivery. [28][29][30] In the current study, we investigated the effect of different fibrinogen dilutions during the preparation of FG scaffold on the delivery of AAV2 and their early effects on human BM-MSC (hBM-MSC) chondrogenesis in vitro. The aim of this study was to test the hypotheses that diluted FG scaffolds will release more viral particles, result in higher transduction efficiency, and increase the chondrogenic potential of transduced hBM-MSCs.…”

Section: Introductionmentioning

confidence: 99%

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Release of Bioactive Adeno-Associated Virus from Fibrin Scaffolds: Effects of Fibrin Glue Concentrations

Lee

Haleem

Yao

et al. 2011

Tissue Engineering Part A

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Fibrin glue (FG) is used in a variety of clinical applications and in the laboratory for localized and sustained release of factors potentially important for tissue engineering. However, the effect of different fibrinogen concentrations on FG scaffold delivery of bioactive adeno-associated viruses (AAVs) has not been established. This study was performed to test the hypothesis that FG concentration alters AAV release profiles, which affect AAV bioavailability. Gene transfer efficiency of AAV-GFP released from FG was measured using HEK-293 cells. Bioactivity of AAV transforming growth factor-beta1 (TGF-b 1 ) released from FG was assessed using the mink lung cell assay, and by measuring induction of cartilage-specific gene expression in human mesenchymal stem cells (hMSCs). Nondiluted FG had longer clotting times, smaller pore sizes, thicker fibers, and slower dissolution rate, resulting in reduced release of AAV. AAV release and gene transfer efficiency was higher with 25% and 50% FG than with the 75% and 100% FG. AAV-TGF-b 1 released from dilute-FG transduced hMSCs, resulting in higher concentrations of bioactive TGF-b 1 and greater upregulation of cartilage-specific gene expression compared with hMSC from undiluted FG. This study, showing improved release, transduction efficiency, and chondrogenic effect on hMSC of bioactive AAV-TGF-b 1 released from diluted FG, provides information important to optimization of this clinically available scaffold for therapeutic gene delivery, both in cartilage regeneration and for other tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Release of Bioactive Adeno-Associated Virus from Fibrin Scaffolds: Effects of Fibrin Glue Concentrations

Lee

Haleem

Yao

et al. 2011

Tissue Engineering Part A

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“…Hence, it can be assumed that COPROGs are suited to be embedded both in the gel phase and the MBCP ™ solid phase of the GAMBA composite matrix (Figure 1 ). As described previously (31) COPROGs are assembled in aqueous suspension. Hence, we have determined in a fi rst step the maximum volume of water per weight of MBCP ™ that the granules can soak.…”

Section: Coprogs On Mbcp ™ ™mentioning

confidence: 99%

Gene activated matrices for bone and cartilage regeneration in arthritis

Plank

Eglin

Fahy

et al. 2012

European Journal of Nanomedicine

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The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientifi c and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform will implement a concept of spatiotemporal control of regenerative bioactivity on command and demand.

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“…In general, efficacy and specificity of delivery tools to target tumour sites are improving. These approaches include copolymer-protected vectors (Schillinger et al 2008), liposomal tools with tumour-targeting affinities (Templeton 2009) and viral vectors with enhanced anti-tumour properties (Alemany 2009). Thus, these findings point towards potential approaches to restore endogenous BMP levels in adrenocortical carcinoma cells for the modulation of their functional properties and malignant potential providing hope for a specific and potent therapy of ACC patients with reduced side effects in the future.…”

Section: Potential Therapeutic Implicationsmentioning

confidence: 99%

Role of bone morphogenetic proteins in adrenal physiology and disease

Johnsen¹,

Beuschlein²

2010

Journal of Molecular Endocrinology

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Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-b superfamily of ligands that impact on a multitude of biological processes including cell type specification, differentiation and organogenesis. Furthermore, a large body of evidence points towards important BMP-dependent mechanisms in tumorigenesis. In accordance with their diverse actions, BMPs have been demonstrated to serve as auto-, para-and endocrine modulators also in a number of hormonal systems. In this review, we highlight novel aspects of BMP-dependent regulatory networks that pertain to adrenal physiology and disease, which have been uncovered during recent years. These aspects include the role of BMP-dependent mechanism during adrenal development, modulating effects on catecholamine synthesis and steroidogenesis and dysregulation of BMP signalling in adrenal tumorigenesis. Furthermore, we summarize potential therapeutic approaches that are based on reconstitution of BMP signalling in adrenocortical tumour cells.

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A Fibrin Glue Composition as Carrier for Nucleic Acid Vectors

Cited by 49 publications

References 49 publications

Release of Bioactive Adeno-Associated Virus from Fibrin Scaffolds: Effects of Fibrin Glue Concentrations

Release of Bioactive Adeno-Associated Virus from Fibrin Scaffolds: Effects of Fibrin Glue Concentrations

Gene activated matrices for bone and cartilage regeneration in arthritis

Role of bone morphogenetic proteins in adrenal physiology and disease

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