Fibrin Sealants from Fresh or Fresh/Frozen Plasma as Scaffolds for<i>In Vitro</i>Articular Cartilage Regeneration

Dare, Emma V.; Griffith, May; Poitras, Philippe; Wang, Tao; Dervin, Geoffrey F.; Giulivi, Antonio; Hincke, Maxwell T.

doi:10.1089/ten.tea.2008.0228

Cited by 31 publications

(26 citation statements)

References 51 publications

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“…Absorbance was measured on a multi-well plate reader and compared to a plot of standards prepared from purified chondroitin-4-sulphate (derived from bovine trachea) [36].…”

Section: Methodsmentioning

confidence: 99%

Evidence for Regulated Interleukin-4 Expression in Chondrocyte-Scaffolds under In Vitro Inflammatory Conditions

et al. 2011

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ObjectiveTo elucidate the anti-inflammatory and anabolic effects of regulated expression of IL-4 in chondrocyte-scaffolds under in vitro inflammatory conditions.MethodsMature articular chondrocytes from dogs (n = 3) were conditioned through transient transfection using pcDNA3.1.cIL-4 (constitutive) or pCOX-2.cIL-4 (cytokine-responsive) plasmids. Conditioned cells were seeded in alginate microspheres and rat-tail collagen type I matrix (CaReS®) to generate two types of tissue-engineered 3-dimensional scaffolds. Inflammatory arthritis was simulated in the packed chondrocytes through exogenous addition of recombinant canine (rc) IL-1β (100 ng/ml) plus rcTNFα (50 ng/ml) in culture media for 96 hours. Harvested cells and culture media were analyzed by various assays to monitor the anti-inflammatory and regenerative (anabolic) properties of cIL-4.ResultscIL-4 was expressed from COX-2 promoter exclusively on the addition of rcIL-1β and rcTNFα while its expression from CMV promoter was constitutive. The expressed cIL-4 downregulated the mRNA expression of IL-1β, TNFα, IL-6, iNOS and COX-2 in the cells and inhibited the production of NO and PGE2 in culture media. At the same time, it up-regulated the expression of IGF-1, IL-1ra, COL2a1 and aggrecan in conditioned chondrocytes in both scaffolds along with a diminished release of total collagen and sGAG into the culture media. An increased amount of cIL-4 protein was detected both in chondrocyte cell lysate and in concentrated culture media. Neutralizing anti-cIL-4 antibody assay confirmed that the anti-inflammatory and regenerative effects seen are exclusively driven by cIL-4. There was a restricted expression of IL-4 under COX-2 promoter possibly due to negative feedback loop while it was over-expressed under CMV promoter (undesirable). Furthermore, the anti-inflammatory /anabolic outcomes from both scaffolds were reproducible and the therapeutic effects of cIL-4 were both scaffold- and promoter-independent.ConclusionsRegulated expression of therapeutic candidate gene(s) coupled with suitable scaffold(s) could potentially serve as a useful tissue-engineering tool to devise future treatment strategies for osteoarthritis.

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“…Absorbance was measured on a multi-well plate reader and compared to a plot of standards prepared from purified chondroitin-4-sulphate (derived from bovine trachea) [36].…”

Section: Methodsmentioning

confidence: 99%

Evidence for Regulated Interleukin-4 Expression in Chondrocyte-Scaffolds under In Vitro Inflammatory Conditions

et al. 2011

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“…A fibrin‐based hydrogel was selected for this application because fibrinogen is readily available, simple to use, biocompatible and can be combined with other biological substrates4–6. Stock solutions of bovine fibrinogen (40 mg/ml; Cat.…”

Section: Methodsmentioning

confidence: 99%

Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung

Ingenito

Şen

Tsai

et al. 2009

J Tissue Eng Regen Med

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This study summarizes the development and testing of a scaffold to promote engraftment of cells in the distal lung. A fibrinogen-fibronectin-vitronectin hydrogel (FFVH) was developed and optimized with respect to its mechanical and biological properties for this application. In vitro, FFVH scaffolds promoted attachment, histiotypic growth and expression of basement membrane proteins by primary ovine lung mesenchymal cells derived from lung biopsies. In vivo testing was then performed to assess the ability of FFVHs to promote cell engraftment in the sheep lung. Treatment with autologous cells delivered using FFVH was clinically well tolerated. Cells labelled with a fluorescent dye (PKH-26) were detected at treatment sites after 1 month. Tissue mass (assessed by CT imaging) and lung perfusion (assessed by nuclear scintigraphy) were increased at emphysema test sites. Post-treatment histology demonstrated cell proliferation and increased elastin expression without scarring or collapse. No treatment-related pathology was observed at healthy control sites. FFVH scaffolds promote cell attachment, spreading and extracellular matrix expression in vitro and apparent engraftment in vivo, with evidence of trophic effects on the surrounding tissue. Scaffolds of this type may contribute to the development of cell-based therapies for patients with end-stage pulmonary diseases.

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“…64,66 MSCs differentiated into chondrocytes and produced more cartilage tissue when encapsulated in fibrin hydrogels when compared to alginate hydrogels. 67 Fibrin hydrogels have poor mechanical properties, 64,65 but they have been investigated as carriers in autologous chondrocyte transplantation in clinical trials in Europe (Tissucol). 63 Hyaluronan: Hyaluronan is a natural glycosaminoglycan found in articular cartilage and synovial fluid and is also involved in the regulation of wound healing, cell motility, ECM organization, and cell differentiation.…”

Section: Type Of Polymermentioning

confidence: 99%

Hydrogels for the Repair of Articular Cartilage Defects

Spiller

Maher

Lowman

2011

Tissue Engineering Part B: Reviews

400

312

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Fibrin Sealants from Fresh or Fresh/Frozen Plasma as Scaffolds forIn VitroArticular Cartilage Regeneration

Cited by 31 publications

References 51 publications

Evidence for Regulated Interleukin-4 Expression in Chondrocyte-Scaffolds under In Vitro Inflammatory Conditions

Evidence for Regulated Interleukin-4 Expression in Chondrocyte-Scaffolds under In Vitro Inflammatory Conditions

Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung

Hydrogels for the Repair of Articular Cartilage Defects

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