rAAV-mediated overexpression of FGF-2 promotes cell proliferation, survival, and α-SMA expression in human meniscal lesions

Cucchiarini, Magali; Schetting, Sarah; Terwilliger, Ernest F.; Kohn, Dieter; Madry, Henning

doi:10.1038/gt.2009.91

Cited by 53 publications

(123 citation statements)

References 57 publications

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“…Viral overexpression of FGF-2 in chondrocytes has been demonstrated to stimulate proliferation in vitro as well as improved tissue repair when transfected cells are delivered in vivo Yokoo et al, 2005;Kaul et al, 2006). Further, the combination of FGF-2 and Sox9 overexpression in human OA chondrocytes stimulated mitogenesis, stimulated GAG and collagen type II deposition, and inhibited cellular hypertrophy (Cucchiarini et al, 2009). Alternatively, the overexpression of antiapoptotic Bcl-2 (Surendran et al, 2006), or the serine proteinase inhibitor kallistatin, offers a means by which native chondrocytes can be protected from OA-induced cell death (Wang et al, 2005;Hsieh et al, 2009).…”

Section: Gene Therapy For Osteoarthritismentioning

confidence: 99%

Mesenchymal Stem Cells and Osteoarthritis: Remedy or Accomplice?

et al. 2010

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Section: Gene Therapy For Osteoarthritismentioning

confidence: 99%

Mesenchymal Stem Cells and Osteoarthritis: Remedy or Accomplice?

et al. 2010

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“…Adenoviral vectors are immunogenic and do not integrate into the host cell genome; as a consequence they prevent the risk of cancer but they do not grant longterm transgene expression (Madry et al, 2004;Steinert et al, 2007). Adeno-associated vectors (AAV) can carry only a small amount of DNA; on the other hand, they are not immunogenic and not pathogenic, and they can transduce non-dividing cells: these features make them very attractive for orthopaedic use, making them a promising option for the treatment of musculoskeletal diseases (Madry et al, 2004;Cucchiarini et al, 2009).…”

Section: Growth Factors and Gene Therapymentioning

confidence: 99%

“…Following the first studies with marker genes (Madry et al, 2004;Goto et al, 1999), the main GF used for gene transfer to the meniscus to date are HGF (Hidaka et al, 2002), TGF-β1 (Steinert et al, 2007), and FGF-2 (Cucchiarini et al, 2009). HGF induced blood vessel formation in an engineered construct made of meniscal fibrochondrocytes seeded onto a PGA scaffold, improving the potential for integration and metabolic exchanges of the engineered implant (Hidaka et al, 2002).…”

Section: Growth Factors and Gene Therapymentioning

confidence: 99%

“…Consequently, a localised delivery of TGF-β1 to the site of lesion is mandatory. FGF-2 transfer through an AAV resulted in increased proliferation, survival and metabolic activity of human MC in vitro, in a three-dimensional in vitro culture system, and in situ in a human meniscal defect model (Cucchiarini et al, 2009). This study proved that direct application of AAV vectors has the potential to induce healing in the injured meniscus.…”

Section: Growth Factors and Gene Therapymentioning

confidence: 99%

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Meniscus repair and regeneration: review on current methods and research potential

Scotti

Hirschmann

Antinolfi

et al. 2013

eCM

126

123

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Meniscus regeneration is an unsolved clinical challenge. Despite the wide acceptance of the degenerative consequences of meniscectomy, no surgical procedure has succeeded to date in regenerating a functional and long-lasting meniscal fibrocartilage. Research proposed a number of experimental approaches encompassing all the typical strategies of regenerative medicine: cellfree scaffolds, gene therapy, intra-articular delivery of progenitor cells, biological glues for enhanced bonding of reparable tears, partial and total tissue engineered meniscus replacement. None of these approaches has been completely successful and can be considered suitable for all patients, as meniscal tears require specific and patientrelated treatments depending on the size and type of lesion. Recent advances in cell biology, biomaterial science and bioengineering (e.g., bioreactors) have now the potential to drive meniscus regeneration into a series of clinically relevant strategies. In this tutorial paper, the clinical need for meniscus regeneration strategies will be explained, and past and current experimental studies on meniscus regeneration will be reported.

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“…To aid healing of torn menisci, investigators are now examining the potential of growth factor therapy. Primary candidates among these are basic fibroblast growth factor bFGF [4], TGF-β [5,6] and platelet derived growth factor-AB. Previous studies have indicated a dramatic, order-of-magnitude effect on meniscal cell proliferation with exogenous bFGF in monolayer culture [4].…”

Section: Introductionmentioning

confidence: 99%

The Knee Joint Tissues Differ Significantly in TGFβ1 Expression and Its Sensitivity

Fulzele¹,

Hunter²,

Sangani³

et al. 2013

CellBio

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The knee joint is the largest and most complex joint in the human body. In this study, we investigated TGFβ1 expression in the outer meniscus, inner meniscus and articular cartilage of rabbit and human knee tissue (outer and inner menisci) in order to determine the potential role of this factor in normal meniscal function. We also examined the potential of TGF-β1 stimulation to promote tissue regeneration in the two different regions of rabbit knee meniscus tissue. Immunohistochemical investigations of TGF-β1 were performed on rabbit and human knee tissue. The rabbit outer, inner and articular cartilage cells were culture and stimulated with TGF-β1 followed by cell proliferation assay and extracellular matrix analysis. Regulatory studies were performed using TGF-β1 inhibitors SB-431542 and PD98059. Gene expression was analyzed by quantitative polymerase chain reaction. We found marked regional variation in the expression of TGF-β1 in rabbit and human knee. TGF-β1 expressions are relatively greater in the outer meniscus than inner meniscus. Furthermore, we found that exogenous TGF-β1 stimulation increased cell proliferation and aggrecan synthesis more so in the outer than in the inner meniscus. Articular cartilage tissue shows moderate levels of cell proliferation and ECM synthesis when compared with outer and inner meniscus. These findings suggest that growth factors used to enhance the repair and regeneration of meniscal tissue should be tailored to enhance region-specific variation in cell proliferation and extracellular matrix synthesis.

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rAAV-mediated overexpression of FGF-2 promotes cell proliferation, survival, and α-SMA expression in human meniscal lesions

Cited by 53 publications

References 57 publications

Mesenchymal Stem Cells and Osteoarthritis: Remedy or Accomplice?

Mesenchymal Stem Cells and Osteoarthritis: Remedy or Accomplice?

Meniscus repair and regeneration: review on current methods and research potential

The Knee Joint Tissues Differ Significantly in TGFβ1 Expression and Its Sensitivity

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