Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2)in vivo

Abstract

The data suggest that localized overexpression of FGF-2 enhances the repair of cartilage defects via stimulation of chondrogenesis, without adverse effects on the synovial membrane. These results may lead to the development of safe gene-based therapies for human articular cartilage defects.

Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis

“…Many studies have implied a potent anabolic effect of bFGF on cartilage homeostasis and suggested its use for cartilage regeneration and repair (Cuevas et al, 1988;Cucchiarini et al, 2005;Hiraide et al, 2005;Inoue et al, 2006;Kaul et al, 2006;Deng et al, 2007;Schmal et al, 2007;Stewart et al, 2007). For example, Hiraide et al documented cartilage repair in an in vivo model of rabbit knee degeneration using an adeno-associated virus (AAV) to transport the bFGF gene into knee synovial tissue.…”

“…In lapine articular cartilage, bFGF introduced via gene transfer was found to increase cell proliferation both in vitro and in vivo, suggesting its potential for repair and regeneration of cartilage defects (Kaul et al, 2006). Due to its proliferative capacity, several studies have identified bFGF as an anabolic factor in chondrogenesis and ECM homeostasis (Thompson et al, 1991;Kaul et al, 2006;Tsai et al, 2007).…”

Gene therapy for chondral and osteochondral regeneration: is the future now?

“…Chemical methods, employed in preclinical studies, form complexes with DNA and various macromolecules, including liposomes, cationic polysaccharide and non-liposomal lipid-based transfection [14][15][16][17][18][19][20][21]. They can deliver large genes and are easy to produce on a large scale.…”

“…Such genes are insulin-like growth factor 1 (IGF-1) [15-18, 20, 23, 25], transforming growth factor β (TGF-β) [14,26,27], bone morphogenetic proteins (BMPs) [20,22] and fibroblast growth factor 2 (FGF-2) [16,18,21]. Other genes belong to the transcription factors family, SRY-related HMG box (SOX) [24], the anti-inflammatory cytokine Interleukin 10 (IL10) [12] and cartilage oligomeric matrix protein (COMP), a ECM component [19] (Table 1).…”

“…7). The cell vehicles, with and without scaffolds, are MSCs of different origin [14, 17, 26, 27, 40-42, 46, 54, 55, 59, 61, 71-75, 77, 82], chondrocytes [16,21,44,59,61,62,70,83] and, to a lesser extent, fibroblasts [18,56]. In fewer cases vectors are implanted into scaffolds without cells as vehicles: the plasmid vector is supported by a collagen I sponge or complexed with bPEI-HA via a porous oligo[poly(ethylene glycol) fumarate] hydrogel scaffold [22,24] and adenoviral vector by DCBM [51] (Table 1).…”