Table 2.
Growth factors and receptors.
| References | Objectives | Study design | Disease models | Delivery methods | Targets | Effects |
|---|---|---|---|---|---|---|
| Manning et al. (45) | Evaluate co-expression of IGF-1 and IL-4 in an in vitro inflammatory model | Preclinical in vitro | IL-1β /TNF-α-stimulated canine chondrocytes | pVitro2-IGF-1; pVitro2-IGF-1/IL-4 (transfection with Fugene6) | IGF-1 and IL-4 | Reduced pro-inflammatory mediators and IGF-binding proteins; increased type II collagen and proteoglycans |
| Weimer et al. (46) | Investigate efficient and prolonged IGF-I overexpression via rAAV transfection and its effect on restoring OA cartilage | Preclinical in vitro and in situ | Human OA chondrocyte monolayer cultures and alginate spheres; human OA explant cultures | Adenoassociated virus: rAAV-hIGF-I | IGF-I | Increased proliferation; decreased apoptosis; increased levels of proteoglycan and type II collagen; increased cell proliferation in situ; decreased apoptosis in situ; increased proteoglycan and type II collagen content in situ |
| Aguilar et al. (47) | Determine efficiency of pAAV/IGF-I transfection of chondrocytes and determine effect of endogenous vs. exogenous IGF-I delivery | Preclinical in vitro | Mature vs. neonatal articular bovine chondrocyte culture (carpal joints vs. stifle condyles) | Adenoassociated virus: pAAV/IGF-I transfection vs. exogenous IGF-I stimulation | IGF-I | Dose-dependent increase of IGF-I production after transfection with pAAV/IGF-I; mature chondrocytes respond better than neonate chondrocytes; exogenous delivery into cell culture medium showed lower results |
| Aguilar et al. (48) | Development of new peptide-based material with high affinity to IGF-I | Preclinical in vitro | Neonatal articular bovine chondrocyte culture (stifle condyles) | Hydrogels; alginate (transfection with Fugene 6) | IGF-I | Enhanced binding affinity of IGF-I; extended IGF-I availability; increased GAG and HYPRO synthesis |
| Ko et al. (49) | Evaluate the effects of relaxin expression on fibrosis inhibition in OA synovial fibroblasts | Preclinical in vitro | Human OA synovial fibroblasts | Adenovirus: Ad-RLN | Relaxin | Anti-fibrogenic effects on OA synovial fibroblasts via inhibition collagen synthesis and collagenolytic pathways such as MMP-1,-13, TIMP-1 and -2 |
| Ulrich-Vinther et al. (50) | Investigate potential of TGF-β1 overexpression to restore cartilage anabolism | Preclinical in vitro | Human primary OA chondrocytes | Adenoassociated virus: AAV-TGF-beta1-IRES-eGFP | TGFβ1 | Increased expression of type II collagen, aggrecan; decreased expression of MMP3 |
| Venkatesan et al. (51) | Investigate potential of TGF-β1 overexpression to restructure OA cartilage | Preclinical in vitro and in situ | Human primary OA chondrocytes and OA cartilage explants | Adenoassociated virus: rAAV-hTGF-beta | TGFβ1 | Increased cell proliferation; reduced apoptosis; increased proteoglycan and type-II collagen deposition; decreased type-X collagen content; decreased hypertrophic differentiation players (MMP13, PTHrP and beta-catenin); increased protective TIMP-1 and TIMP-3 expression |
| Noh et al. (52) | Evaluate potential of TGF-β1-secreting human chondrocytes (TG-C) to regenerate cartilage | Preclinical in vivo | Rabbit surgically induced single partial cartilage defect model | Retrovirally induced human chondrocytes | TGFβ1 | Dose-dependent effect on cartilage regeneration |
| Goat surgically induced single full-thickness cartilage defect model | TG-C | Increased proliferation of new chondrocytes; positive effect on joint cartilage at 6 months | ||||
| Lee et al. (53) | Evaluate the effects of TissueGeneC on pain and cartilage structure via the polarization of M2 macrophages | Preclinical in vivo | Rat MIA model | TissueGeneC | TGFβ1 | Pain relief and cartilage structural improvement; increased IL-10 in the synovial fluid; induction of arginase 1 expression (M2 macrophages marker) and decreased CD86 (M1 macrophages marker) → Polarization of M2 macrophages |
| Gao et al. (54) | Compare BMP2 delivery by coacervation and lentiviral delivery on cartilage repair | Preclinical in vitro | hMDSCs | Lentivirally (LBMP2/GFP) transduced hMDSCs; coacervate sustain release technology | BMP-2 | LBMP2/GFP transduction increases chondrogenic differentiation of hMDSCs |
| Preclinical in vivo | Rat MIA model | hMDSC-LBMP2/GFP improves cartilage repair and of cartilage erosion; coacervate delivery of BMP2 similar articular cartilage regeneration than with hMDSC-LBMP2/GFP | ||||
| Matsumoto et al. (55) | Evaluate the effect of BMP-4 and Flt-1-transduced MDSCs on cartilage repair in a rat OA model | Preclinical in vivo | Rat MIA model | Retrovirally transduced MDSCs | BMP-4 •Flt-1 | BMP-4-transduced MDSCs lead to good cartilage repair, but with osteophyte formation; exacerbated effect without osteophyte formation with the combination of sFlt-1 and BMP-4-transduced MDSCs; higher levels of chondrocyte differentiation and proliferation; lower levels of chondrocyte apoptosis |
| Tang et al. (56) | Assess the effect of follistatin delivery on metabolic inflammation and knee OA caused by a high-fat diet | Preclinical in vivo | Mouse DMM model | Adenoassociated virus: AAV9-FST | Follistatin (FST) | Reduced cartilage degeneration; decreased joint synovitis; lower levels of pro-inflammatory cytokines; normalization of obesity-induced increased heat withdrawal latency; enhanced muscle growth and muscle performance; protection from injury-mediated trabecular and cortical bone structure changes |
| Chen et al. (57) | Evaluate the effects of nanomicrosphere-delivered GDF-5 on OA | Preclinical in vitro | Rabbit chondrocytes | Nanomicrospheres | GDF-5 | Increased expression of collagen II and aggrecan |
| Preclinical in vivo | Rabbit ACLT and menisectomy model | Improved cartilage morphology and joint structure |