Table 2.
Non-viral gene-delivery based therapeutic approaches for bone and/or cartilage repair
| (Therapeutic NA) | Non-viral vector | In vitro / in vivo study | Approach | Methods | Ref |
|---|---|---|---|---|---|
| pDNA (BMP-2) | PEI polyplexes | In vitro (BMMSCs)/ In vivo (rabbit model) | Bone regeneration | Histological, IHC, and immunofluorescence analyses | [5] |
| pDNA (BMP-2 and FGF-2) | PEI polyplexes | In vitro (DPMSCs)/ Ex vivo (tooth model) | Bone regeneration | ELISA, PCR, and ICC analyses | [202] |
| pDNA (BMP-2) | nHA | In vitro BMMSCs)/ In vivo (mice model) | Bone regeneration | ELISA, histological and IHC analyses | [23] |
| pDNA (BMP-2) | nHA | In vitro (BMMSCs)/ In vivo (rat model) | Bone regeneration | ELISA, histological and IHC analyses | [22] |
| pDNA (BMP-2, and VEGF) | GET peptide complexes | In vitro (rMSCs) / In vivo (rat model) | Bone regeneration | ELISA, and histological analyses | [178] |
| pDNA (BMP-2) | TransIT® lipopolyplexes | In vitro (BMMSCs)/ In vivo (rat model) | Bone regeneration | ELISA, histological and IHC analyses | [21] |
| pDNA (BMP-2) | Poly (amido amine) polyplexes | In vitro (TDMSCs)/ In vivo (mice model) | Bone regeneration | PCR, WB, histological and IHC analyses | [20] |
| pDNA (BMP-2/6 and BMP-2/7) | Nucleofector® | In vitro (gMSCs)/ In vivo (mice model) | Bone regeneration | ELISA, and histological analysis | [65] |
| pDNA (BMP-2 and VEGF) | PEI polyplexes and nHA | In vitro (rMSCs) / In vivo (rat model) | Bone regeneration | ELISA, and histological analysis | [69] |
| pDNA (PDGF B) | PEI polyplexes | In vitro (BMMSCs)/ In vivo (rat model) | Bone regeneration | Histological and IHC analyses | [176] |
| pDNA (TGF-β1) | Peptide complexes | In vitro (BMMSCs)/ In vivo (rabbit model) | Bone regeneration | ALP assay, PCR, and histological analysis | [18] |
| pDNA (BMP-2) | PEI polyplexes | In vitro (BMMSCs) | Bone regeneration | PCR, and CC analysis | [177] |
| pDNA (BMP-2) | nHA (mineral coated) | In vitro (hMSCs) | Bone regeneration | ELISA, and CC analysis | [190] |
| pDNA (BMP-2/9) | PEI polyplexes | In vitro (BMMSCs) / In vivo (rat model) | Bone regeneration | PCR, histological analysis, and atomic absorption spectroscopy | [218] |
| PDNA/ (BMP-2 modified) | Peqfect® peptide complexes | In vitro (rAMSCs) | Bone regeneration | ALP assay, ELISA, PCR, and CC analysis | [203] |
| pDNA (TGF-β1) | Stearate cationic peptide complexes | In vitro (MSCs) | Bone regeneration | ALP assay | [189] |
| pDNA (OSX-GFP) | bPEI polyplexes | In vitro (hBMMSCs) | Bone regeneration | CC analysis | [174] |
| pDNA (ephrinB2) | bPEI polyplexes | In vitro (hBMMSCs) | Bone regeneration | PCR, Calcium Liquicolor kit, and blocking peptide assay | [152] |
| pDNA (BMP-2) | nHA and Lipofectamine 2000® | In vitro (rMSCs) | Bone regeneration | Calcium Liquicolor kit, CC and immunofluorescence analyses | [175] |
| cDNA (BMP-2) | Lipofectamine 2000® lipoplexes | In vitro (BMMSCs)/ In vivo (mice model) | Bone regeneration | ELISA, and histological analysis | [115] |
| miRNA (miR-133a) | nHA | In vitro (rMSCs)/ In vivo (rat model) | Bone regeneration | PCR, histological and IHC analyses | [206] |
| miRNA (miR-122) | Commercial transfection reagents (not specified) | In vitro (rMSCs)/ In vivo (rat model) | Bone regeneration | PCR, WB, histological and IHC analyses | [180] |
| miRNA (antmiR-138) | Lipofectamine 2000® | In vitro (BMMSCs)/ In vivo (mice model) | Bone regeneration | PCR, WB, histological and IHC analyses | [117] |
| miRNA (antmiR-138) | Lipofectamine 2000® | In vitro (rat BMMSCs) | Bone regeneration | ALP assay, PCR, and CC analysis | [116] |
| siRNA (siNoggin) | Lipofectamine 2000® and cationic stereosomes | In vitro (AMSCs)/ In vivo (mouse model) | Bone regeneration | ALP assay, PCR, and histological analysis | [118] |
| pDNA (RUNX2); siRNA (siOCT3, siOCT4 and siNANOG) | Poly (β-amino ester) polyplexes | In vitro (DPPSCs) | Bone regeneration | ALP assay, PCR, and ICC analysis | [26] |
| pDNA (BMP-2); siRNA (siNoggin) | C32-122 polyplexes and NA114 lipoplexes | In vitro (BMMSCs) | Bone regeneration | ALP assay, ELISA, PCR, Calcium Reagent kit, and CC analysis | [34] |
| siRNA (siNoggin); miRNA (miR-20a) | PEI polyplexes | In vitro (hMSCs) | Bone regeneration | CC analysis | [68] |
| siRNA (siNoggin); miRNA (miR-20a) | PEI polyplexes | In vitro (hMSCs) | Bone regeneration | ALP assay, PCR, Calcium Reagent kit, and CC analysis | [191] |
| pDNA (BMP-2 and TGF-β3) | nHA and PEI | In vitro (MSCs) | Osteochondral regeneration | ELISA, biochemical, histological and ICC analyses | [19] |
| pDNA (TGF-β1) | Gelatin microspheres | In vitro (hMSCs) | Chondrogenic differentiation | Biochemical, histological and ICC analyses | [1] |
| pDNA (TGF-β1) | Pullulan spermine polyplexes | In vitro (rMSCs) | Chondrogenic differentiation | CC analysis | [135] |
| pDNA (SOX9) | PEI-modified PLGA polyplexes | In vitro (hMSCs) | Chondrogenic differentiation | PCR, biochemical analysis, and immunoblotting | [27] |
| pDNA (Endostatin) | GP2® lipoplexes | In vitro (cBMMSCs) | Chondrogenic differentiation | ELISA, and CC analysis | [188] |
| mRNA (SOX9 and MYOD) | 3DFectIN® lipoplexes | In vitro (hMSCs) | Chondrogenic and myogenic differentiation | PCR, and ICC analysis | [194] |
| pDNA (BMP-2 and TFG-β3) | Lipofectamine 2000® lipoplexes | In vitro (hiPSCs)/ In vivo (rat model) | Osteochondral regeneration | PCR, histological and immunochemical analysis | [111] |
| pDNA (EGFP-C1) | PAA-BA and PEI polyplexes; Lipofectamine 2000® lipoplexes | In vitro (BMMSCs) | Multipotent differentiation | PCR, and ICC analysis | [120] |
| pDNA (BMP-2 and TGF-β3) | PEI polyplexes, HA nanoparticles, RALA peptide | In vitro (hMSCs) | Osteochondral differentiation | ELISA, PCR, biochemical, CC and ICC analyses | [179] |
| pDNA (BMP-2 and TGF-β1) | nHA (mineral-coated) and Lipofectamine 2000® lipoplexes | In vitro (hMSCs) | Osteogenic differentiation | Biochemical and CC analyses | [114] |
| pDNA (BMP-2 and TGF-β3) | CaP nanoparticles or CaP/PEI polyplexes | In vitro (hMSCs) | Osteogenic differentiation | PCR, and CC analysis | [153] |
| pDNA (BMP-2 and TGF-β1) | Scaffold HA | In vivo (rabbit model) | Osteogenic differentiation | Histological analysis | [186] |
| miRNA (miR100-5p and miR143-3P) | PEI polyplexes | In vitro (MSCs) | Osteogenic differentiation | PCR, and CC analysis | [67] |
| miRNA (miR-133a) | nHA | In vitro (hMSCs) | Osteogenic differentiation | PCR, Calcium Liquicolor kit, and ICC analysis | [183] |
| miRNA (antmiR-138) | Chitosan/tripolyphosphate/HA nanoparticles | In vitro (MSCs) | Osteogenic differentiation | PCR, WB, and CC analysis | [184] |
| miRNA (miR-218) | bPEI polyplexes | In vitro (hMSCs) | Osteogenic differentiation | ALP assay, PCR, WB, and CC analysis | [182] |
Abbreviations. pDNA plasmid DNA, BMP-2, -6, -7, -9 bone morphogenic protein-2, -6, -7, -9, PEI polyethyleneimine, BMMSCs bone marrow derived mesenchymal stem cells, FGF-2 fibroblast growth factor, CC cytochemical, DPMSCs dental pulp mesenchymal stem cells, nHA hydroxyapatite nanoparticles, ELISA enzyme-linked immunosorbent assay, PCR polymerase chain reaction, VEGF vascular endothelial growth factor, rMSCs rat mesenchymal stem cells, GET GAG-binding enhanced transduction, TDMSCs tonsil derived mesenchymal stem cells, gMSCs goat mesenchymal stem cells, TGF-β1 and -β3 transforming growth factor-β1 and -β3, ALP alkaline phosphatase, rAMSCs rat adipose derived mesenchymal stem cells, OSX osterix, GFP green fluorescent protein, bPEI branched polyethyleneimine, cDNA circular DNA, miRNA micro-RNA, siRNA small interfering RNA, RUNX2 core binding factor alpha 2, OCT3 and 4 octamer-binding transcription factor 3 and 4, DPPSCs dental pulp pluripotent stem cells, hMSCs human mesenchymal stem cells, SOX9 sex-determining region Y-type high mobility group box 9, cBMMSCs caprine bone marrow derived mesenchymal stem cells, hiPSCs human induced pluripotent stem cells, MYOD myogenic differentiation protein, EGFP enhanced green fluorescent protein, CaP calcium phosphate, HA hyaluronic acid, PAA-BA poly (amidoamine) with pendant aminobutyl group