Table 4.
Applications of genetically modified MSCs in vivo.
| Delivery System | Carrier | Nucleic Acid | Cell Vehicles | Application | Model/Host | Ref | ||
|---|---|---|---|---|---|---|---|---|
| Type | Composition | Vector | Delivered Gene/siRNA | |||||
| Non-viral | Liposomes | Lipofectamine Plus® | Plasmid DNA | hTERT | MSC line derived from fetal porcine pancreas | Hyperglycemia | Diabetic model/Kunbai strain mice | [113] |
| Polymer | PEI | Plasmid DNA | TRAIL | BM-MSCs | Melanoma | Melanoma model/e C57BL/6 mice | [115] | |
| Polymer | Chitosan | Plasmid DNA | BMP-2 | BM-MSCs | Bone regeneration | Calvarial defect model/Rats | [85] | |
| Polymer | PEI | Plasmid DNA | BMP-2 | BM-MSCs deriver MVs within gene-activated scaffold (DBM/MVs-PEI/phBMP2) | Bone regeneration | Femoral condylar defect/New Zealand white rabbits | [86] | |
| Polymer | Alginate GAM | Plasmid DNA | BMP-2 | Rat BM-MSCs | Bone regeneration | Orthotopic spinous process defect/Fischer 344 inbred rats | [87] | |
| Polymer | LPEI | Plasmid DNA | VEGF | BM-MSCs | Myocardial infarction | MI model/SD rats | [95] | |
| Polymer | Cationized pullulan | Plasmid DNA | Suicide gene (CMV-TK) | Rat BM-MSCs | Melanoma | Pulmonary melanoma metastasis model/C57BL6 mice | [83] | |
| Polymer | LPEI | Plasmid DNA | CDY::UPRT | AT-MSCs | GDEPT: Chemo-resistant glioblastoma | Temozolomide resistant U-251MG cells/Nude mice | [116] | |
| Polymers | PEI-PLGA | Plasmid DNA and siRNA | coSOX9-pDNA/Cbfa-1-siRNA | hMSCs encapsulated in fibrin hydrogels | Chondrogenic differentiation | Nude BALB/c mice | [117] | |
| Polymers | PLL-PEI | Plasmid DNA | HSV-TK and TRAIL | rMSCs | Glioblastoma | Glioma model/SD rats | [101] | |
| Polymeric NPs | BA-PEI | Plasmid DNA | VEGF | BM-MSCs | Myocardial infarction | MI model/SD rats | [96] | |
| Plasmid-activated scaffolds | Chitosan-gelatin andnHA | Plasmid DNA | TGF-β1 and BMP-2 | BM-MSCs | Regeneration of articular cartilage and subchondral bone | Knee ostochondral defect model/Rabbits | [118] | |
| nHA dual gene-activated scaffold | nHA and PEI | Plasmid DNA | BMP-2 and VEGF | rMSCs | Bone regeneration | Critical-sized cranial bone defect model/Rats | [88] | |
| Peptide conjugated NPs | Cationic AuNPs and PEP | Plasmid DNA | VEGF | Rat BM-MSCs | Antimicrobial and wound healing properties | Infected full thickness skin defect model/Mice | [114] | |
| Viral | AAV | IL-10 | hBM-MSCs | Cerebral ischemia | MCAO I/R model/SD rats | [82] | ||
| Adenovirus | HSV-TK/GCV | BM-MSCs | Intracranial gliomas | Intracranial human U87 glioma model/Nude mice | [100] | |||
| Adenovirus | HGF | hBM-MSCs | Spinal cord injury | Spinal cord injury model/ SD rats | [80] | |||
| Adenovirus | EGFR | Murine BM-MSCs | Brain tumors | Intracranial GL261 glioma or B16 melanoma/C57BL/6 mice | [119] | |||
| Adenovirus | IFN-β | hBM-MSCs | Pancreatic cancer | Transplant PANC-1 cancer model/SCID mice | [103] | |||
| Fiber-modified adenovirus | kringle1-5/EGFP | hPMSCs in Matrigel plugs | Suppression of angiogenesis | Subcutaneous cell loaded matrigel plugs/ BALB/c nude | [105] | |||
| Gamma -Retrovirus | IL7-IL12 | hBM-MSCs | Colorectal cancer | Transplant LS174T colorectal cancer model/NSG mice | [102] | |||
| Gamma-retrovirus | HSV-TK | hBM-MSCs | Gastrointestinal/ hepatopancreatobiliary adenocarcinoma | Phase I and II clinical trial | [84] | |||
| HSV-1 | HGF | rBM-MSCs | Cerebral ischemia | MCAO I/R model/Wistar rats | [81] | |||
| Lentivirus | miR-126 | BM-MSCs | Myocardial infarction | MI model/Mice | [99] | |||
| Lentivirus | HGF | UCB-MSCs | Myocardial infarction | MI model/SCID mice | [97] | |||
| Lentivirus | FGF21 | Mouse BM-MSCs | Brain Injury | Impact-induced traumatic brain Injury model/C57BL/6 mice | [92] | |||
| Lentivirus | CXCR4 | rBM-MSCs | Cerebral ischemia | MCAO I/R model/SD rats | [94] | |||
| Recombinant adenovirus | VEGF | BM-MSCs | Cerebral ischemia | MCAO I/R model/rats | [93] | |||
| Retrovirus | AKT | Mouse BM-MSCs | Myocardial infarction | MI model/C57BL/6 mice | [98] | |||
| Hybrid | Adenovirus/liposome | Ad-hEndo | hPMSCs | Ovarian cancer | Transplant A2780 ovarian cancer model/ Nude mice | [104] | ||
| Adenovirus/CPP | stTRAIL | hUCB-MSCs | Glioblastoma | Intracranial xenograft human glioma model/Athymic nude mice | [120] | |||
| Adenovirus/4HP4 | IL-12M | rBM-MSCs | Melanoma and cervical cancer | B16F10 melanoma and TC-1 cervical cancer models/SCID mice | [121] | |||
Note: 4HP4: tetrameric form of cell-permeable peptide; CPP: cell-permeable peptide; HSV: herpes simplex virus; tTATop-BMP-2: tetracycline transactivator and BMP-2 cDNAs; BA-PEI: bile acid-modified polyethyleneimine; PMAA: polymethacrylate acid; CMV: cytomegalovirus; AT-MSCs: adipose tissue-derived MSCs; HIF-1 α: hypoxia-inducible factor-1α; CDY::UPRT: cytosine deaminase and uracil phosphoribosyl transferase; GAM: gene-activated matrix; GDEPT: gene-directed enzyme prodrug therapy; MVs: microvesicles; DBM: demineralized bone matrix; PLL-PEI: polylysine-modified polyethylenimine; hPMSCs: human placenta-derived MSCs; HSV: herpes simplex virus; MCAO I/R: middle cerebral artery occlusion ischemia/reperfusion; SD: Sprague-Dawley; MI: myocardial infarction; hEndo: human endostatin; UCB-MSCs: umbilical cord blood-derived MSCs.