BMP7‑overexpressing bone marrow‑derived mesenchymal stem cells (BMSCs) are more effective than wild‑type BMSCs in healing fractures

Abstract

Abstract. Bone fractures are a worldwide public health concern. Previous studies have demonstrated that bone morphogenetic protein-7 (BMP7) gene transfer or mesenchymal stem cells (MSCs) transplantation may be a promising novel therapeutic approach. Therefore, the aim of the present study was to observe the effect of bone BMP7 transfer to MSCs on fracture healing. Bone marrow-derived MSCs (BMSCs) from New Zealand white rabbits were isolated and identified using flow cytometry. A recombinant BMP7 overexpressing adenovirus vector (Adv) was constructed and transfected into BMSCs. The expression of BMP7 was detected by reverse transcription-polymerase chain reaction, immunofluorescence and western blotting. The present study additionally investigated the effect of BMP7 on the differentiation capacity of BMSCs. Finally, tissue-engineered bone was created with support material to verify the effect of BMP7-BMSCs on fracture healing. The results demonstrated that the expression of BMP7 was increased at the mRNA and protein levels in BMSCs following transfection with BMP7 overexpressing Adv. The results additionally demonstrated that the expression of BMP7 enhanced the differentiation capacity of bone marrow mesenchymal stem cells and had a promotional effect on fracture healing. Overall, these data suggest that Adv-BMP7 is useful for introducing foreign genes into BMSCs and will be a powerful gene therapy tool for bone regeneration and other tissue engineering applications in the future.

Differences in the biological properties of mesenchymal stromal cells from traumatic temporomandibular joint fibrous and bony ankylosis: a comparative study

“…For example, the vascular endothelial growth factor (VEGF), as a crucial angiogenic and bone regeneration factor, was confirmed to promote MSCs differentiation towards osteoblast (Murakami et al 2017 ). Bone morphogenetic protein 7 (BMP7), which plays important roles in promoting bone formation and bone fracture healing, was verified to enhance the osteogenic and chondrogenic differentiations of MSCs (Yan et al 2018 ; Peng et al 2019 ). In our previous studies that used the same sheep model, higher mRNA expression levels of VEGF and BMP7 were found in bony ankylosis than in fibrous ankylosis (Yan et al 2014a ; Liang et al 2019 ).…”

Bone morphogenetic protein‑7 upregulates genes associated with osteoblast differentiation, including collagen I, Sp7 and IBSP in gingiva‑derived stem cells

“…BMP-7 expressing stem-cell sheets were applied in the previous studies (20–22). In a previous report, BMP-7 overexpressing adenovirus vector was used to transfect mesenchymal stem cells (22). In a non-union fracture model, BMP-7 expressing mesenchymal stem cells enhanced bone regeneration (20).…”

Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine

“…Biomaterials may be engineered either to act as scaffolds for genetically modified cells or to behave as a guiding system for optimized viral gene transfer, providing in both cases a supportive environment for improved tissue repair sites of cartilage injury [114][115][116][117][118][119], bone defects [120][121][122][123][124][125][126][127][128][129][130][131][132], and tendon/ligament lesions [133,134]. Specifically, MSCs (bone marrow, periosteum, adipose tissue) [114, 115, 117-120, 122-126, 128-133], articular chondrocytes [116], tenocytes [134], muscle cells [120,121], and fibroblasts (skin) [127] have been first transduced with adenoviral [117,119,122,124,[126][127][128][129][130][132][133][134], retro/lentiviral [114,115,120,121,[123][124]…”

“…Specifically, MSCs (bone marrow, periosteum, adipose tissue) [114, 115, 117-120, 122-126, 128-133], articular chondrocytes [116], tenocytes [134], muscle cells [120,121], and fibroblasts (skin) [127] have been first transduced with adenoviral [117,119,122,124,[126][127][128][129][130][132][133][134], retro/lentiviral [114,115,120,121,[123][124][125]131], and rAAV vectors [116,118] to overexpress BMPs (BMP-2, -4, -7, -12) [114, 115, 120-124, 127, 130-132, 134], TGF-b [119,130], FGF-2 [116], VEGF [128], stromal cell-derived factor 1 (SDF-1) [129], connective tissue growth factor (CTGF) [134], SOX9 [117], the runt-related transcription factor 2 (Runx2/ Cbfa1) [125,126], Mohawk homeobox (MKX) transcription factor [133], chondromodulin 1 (Chm-1) [118], and sonic Hedgehog (SHH) [115]. Genetically modified cells were next seeded in scaffolds based on polyglycolic acid (PGA) [114,115,117...…”