The synergistic osteogenic effects of FGF1 and BMP2 gene modified bone marrow mesenchymal stem cells in spinal fusion

Background Spinal fusion is essential for treating spinal disorders, but achieving robust bone formation remains challenging. This study evaluated whether FGF1 and BMP2 co-expression in gene-modified BMSCs enhances spinal fusion compared to single-gene approaches. Methods BMSCs were transduced with lentiviruses carrying FGF1, BMP2, or both. Osteogenic differentiation, proliferation, and gene expression were assessed in vitro using staining assays, qPCR, Western blotting, CCK-8, ALP tests, and RNA-seq. In vivo studies in rats evaluated local and systemic protein levels, biosafety, and fusion outcomes via micro-CT, histology, immunohistochemistry, and manual palpation. Results Dual-modified BMSCs showed significantly higher transgene expression, proliferation, and ALP activity than single-gene or control groups (p < 0.05). RNA-seq revealed upregulated proliferation, angiogenesis, and osteogenic genes, alongside suppressed inflammatory genes, with PI3K-Akt and MAPK pathway enrichment. High local expression occurred without systemic elevation, and no organ abnormalities were observed. Micro-CT and histology demonstrated the most extensive new bone formation in the dual-gene group. Manual palpation confirmed an 80% fusion rate for LV-FGF1-BMP2 versus 20% (LV-BMP2), 0% (LV-FGF1), and 0% (LV-Vector). Conclusion Dual-gene modification with FGF1 and BMP2 markedly enhances osteogenesis and spinal fusion while maintaining a certain degree of biosafety, representing a promising therapeutic advance over single-gene approaches.