Work

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

Year: 2026

Type: article

Abstract: 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.

Source: Frontiers in Cell and Developmental Biology

DOI: 10.3389/fcell.2026.1971609