The synergistic effect of NELL1 and adipose-derived stem cells on promoting bone formation in osteogenesis imperfecta treatment.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and deformity. Mesenchymal stem cells (MSCs) infusion can improve bone performance mainly due to their differentiation into osteoblasts in OI therapy. The osteoinductive activity of NELL1 have benefited various bone defect and osteoporotic models by promoting bone formation. The present study investigated the efficacy of combined use of NELL1 and adipose-derived mesenchymal stem cells (ADSCs) in OI treatment. Methods Lentiviral vector carrying mouse Nell1 gene was constructed and lentivirus were used to infect ADSCs. The osteogenic capacity of MC3T3-E1 and ADSCs stimulated by recombinant mouse NELL1 protein (rmNELL1) and Nell1 gene genetically modified ADSCs (lenti-Nell1-ADSCs) were estimated by real-time quantitative PCR. Thirty adult male OI type I mice with single Col1a1 gene knockout were randomly divided into five groups and received intravenously injected PBS, rmNELL1 (1.25 mg/Kg), ADSCs (2 × 10 5 cells per mice), rmNELL1 (1.25 mg/Kg) combined with ADSCs (2 × 10 5 cells per mice), or lenti-Nell1-ADSCs (2 × 10 5 cells per mice) respectively. Six wildtype (WT) mice served as positive control. Bone formation was examined after 4 weeks using micro-CT, histological and immunohistochemical methods. Results Three osteoblast related genes of MC3T3-E1 and ADSCs were significantly up-

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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