Abstract:
The compatibility of bone graft substitutes (BGS) with mesenchymal stem cells (MSCs) is an important parameter to consider for their use in repairing bone defects as it eventually affects the clinical outcome. In the present study, a few commercially available BGS - β-tricalcium phosphate (β-TCP), calcium sulfate, gelatin sponge, and different forms of hydroxyapatite (HAP) were screened for their interactions with MSCs from adipose tissue (ADSCs). It was demonstrated that HAP block favorably supported ADSC viability, morphology, migration, and differentiation compared to other scaffolds. The results strongly suggest the importance of preclinical evaluation of bone scaffolds for their cellular compatibility. Furthermore, the bone regenerative potential of HAP block with ADSCs was evaluated in an ex vivo bone defect model developed using patient derived trabecular bone explants. The explants were cultured for 45 days in vitro and bone formation was assessed by expression of osteogenic genes, ALP secretion, and high resolution computed tomography. Our findings confirmed active bone repair process in ex vivo settings. Addition of ADSCs significantly accelerated the repair process and improved bone microarchitecture. This ex vivo bone defect model can emerge as a viable alternative to animal experimentation and also as a potent tool to evaluate patient specific bone therapeutics under controlled conditions.
摘要:
骨移植替代物(BGS)与间充质干细胞(MSCs)的相容性是其用于修复骨缺损的重要参数,因为它最终会影响临床结果。在本研究中,一些市售的BGS-β-磷酸三钙(β-TCP),硫酸钙,明胶海绵,和不同形式的羟基磷灰石(HAP)筛选它们与来自脂肪组织(ADSC)的MSC的相互作用。事实证明,HAP阻断有利地支持ADSC的生存能力,形态学,迁移,以及与其他支架相比的差异。结果强烈表明,临床前评估骨支架对其细胞相容性的重要性。此外,在使用患者来源的小梁骨外植体建立的离体骨缺损模型中评估了用ADSC阻断HAP的骨再生潜力.将外植体在体外培养45天,并通过成骨基因的表达来评估骨形成。ALP分泌,和高分辨率计算机断层扫描。我们的发现证实了离体环境中活跃的骨修复过程。添加ADSCs可显着加速修复过程并改善骨微结构。这种离体骨缺损模型可以作为动物实验的可行替代方案出现,也可以作为在受控条件下评估患者特异性骨疗法的有效工具。