Human mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSC^HS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency.

人间充质干细胞（hMSC）治疗为骨软骨再生提供了巨大潜力。此类应用需要在通常补充有成纤维细胞生长因子2（FGF2）的培养基中进行离体扩增。特定的硫酸乙酰肝素（HS）馏分可稳定FGF2-FGF受体复合物。我们表明，FGF2结合HS变体（HS8）加速了新鲜分离的骨髓hMSCs的扩展，而没有损害其幼稚性。重要的是，补充HS8的hMSC（MSC ^HS8）处理后，大鼠和猪的骨软骨缺损的修复均得到改善），通过组织学，生物力学或MRI进行评估。因此，用靶向内源产生的FGF2的HS变体补充hMSC培养基可以消除可能不利地影响其治疗效力的外源生长因子。