Potier Esther, Ferreira Elisabeth, Andriamanalijaona Rina, Pujol Jean-Pierre, Oudina Karim, Logeart-Avramoglou Delphine, Petite Hervé
Laboratoire de Recherches Orthopédiques (B2OA), UMR CNRS 7052, Faculté de Médecine Lariboisière-Saint-Louis, 10 Avenue de Verdun, 75010 Paris, France.
Bone. 2007 Apr;40(4):1078-87. doi: 10.1016/j.bone.2006.11.024. Epub 2007 Feb 2.
Mesenchymal stromal cells (MSCs) seeded onto biocompatible scaffolds have been proposed for repairing bone defects. When transplanted in vivo, MSCs (expanded in vitro in 21% O(2)) undergo temporary oxygen deprivation due to the lack of pre-existing blood vessels within these scaffolds. In the present study, the effects of temporary (48 h) exposure to hypoxia (<or=1% O(2)) on primary human MSC survival and osteogenic potential were investigated. Temporary exposure of MSCs to hypoxia had no effect on MSC survival, but resulted in (i) persistent (up to 14 days post exposure) down-regulation of cbfa-1/Runx2, osteocalcin and type I collagen and (ii) permanent (up to 28 days post exposure) up-regulation of osteopontin mRNA expressions. Since angiogenesis is known to contribute crucially to alleviating hypoxia, the effects of temporary hypoxia on angiogenic factor expression by MSCs were also assessed. Temporary hypoxia led to a 2-fold increase in VEGF expression at both the mRNA and protein levels. Other growth factors and cytokines secreted by MSCs under control conditions (namely bFGF, TGFbeta1 and IL-8) were not affected by temporary exposure to hypoxia. All in all, these results indicate that temporary exposure of MSCs to hypoxia leads to limited stimulation of angiogenic factor secretion but to persistent down-regulation of several osteoblastic markers, which suggests that exposure of MSCs transplanted in vivo to hypoxia may affect their bone forming potential. These findings prompt for the development of appropriate cell culture or in vivo transplantation conditions preserving the full osteogenic potential of MSCs.
已提出将接种到生物相容性支架上的间充质基质细胞（MSC）用于修复骨缺损。当在体内移植时，由于这些支架内缺乏预先存在的血管，MSC（在体外21%氧气环境中扩增）会经历暂时的缺氧。在本研究中，研究了短暂（48小时）暴露于低氧（≤1%氧气）对原代人MSC存活和骨生成潜力的影响。MSC短暂暴露于低氧对其存活没有影响，但导致（i）cbfa-1/Runx2、骨钙素和I型胶原持续（暴露后长达14天）下调，以及（ii）骨桥蛋白mRNA表达永久（暴露后长达28天）上调。由于已知血管生成对缓解缺氧至关重要，因此还评估了短暂低氧对MSC血管生成因子表达的影响。短暂低氧导致VEGF在mRNA和蛋白质水平上表达增加2倍。在对照条件下由MSC分泌的其他生长因子和细胞因子（即碱性成纤维细胞生长因子、转化生长因子β1和白细胞介素-8）不受短暂低氧暴露的影响。总而言之，这些结果表明，MSC短暂暴露于低氧会导致血管生成因子分泌受到有限刺激，但会导致几种成骨细胞标志物持续下调，这表明体内移植的MSC暴露于低氧可能会影响其骨形成潜力。这些发现促使人们开发适当的细胞培养或体内移植条件，以保留MSC的全部骨生成潜力。
