Consistent Osteoblastic Differentiation of Human Mesenchymal Stem Cells with Bone Morphogenetic Protein 4 and Low Serum
Consistent Osteoblastic Differentiation of Human Mesenchymal Stem Cells with Bone Morphogenetic Protein 4 and Low Serum
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DOI：
10.1089/ten.tec.2010.0387
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发表时间：
2011-03-01
影响因子：
3
通讯作者：
Deschaseaux, Frederic
中科院分区：
文献类型：
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作者：
Cordonnier, Thomas;Langonne, Alain;Deschaseaux, Frederic
提供完全成熟且有功能的成骨细胞对于骨组织工程和再生医学来说是一项挑战。这种细胞可以通过不同的成骨因子诱导后从多能骨髓间充质干细胞（MSC）中获得。然而，结果存在一些差异，特别是由于血清的使用和成骨因子的类型。在这项研究中，我们通过评估体外表型和体内功能性成骨细胞，比较了地塞米松（Dex）或骨形态发生蛋白（BMP）诱导的骨髓间充质干细胞的成骨分化。将胎牛血清含量从10%降低至2%显着增加了成骨过程中矿物质沉积和成骨细胞标志物的表达。与 Dex 条件相比，BMP4 的添加极大地提高了 MSC 向完全成熟成骨细胞的分化，如 Osterix 的高表达所示。这些结果在不同的支持基质、塑料瓶或双相磷酸钙生物材料中得到了证实。根据体外结果，与 Dex 衍生的成骨细胞相比，来自 MSC 的 BMP4 衍生的成骨细胞能够在裸鼠皮下组织中显着产生新骨。总之，我们描述了一种方便的离体方法，使用 BMP4 和低血清从人 MSC 中产生一致成熟的功能性成骨细胞。
Providing fully mature and functional osteoblasts is challenging for bone tissue engineering and regenerative medicine. Such cells could be obtained from multipotent bone marrow mesenchymal stem cells (MSCs) after induction by different osteogenic factors. However, there are some discrepancies in results, notably due to the use of sera and to the type of osteogenic factor. In this study, we compared the osteogenic differentiation of bone marrow MSCs induced by dexamethasone (Dex) or bone morphogenetic proteins (BMPs) by assessing phenotypes in vitro and functional osteoblasts in vivo. Reducing the content of fetal calf serum from 10% to 2% significantly increased the mineral deposition and expression of osteoblastic markers during osteogenesis. In comparison to Dex condition, the addition of BMP4 greatly improved the differentiation of MSCs into fully mature osteoblasts as seen by high expression of Osterix. These results were confirmed in different supportive matrixes, plastic flasks, or biphasic calcium phosphate biomaterials. In contrast to Dex-derived osteoblasts, BMP4-derived osteoblasts from MSCs were significantly able to produce new bone in subcutis of nude mice in accordance with in vitro results. In conclusion, we describe a convenient ex vivo method to produce consistently mature functional osteoblasts from human MSCs with use of BMP4 and low serum.