Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6
Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6
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DOI：
10.1002/art.21779
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发表时间：
2006-04-01
影响因子：
--
通讯作者：
Guilak, F
中科院分区：
文献类型：
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作者：
Estes, BT;Wu, AW;Guilak, F
目标。最近的研究发现，在人皮下脂肪组织中有丰富的多能祖细胞来源，称为人脂肪源性成体干细胞（ADAS细胞）。在特定培养基配方的作用下，包括转化生长因子β 1 (TGF β 1)，这些细胞表现出向软骨细胞样表型分化的显著能力，表达软骨特异性基因和蛋白，如聚集蛋白和11型胶原蛋白。然而，其他生长因子对ADAS细胞成软骨分化的影响尚不完全清楚。本研究旨在探讨TGF β 1、TGF β 3、胰岛素样生长因子1、骨形态发生蛋白6 （BMP-6）和地塞米松在不同组合下对海藻酸珠ADAS细胞成软骨潜能的影响。采用定量聚合酶链反应、3h -脯氨酸和35s -硫酸盐掺入、特异性细胞外基质成分免疫标记等方法检测海藻酸盐包膜ADAS细胞的软骨形成反应。在不同的培养条件下，观察到所有结果的软骨形成有显著差异。最值得注意的是，与对照组相比，BMP-6上调AGC1和COL2A1的表达量平均分别为205倍和38倍，而下调COLIOAI的表达量约为2倍。这些发现表明，BMP-6是ADAS细胞软骨形成的有效诱导剂，而间充质干细胞在BMP-6的作用下表现出X型胶原蛋白的表达增加和肥厚表型。结合含有BMP-6的生长因子可能提供一种调节ADAS细胞分化的新方法，用于组织工程修复或关节软骨再生。
Objective. Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adipose-derived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor beta 1 (TGF beta 1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type 11 collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGF beta 1, TGF beta 3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.Methods. The chondrogenic response of alginate-encapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3 H-proline and 35 S-sulfate incorporation, and immunolabeling for specific extracellular matrix components.Results. Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 upregulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COLIOAI expression by similar to 2-fold.Conclusion. These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.