Variations in the ratios of co-cultured mesenchymal stem cells and chondrocytes regulate the expression of cartilaginous and osseous phenotype in alginate constructs
Variations in the ratios of co-cultured mesenchymal stem cells and chondrocytes regulate the expression of cartilaginous and osseous phenotype in alginate constructs
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共培养的间充质干细胞和软骨细胞比例的变化调节藻酸盐构建体中软骨和骨表型的表达
DOI：
10.1016/j.bone.2008.07.240
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发表时间：
2009-07-01
期刊：
影响因子：
4.1
通讯作者：
Yang, Zhi-ming
中科院分区：
文献类型：
--
作者：
Mo, Xiang-tao;Guo, Shang-chun;Yang, Zhi-ming
由于骨髓间充质干细胞（mesenchymal stem cells，MSCs）具有自我更新和多向分化的能力，本研究旨在探讨人MSCs（human MSCs，hMSCs）与兔关节软骨细胞（rACs）共培养，促进hMSCs向软骨细胞和成骨细胞分化，用于临床骨关节炎治疗的可行性和有效性。将两种不同的细胞类型单独或以三种比例（hMSC与rAC的2：1、1：1、1：2）之一包封在藻酸盐水凝胶中，并在软骨形成条件下培养28天。结果表明，新合成的软骨细胞外基质（ECM）和II型胶原（col-2）基因信号上调与更大的hMSC比例和更长的培养时间。然而，仅在单个hMSC组中发现了针对人的特异性col-2基因探针，而在所有共培养组中均未发现，这表明增强的软骨表型来源于共培养的rAC。第28天仅在2：1组中检测到骨表型;异种骨钙素检测显示其来源于hMSCs。这表明共培养的hMSC和rAC的比例的变化调节软骨和骨表型以及藻酸盐构建体中hMSC的分化。该研究为细胞-细胞相互作用在调节细胞分化和细胞功能方面的作用提供了新的见解，并强调了为组织工程治疗开发适当分化方案的重要性。(C)2009爱思唯尔公司版权所有
As mesenchymal stem cells (MSCs) are capable of self-renewal and multilineage differentiation, the feasibility and efficacy of co-culturing human MSCs (hMSCs) with rabbit articular chondrocytes (rACs) to promote chondrogenic and osteogenic differentiation of hMSCs for clinical osteoarthritic therapy were investigated in the present Study. The two distinct cell types were encapsulated in alginate hydrogels singly or in one of three ratios (2:1, 1:1, 1:2 of hMSCs to rACs) and Cultured under chondrogenic conditions for 28 days. The results demonstrated that newly synthesized cartilaginous extracellular matrix (ECM) and type II collagen (col-2) gene signal were upregulated with greater hMSC ratios and longer culture periods. However, a specific col-2 gene probe for human was found only in single hMSC group but absent in all co-culture groups, which indicate that the enhanced cartilaginous phenotype originated from the co-cultured rACs. Osseous phenotype was histologically detected only in the 2:1 group on day 28; and xenogenic osteocalcin assay showed that it originated from hMSCs. This suggests that variations in the ratios of co-cultured hMSC and rAC regulated the cartilaginous and osseous phenotype as well as the differentiation of hMSCs in alginate constructs. The study provides new insights into the role of cell-cell interactions in regulating both cell differentiation and cell function and highlights the importance of developing appropriate differentiation protocols for tissue engineering therapies. (C) 2009 Elsevier Inc. All rights reserved