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首页> 外文期刊>Acta biomaterialia >Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix
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Anatomical region-dependent enhancement of 3-dimensional chondrogenic differentiation of human mesenchymal stem cells by soluble meniscus extracellular matrix

机译：通过可溶性弯月面细胞外基质依赖性区域依赖性增强人间充质干细胞的三维软骨菌分化

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Extracellular matrix (ECM) derived from decellularized tissues has been found to promote tissue neogenesis, most likely mediated by specific biochemical and physical signaling motifs that promote tissue specific differentiation of progenitor cells. Decellularized ECM has been suggested to be efficacious for the repair of tissue injuries. However, decellularized meniscus contains a dense collagenous structure, which impedes cell seeding and infiltration and is not readily applicable for meniscus repair. In addition, the meniscus consists of two distinct anatomical regions that differ in vascularity and cellular phenotype. The purpose of this study was to explore the region-specific bioactivity of solubilized ECM derived from the inner and outer meniscal regions as determined in 2D and 3D cultures of adult mesenchymal stem cells (MSCs). When added as a medium supplement to 2D cultures of MSCs, urea-extracted fractions of the inner (imECM) and outer meniscal ECM (omECM) enhanced cell proliferation while imECM most strongly upregulated fibrochondrogenic differentiation on the basis of gene expression profiles. When added to 3D cultures of MSCs seeded in photocrosslinked methacrylated gelatin (GeIMA) hydrogels, both ECM fractions upregulated chondrogenic differentiation as determined by gene expression and protein analyses, as well as elevated sulfated glycosaminoglycan sGAG content, compared to ECM-free controls. The chondrogenic effect at day 21 was most pronounced with imECM supplementation, but equivalent between ECM groups by day 42. Despite increased cartilage matrix, imECM and omECM constructs possessed compressive moduli similar to controls. In conclusion, soluble meniscal ECM may be considered for use as a tissue-specific reagent to enhance chondrogenesis for MSC-based 3D cartilage tissue engineering.
机译：从脱细胞组织来源的细胞外基质（ECM），已经发现，以促进组织新生，最有可能通过促进祖细胞的组织特异性分化特定的生化和物理信号基序介导的。脱细胞ECM已建议是有效的组织损伤的修复。然而，脱细胞的弯月包含致密的胶原结构，阻碍细胞接种和渗透和不容易适用于半月板修复。另外，弯月面是由在血管和细胞表型不同的两个不同的解剖区域。本研究的目的是探讨在成人的2D和3D培养测定间充质干细胞（MSC）从所述内侧和外侧半月板区域衍生的增溶的ECM的区域特异性的生物活性。当作为培养基添加剂加入到MSC的2D培养，外半月板ECM（omECM）内（imECM）的尿素萃取馏分和增强的细胞增殖而imECM最强烈上调的基因表达图谱的基础上fibrochondrogenic分化。当添加到MSC的3D培养接种在光交联的甲基丙烯酸酯化的明胶（GeIMA）水凝胶，二者ECM馏分上调如通过基因表达和蛋白质分析测定软骨细胞分化，以及升高的硫酸化糖胺聚糖的sGAG含量，相对于ECM-自由控制。在第21天的软骨形成效果最为显用imECM补充，而是由42天ECM组之间等效尽管增加软骨基质，imECM和omECM构建体所具有的压缩模量与对照相似。总之，可溶性半月板ECM可被视为用作组织特异性试剂来增强用于基于MSC-3D软骨组织工程软骨。

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