Human mesenchymal stem cells tissue development in 3D PET matrices
Human mesenchymal stem cells tissue development in 3D PET matrices
复制标题
DOI：
10.1021/bp034296z
复制
发表时间：
2004-05-01
影响因子：
2.9
通讯作者：
Bunnell, B
中科院分区：
文献类型：
--
作者：
Grayson, WL;Ma, T;Bunnell, B
人类间充质干细胞（hMSCs）是具有广泛治疗潜力的工程组织构建体的有吸引力的细胞来源。研究了在非织造聚对苯二甲酸乙二醇酯（PET）纤维基质中的三维（3D）hMSC组织发育。将HMSCs接种到三维PET支架上并培养超过1个月。它们的增殖率受接种密度的影响，但仍远低于2D对照。与2D表面相比，在3D支架中生长的hMSCs分泌并嵌入由胶原蛋白I、胶原蛋白IV、纤连蛋白和层粘连蛋白组成的广泛ECM网络中。HMSC受到相邻PET纤维方向的影响，将ECM蛋白组织成高度对齐的原纤维。我们观察到与2D培养相比，3D培养中α（2）β（1）整联蛋白的表达增加，但α（5）β（1）整联蛋白的表达略有下降，并发现α（v）β（3）仅在2D中表达。桩蛋白的表达下调，在三维文化与伴随的变化，其定位模式。我们通过将支架中生长的细胞分化成骨细胞和脂肪细胞，证明了3D组织构建物的多谱系潜力。总之，这些结果表明，在三维支架中生长的hMSCs显示出与其二维对应物不同的组织发育模式，并为设计用于开发组织工程构建体的三维支架提供了重要线索。
Human mesenchymal stem cells (hMSCs) are attractive cell sources for engineered tissue constructs with broad therapeutic potential. Three-dimensional (3D) hMSC tissue development in nonwoven poly(ethylene terephthalate) (PET) fibrous matrices was investigated. HMSCs were seeded onto 3D PET scaffolds and were cultured for over 1 month. Their proliferation rates were affected by seeding density but remained much lower than those of 2D controls. Compared to 2D surfaces, hMSCs grown in 3D scaffolds secreted and embedded themselves in an extensive ECM network composed of collagen I, collagen IV, fibronectin, and laminin. HMSCs were influenced by the orientation of adjacent PET fibers to organize the ECM proteins into highly aligned fibrils. We observed the increased expressions of alpha(2)beta(1) integrin but a slight decrease in the expression Of alpha(5)beta(1) integrin in 3D compared to 2D culture and found that alpha(v)beta(3) was expressed only in 2D. Paxillin expression was down-regulated in 3D culture with a concomitant change in its localization patterns. We demonstrated the multi-lineage potentials of the 3D tissue constructs by differentiating the cells grown in the scaffolds into osteoblasts and adipocytes. Taken together, these results showed that hMSCs grown in 3D scaffolds display tissue development patterns distinct from their 2D counterparts and provide important clues for designing 3D scaffolds for developing tissue engineered constructs.