Chondrogenic Differentiation of Adipose-Derived Adult Stem Cells by a Porous Scaffold Derived from Native Articular Cartilage Extracellular Matrix
Chondrogenic Differentiation of Adipose-Derived Adult Stem Cells by a Porous Scaffold Derived from Native Articular Cartilage Extracellular Matrix
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DOI：
10.1089/ten.tea.2008.0253
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发表时间：
2009-02-01
影响因子：
4.1
通讯作者：
Guilak, Farshid
中科院分区：
文献类型：
--
作者：
Cheng, Nai-Chen;Estes, Bradley T.;Guilak, Farshid
脂肪来源的成体干细胞（ASC）具有响应特定环境信号（例如生长因子或人工生物材料支架）而分化成软骨形成表型的能力。在这项研究中，我们研究了一个假设，即一个多孔支架完全来自关节软骨可以诱导软骨细胞。将人ASCs接种在来源于成年猪关节软骨的多孔支架上，并在不含外源性生长因子的标准培养基中培养。软骨特异性细胞外基质（ECM）基因的定量RT-PCR分析表明，在支架内接种的ASCs的软骨发生是明显的。组织学和免疫组织化学检查显示，软骨特异性ECM成分，特别是II型胶原蛋白，丰富的生产后4或6周的文化。培养6周后，ASC接种构建体中的细胞形态与天然关节软骨组织中的细胞形态相似，圆形细胞位于支架的富含糖胺聚糖的区域。双相机械测试表明，ASC接种结构的聚集体模量随时间推移而增加，到第42天达到150 kPa，比未接种对照高出三倍以上。这些结果表明，来源于关节软骨的多孔支架具有诱导ASCs软骨分化的能力，而无需外源性生长因子，ECM大分子的显著合成和积累，以及接近天然软骨的机械性能的发展。这些发现支持了加工软骨ECM作为软骨组织工程生物材料支架的潜力。为了充分认识这些观察结果的临床意义，有必要进行额外的体内评价。
Adipose-derived adult stem cells (ASCs) have the ability to differentiate into a chondrogenic phenotype in response to specific environmental signals such as growth factors or artificial biomaterial scaffolds. In this study, we examined the hypothesis that a porous scaffold derived exclusively from articular cartilage can induce chondrogenesis of ASCs. Human ASCs were seeded on porous scaffolds derived from adult porcine articular cartilage and cultured in standard medium without exogenous growth factors. Chondrogenesis of ASCs seeded within the scaffold was evident by quantitative RT-PCR analysis for cartilage-specific extracellular matrix (ECM) genes. Histological and immunohistochemical examination showed abundant production of cartilage-specific ECM components-particularly, type II collagen-after 4 or 6 weeks of culture. After 6 weeks of culture, the cellular morphology in the ASC-seeded constructs resembled those in native articular cartilage tissue, with rounded cells residing in the glycosaminoglycan-rich regions of the scaffolds. Biphasic mechanical testing showed that the aggregate modulus of the ASC-seeded constructs increased over time, reaching 150 kPa by day 42, more than threefold higher than that of the unseeded controls. These results suggest that a porous scaffold derived from articular cartilage has the ability to induce chondrogenic differentiation of ASCs without exogenous growth factors, with significant synthesis and accumulation of ECM macromolecules, and the development of mechanical properties approaching those of native cartilage. These findings support the potential for a processed cartilage ECM as a biomaterial scaffold for cartilage tissue engineering. Additional in vivo evaluation is necessary to fully recognize the clinical implication of these observations.