Differential effects of growth factors on tissue-engineered cartilage
Differential effects of growth factors on tissue-engineered cartilage
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DOI：
10.1089/107632702753503072
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发表时间：
2002-02-01
影响因子：
--
通讯作者：
Freed, JE
中科院分区：
文献类型：
--
作者：
Blunk, T;Sieminski, AL;Freed, JE
考察了4种调节因子对组织工程软骨的影响，特别是对细胞外基质(ECM)的主要成分--糖胺多聚糖(GAG)和胶原含量的影响。将牛小牛关节软骨细胞接种到可生物降解的聚乙醇酸(PGA)支架上，在添加或不添加胰岛素样生长因子(IGF-I)、白介素4(IL-4)、转化生长因子-β1(TGF-β1)或血小板衍生生长因子(PDGF)的培养液中进行培养。在4周的培养中，IGF-I、IL-4和TGF-β1使构建湿重增加了1.5-2.9倍，并增加了软骨细胞外基质成分的数量。在以高细胞密度种植的构建物中，IGF-I(10-300 ng/mL)维持GAG的湿重分数，而在以较低细胞密度种植的构建物中，IGF-I的GAG含量最多增加五倍。转化生长因子-β1(30 ng/mL)使湿重的总胶原含量增加1.4倍，同时保持较高的II型胶原含量(占总胶原量的79+/-11%)。IL-4(1-100 ng/mL)可最大限度地减少构建表面GAG缺失区域的厚度。PDGF(1~100 ng/mL)可降低细胞构筑生长速度和细胞外基质含量。因此，不同的调控因子可引起明显不同的软骨形成反应，并可用于选择性地控制工程软骨的生长速度和改善其组成。
The effects of four regulatory factors on tissue-engineered cartilage were examined with specific focus on the ability to increase construct growth rate and concentrations of glycosaminoglycans (GAG) and collagen, the major extracellular matrix (ECM) components. Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid (PGA) scaffolds and cultured in medium with or without supplemental insulin-like growth factor (IGF-I), interleukin-4 (IL-4), transforming growth factor-beta1 (TGF-beta1) or platelet-derived growth factor (PDGF). IGF-I, IL-4, and TGF-beta1 increased construct wet weights by 1.5-2.9-fold over 4 weeks of culture and increased amounts of cartilaginous ECM components. IGF-I (10-300 ng/mL) maintained wet weight fractions of GAG in constructs seeded at high cell density and increased by up to fivefold GAG fractions in constructs seeded at lower cell density. TGF-beta1 (30 ng/mL) increased wet weight fractions of total collagen by up to 1.4-fold while maintaining a high fraction of type II collagen (79 +/- 11% of the total collagen). IL-4 (1-100 ng/mL) minimized the thickness of the GAG-depleted region at the construct surfaces. PDGF (1-100 ng/mL) decreased construct growth rate and ECM fractions. Different regulatory factors thus elicit significantly different chondrogenic responses and can be used to selectively control the growth rate and improve the composition of engineered cartilage.