Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes

Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes
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DOI:
10.1016/j.joca.2006.06.009
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发表时间:
2007-01-01
影响因子:
7
通讯作者:
Martin, I.
Martin, I.
中科院分区:
医学2区
文献类型:
--
作者:
Marsano, A.;Millward-Sadler, S. J.;Martin, I.

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目的:为了确定一个合适的细胞来源,以产生半月板替代品,其中将可通过关节镜检查受伤的膝关节。方法:分别在有或无特异性生长因子的条件下扩增人内半月板细胞、脂肪垫细胞、滑膜细胞和关节软骨细胞(转化生长因子-β 1,成纤维细胞生长因子-2和Platelet衍生的生长因子bb,TFP),然后在沉淀培养物中诱导形成三维软骨组织,或使用基于透明质酸的支架(Hyaff(R)-11),在培养物中或在裸鼠中。结果:TFP扩增后,所有细胞类型的糖胺聚糖(GAG)沉积增加4.1倍,FPC和SMC的II型胶原mRNA表达增加472倍。在所有模型中,AC生成的组织含有最高比例的GAG(高达湿重的1.9%),并且II型胶原蛋白(半月板内部无血管区域特异性)、IV型胶原蛋白(主要存在于半月板的外部血管化区域)以及I、III和VI型胶原蛋白(两个半月板区域共有)染色呈阳性。相反,内半月板、FPC和SMC形成的组织含有可忽略的GAG,且未检测到II型胶原蛋白。AC产生的组织仍然是生化和表型稳定的异位implantation.Conclusions:在我们的实验条件下,只有AC产生的组织含有相关量的GAG和细胞表型与那些内部和外部半月板区域兼容。相反,其他研究的细胞来源形成的组织类似于半月板的外部区域。基于AC的移植物是否能够达到半月板组织典型的复杂结构和功能组织仍有待确定。(C)2006年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints.Methods: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-betal, Fibroblast growth factor-2 and Plate let-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff(R)-11), in culture or in nude mice. Human native menisci were assessed as reference.Results: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9% of wet weight) and were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation.Conclusions: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.