Mwale Fackson, Girard-Lauriault Pierre-Luc, Wang Hong Tian, Lerouge Sophie, Antoniou John, Wertheimer Michael R
Division of Orthopaedic Surgery, McGill University, Montréal, Québec, Canada.
Tissue Eng. 2006 Sep;12(9):2639-47. doi: 10.1089/ten.2006.12.2639.
Mesenchymal stem cells (MSCs) are pluripotent progenitor cells with the ability to generate cartilage, bone, muscle, tendon, ligament, and fat. However, recent evidence indicates that a major drawback of current cartilage- and intervertebral disc-tissue engineering is that human MSCs isolated from some arthritic patients (a clinically relevant source of stem cells) express type X collagen (a marker of chondrocyte hypertrophy associated with endochondral ossification) and osteogenic markers. Some studies have attempted to use growth factors to inhibit type X collagen expression, but none has addressed the possible effect of the chemical composition of the substratum on chondrocyte hypertrophy and osteogenesis. Here, we examine the growth and differentiation potential of human MSCs cultured on nitrogen (N)-rich plasma polymer layers (N-doped plasma-polymerized ethylene, containing up to 36% nitrogen; PPE:N). We show that PPE:N almost completely suppresses the expression not only of type X collagen, but also of osteogenic marker genes such as alkaline phosphatase, bone sialoprotein, and osteocalcin. In contrast, neither aggrecan nor type I collagen expression were significantly affected. These results indicate that PPE:N coatings may be suitable surfaces for inducing MSCs to a chondrocyte or disc-like phenotype for tissue engineering of cartilage or intervertebral discs, in which hypertrophy and osteogenesis are suppressed.
间充质干细胞(MSCs)是多能祖细胞,具有生成软骨、骨、肌肉、肌腱、韧带和脂肪的能力。然而,最近的证据表明,当前软骨和椎间盘组织工程的一个主要缺点是,从一些关节炎患者(临床上相关的干细胞来源)分离出的人类间充质干细胞表达X型胶原蛋白(一种与软骨内骨化相关的软骨细胞肥大标志物)和成骨标志物。一些研究试图使用生长因子来抑制X型胶原蛋白的表达,但没有一项研究探讨过基质化学成分对软骨细胞肥大和成骨的可能影响。在此,我们研究了在富含氮(N)的等离子体聚合物层(N掺杂的等离子体聚合乙烯,含氮量高达36%;PPE:N)上培养的人类间充质干细胞的生长和分化潜能。我们发现,PPE:N不仅几乎完全抑制了X型胶原蛋白的表达,还抑制了碱性磷酸酶、骨唾液蛋白和骨钙素等成骨标志物基因的表达。相比之下,聚集蛋白聚糖和I型胶原蛋白的表达均未受到显著影响。这些结果表明,PPE:N涂层可能是诱导间充质干细胞向软骨细胞或盘状表型分化的合适表面,用于软骨或椎间盘的组织工程,其中肥大和成骨受到抑制。