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接受自体软骨细胞移植患者的软骨细胞与骨关节炎患者软骨细胞中标记基因表达的比较。

Comparison of marker gene expression in chondrocytes from patients receiving autologous chondrocyte transplantation versus osteoarthritis patients.

作者信息

Stoop Reinout, Albrecht Dirk, Gaissmaier Christoph, Fritz Jürgen, Felka Tino, Rudert Maximilian, Aicher Wilhelm K

机构信息

NMI Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstrasse, 72770 Reutlingen, Germany.

出版信息

Arthritis Res Ther. 2007;9(3):R60. doi: 10.1186/ar2218.

Abstract

Currently, autologous chondrocyte transplantation (ACT) is used to treat traumatic cartilage damage or osteochondrosis dissecans, but not degenerative arthritis. Since substantial refinements in the isolation, expansion and transplantation of chondrocytes have been made in recent years, the treatment of early stage osteoarthritic lesions using ACT might now be feasible. In this study, we determined the gene expression patterns of osteoarthritic (OA) chondrocytes ex vivo after primary culture and subculture and compared these with healthy chondrocytes ex vivo and with articular chondrocytes expanded for treatment of patients by ACT. Gene expression profiles were determined using quantitative RT-PCR for type I, II and X collagen, aggrecan, IL-1beta and activin-like kinase-1. Furthermore, we tested the capability of osteoarthritic chondrocytes to generate hyaline-like cartilage by implanting chondrocyte-seeded collagen scaffolds into immunodeficient (SCID) mice. OA chondrocytes ex vivo showed highly elevated levels of IL-1beta mRNA, but type I and II collagen levels were comparable to those of healthy chondrocytes. After primary culture, IL-1beta levels decreased to baseline levels, while the type II and type I collagen mRNA levels matched those found in chondrocytes used for ACT. OA chondrocytes generated type II collagen and proteoglycan-rich cartilage transplants in SCID mice. We conclude that after expansion under suitable conditions, the cartilage of OA patients contains cells that are not significantly different from those from healthy donors prepared for ACT. OA chondrocytes are also capable of producing a cartilage-like tissue in the in vivo SCID mouse model. Thus, such chondrocytes seem to fulfil the prerequisites for use in ACT treatment.

摘要

目前,自体软骨细胞移植(ACT)用于治疗创伤性软骨损伤或剥脱性骨软骨炎,但不用于治疗退行性关节炎。鉴于近年来在软骨细胞的分离、扩增和移植方面取得了重大进展,现在使用ACT治疗早期骨关节炎病变可能是可行的。在本研究中,我们测定了原代培养和传代培养后体外培养的骨关节炎(OA)软骨细胞的基因表达模式,并将其与体外健康软骨细胞以及用于ACT治疗患者而扩增的关节软骨细胞进行比较。使用定量RT-PCR测定I型、II型和X型胶原蛋白、聚集蛋白聚糖、IL-1β和激活素样激酶-1的基因表达谱。此外,我们通过将接种软骨细胞的胶原支架植入免疫缺陷(SCID)小鼠体内,测试了骨关节炎软骨细胞生成透明样软骨的能力。体外培养的OA软骨细胞显示IL-1β mRNA水平高度升高,但I型和II型胶原蛋白水平与健康软骨细胞相当。原代培养后,IL-1β水平降至基线水平,而II型和I型胶原蛋白mRNA水平与ACT所用软骨细胞中的水平相当。OA软骨细胞在SCID小鼠体内生成了富含II型胶原蛋白和蛋白聚糖的软骨移植体。我们得出结论,在合适条件下扩增后,OA患者的软骨所含细胞与为ACT准备的健康供体的细胞没有显著差异。OA软骨细胞在体内SCID小鼠模型中也能够产生类似软骨的组织。因此,这类软骨细胞似乎满足ACT治疗的先决条件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/145e/2206334/7ff1545bbb0e/ar2218-1.jpg

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