Li Wan-Ju, Chiang Hongsen, Kuo Tzong-Fu, Lee Hsuan-Shu, Jiang Ching-Chuan, Tuan Rocky S
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-8022, USA.
J Tissue Eng Regen Med. 2009 Jan;3(1):1-10. doi: 10.1002/term.127.
The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(epsilon-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair.
本研究的目的是评估一种接种细胞的纳米纤维支架在体内修复软骨的效果。我们使用了可生物降解的聚己内酯(PCL)纳米纤维支架,接种同种异体软骨细胞或异种人骨髓间充质干细胞(MSC),或无细胞的PCL支架,以未植入任何材料作为对照,来修复猪模型中7毫米全层医源性软骨缺损。植入6个月后,与其他组相比,接种MSC的构建体在缺损处显示出最完全的修复。宏观上,接种MSC的构建体再生出透明软骨样组织并恢复了光滑的软骨表面,而接种软骨细胞的构建体大多产生纤维软骨样组织,表面软骨轮廓不连续。在无细胞构建体和未植入对照组中发现含有纤维软骨或纤维组织的不完全修复。定量组织学评估显示,接种软骨细胞和MSC的构建体的总体评分高于无细胞构建体和未植入组。力学测试表明,接种MSC的构建体产生的再生软骨的平衡压缩应力最高,为1.5MPa,而接种软骨细胞的构建体为1.2MPa,无细胞构建体为1.0MPa,未植入组为0.2MPa。未观察到对同种异体和异种来源的再生软骨有免疫反应的证据,这可能与MSC的免疫抑制活性有关,表明MSC同种异体或异种移植用于基于细胞的治疗是可行的。综上所述,我们的结果表明,接种MSC的可生物降解纳米纤维支架能有效地在体内修复软骨缺损,并且目前的方法在软骨修复方面很有前景。