Cartilage Restoration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Tissue Eng Part B Rev. 2010 Feb;16(1):105-15. doi: 10.1089/ten.TEB.2009.0452.
Articular cartilage injury and degeneration are leading causes of disability. Animal studies are critically important to developing effective treatments for cartilage injuries. This review focuses on the use of animal models for the study of the repair and regeneration of focal cartilage defects. Animals commonly used in cartilage repair studies include murine, lapine, canine, caprine, porcine, and equine models. There are advantages and disadvantages to each model. Small animal rodent and lapine models are cost effective, easy to house, and useful for pilot and proof-of-concept studies. The availability of transgenic and knockout mice provide opportunities for mechanistic in vivo study. Athymic mice and rats are additionally useful for evaluating the cartilage repair potential of human cells and tissues. Their small joint size, thin cartilage, and greater potential for intrinsic healing than humans, however, limit the translational value of small animal models. Large animal models with thicker articular cartilage permit study of both partial thickness and full thickness chondral repair, as well as osteochondral repair. Joint size and cartilage thickness for canine, caprine, and mini-pig models remain significantly smaller than that of humans. The repair and regeneration of chondral and osteochondral defects of size and volume comparable to that of clinically significant human lesions can be reliably studied primarily in equine models. While larger animals may more closely approximate the human clinical situation, they carry greater logistical, financial, and ethical considerations. A multifactorial analysis of each animal model should be carried out when planning in vivo studies. Ultimately, the scientific goals of the study will be critical in determining the appropriate animal model.
关节软骨损伤和退变是导致残疾的主要原因。动物研究对于开发有效的软骨损伤治疗方法至关重要。本综述重点介绍了用于研究焦点软骨缺损修复和再生的动物模型的使用。常用于软骨修复研究的动物包括鼠类、兔类、犬类、山羊类、猪类和马类模型。每种模型都有其优缺点。小型动物啮齿类和兔类模型具有成本效益高、易于饲养以及适用于初步研究和概念验证研究等优点。转基因和基因敲除小鼠的可用性为体内机制研究提供了机会。无胸腺小鼠和大鼠还可用于评估人细胞和组织的软骨修复潜力。然而,由于其关节较小、软骨较薄,以及内在愈合能力比人类更强,限制了小型动物模型的转化价值。具有较厚关节软骨的大动物模型可用于研究部分厚度和全厚度软骨修复以及骨软骨修复。犬类、山羊类和小型猪模型的关节大小和软骨厚度仍明显小于人类。可主要在马类模型中可靠地研究与临床上有意义的人类病变大小和体积相当的软骨和骨软骨缺损的修复和再生。虽然较大的动物可能更接近人类的临床情况,但它们需要更多的后勤、财务和伦理考虑。在进行体内研究计划时,应对每种动物模型进行多因素分析。最终,研究的科学目标对于确定合适的动物模型至关重要。