Division of Trauma and Orthopaedic Surgery, Cambridge University, Cambridge, UK.
Animal Health Trust, Newmarket, UK.
Cell Biol Toxicol. 2020 Apr;36(2):103-114. doi: 10.1007/s10565-020-09521-9. Epub 2020 Mar 23.
Large animal models have been widely used to facilitate the translation of mesenchymal stem cells (MSC) from the laboratory to patient. MSC, with their multi-potent capacity, have been proposed to have therapeutic benefits in a number of pathological conditions. Laboratory studies allow the investigation of cellular and molecular interactions, while small animal models allow initial 'proof of concept' experiments. Large animals (dogs, pigs, sheep, goats and horses) are more similar physiologically and structurally to man. These models have allowed clinically relevant assessments of safety, efficacy and dosing of different MSC sources prior to clinical trials. In this review, we recapitulate the use of large animal models to facilitate the use of MSC to treat myocardial infarction-an example of one large animal model being considered the 'gold standard' for research and osteoarthritis-an example of the complexities of using different large animal models in a multifactorial disease. These examples show how large animals can provide a research platform that can be used to evaluate the value of cell-based therapies and facilitate the process of 'bench to bedside'.
大型动物模型已被广泛用于促进间充质干细胞(MSC)从实验室向患者的转化。MSC 具有多能性,被认为在多种病理情况下具有治疗益处。实验室研究允许研究细胞和分子相互作用,而小动物模型允许进行初步的“概念验证”实验。大型动物(狗、猪、羊、山羊和马)在生理和结构上与人类更为相似。这些模型允许在临床试验前对不同 MSC 来源的安全性、疗效和剂量进行临床相关评估。在这篇综述中,我们总结了使用大型动物模型来促进 MSC 治疗心肌梗死的应用——其中一个大型动物模型被认为是研究的“金标准”,以及治疗骨关节炎——使用不同的大型动物模型在多因素疾病中的复杂性的例子。这些例子表明,大型动物可以提供一个研究平台,用于评估基于细胞的治疗方法的价值,并促进“从实验室到病床”的转化过程。