Abstract

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’.

Highlights

  • Animals are used in research where there is a need to study the effect of a treatment on a whole tissue or living organism (Barré-Sinoussi and Montagutelli 2015)

  • Large animal models have been widely used to facilitate the translation of mesenchymal stem cells (MSC) from the laboratory to patient

  • The aim of this review is to illustrate how MSC have been translated to man through large animal models

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Summary

Introduction

Animals are used in research where there is a need to study the effect of a treatment on a whole tissue or living organism (Barré-Sinoussi and Montagutelli 2015). Xiang et al (2009) showed that the application of MSC conditioned media to neonatal rat cardiomyocytes and reduced cardiomyocyte apoptosis via effects on the mitochondrial pathway (Xiang et al 2009) Following these encouraging in vitro results, subsequent small animal studies showed that MSC had therapeutic efficacy in a MI model. Whilst small animal studies have been useful to show proof of concept for the use of MSC to treat MI, it has been necessary to use large animal models, the porcine ischaemic MI model, to confirm the suitability of this cell therapy in man. Whilst MSC have been used in small animal OA models as described above, large animals offer significant We show the type of heart disease treated, the source of the MSC, the cell number and the study outcomes. This data is useful in considering the clinical translation of MSC as there is ongoing discussion as to the need for MSC priming/conditioning prior to use (Succar et al 2016; Barrachina et al 2018)

Method of OA induction
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