2015 ISAKOS Biennial Congress ePoster #307

The Horse as a Model Animal for Cell Therapy of Tendon Disease: Comparing the Properties of Human and Equine Progenitor Cells

Annette Ahrberg, MD, Leipzig GERMANY
Janina Burk, DVM, Leipzig GERMANY
Claudia Gittel, MD, Vet., Leipzig GERMANY
Sandra Heller, MSC, Leipzig GERMANY
Aline Hillmann, DVM, Leipzig GERMANY
Felicitas Päbst, DVM, Leipzig GERMANY
Christoph Josten, Professor, Leipzig, Saxonia GERMANY
Walter Brehm, Prof, DVM, Leipzig GERMANY
Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, GERMANY

FDA Status Not Applicable

Summary: This study reveals that although human and equine MSC generally display similar properties, there are also differences between the cells from the two species, which should be taken into consideration in futuer research.

Abstract:

Introduction

The treatment of tendinopathy is one of the biggest challenges in orthopedic surgery. The horse as the athlete among the animals suffers from degenerative tendinopathy and ruptures just like human athletes. Equine patients have been treated with regenerative cell therapies with promising success for more than ten years, with most experiences existing in multipotent mesenchymal stromal cell (MSC) therapy for tendon disease. While translation to human medicine appears favorable and the horse is generally considered a highly suitable model animal for orthopedic research, knowledge is very limited concerning the comparability of equine MSC and their putative human counterpart. Therefore, the aim of this study was to compare functional and phenotypic properties of human and equine MSC and thus to improve transferability of results gained in the equine model.

Methods

Samples of adipose and tendon tissue were recovered from equine and human donors. Cells were isolated by enzymatic tissue digestion and subjected to proliferation, migration and trilineage differentiation assays, immunophenotyping by flow cytometry and gene expression analysis of tendon markers by real-time RT-PCR. Mann-Whitney-U tests were performed to analyze differences between the sample groups.

Results

While equine and human MSC generally exhibited similar phenotypes and behaviour, quantification of results revealed some differences between MSC from the different tissues as well as from the different species.
Plastic-adherent cells with a fibroblast-like morphology could be isolated from all samples. Further, cells from all samples were capable of multilineage differentiation, although the osteogenic potential of human tendon derived cells was limited in 4/9 samples. Immunophenotyping revealed a similar surface marker expression profile of human and equine cells which were positive for CD29, CD44, CD105, and negative for the recommended exclusion markers. Differences between MSC from the two species were evident regarding the cell yields and proliferation characteristics. While the yield of mononuclear cells per gram of tissue after the isolation procedure was higher in equine tissues (p<0.01), the yield of actual MSC per seeded mononuclear cells and culture days after the first passaging was similar for both tissues and both species. During the following passages, equine MSC proliferated more rapidly than human MSC, which was significant for the adipose derived cells (p<0.05). Furthermore, differences were found between the expression of tendon markers in human and equine MSC: Decorin and tenascin-C expression were lower in equine than in human MSC, while scleraxis expression was higher (p<0.05).

Conclusion

This study reveals that although human and equine MSC generally display similar properties, there are also differences between the cells from the two species. These differences should be taken into consideration when interpreting the data obtained in the equine model animal. The results of this study are fundamental for the future treatment of human tendinopathy with cell therapy.