Safety assessment of equine allogeneic tenogenic primed mesenchymal stem cells in horses with naturally occurring tendon and ligament injuries

Stephanie Carlier; Eva Depuydt; Lore Van Hecke; Ann Martens; Jimmy Saunders; Jan H Spaas

doi:10.3389/fvets.2024.1282697

Safety assessment of equine allogeneic tenogenic primed mesenchymal stem cells in horses with naturally occurring tendon and ligament injuries

Front Vet Sci. 2024 Feb 26:11:1282697. doi: 10.3389/fvets.2024.1282697. eCollection 2024.

Authors

Stephanie Carlier^{1

2

3}, Eva Depuydt⁴, Lore Van Hecke⁴, Ann Martens², Jimmy Saunders³, Jan H Spaas^{3

5}

Affiliations

¹ Stephanie Carlier, Kortrijk, Belgium.
² Department of Large Animal Surgery, Anaesthesia and Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
³ Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁴ Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
⁵ Boehringer Ingelheim Animal Health USA, Athens, GA, United States.

Abstract

Background: Mesenchymal stem cells provide a valuable treatment option in orthopedic injuries in horses.

Objectives: The aim of this study was to evaluate the hematological, biochemical, immunological and immunomodulatory parameters following intralesional treatment with tenogenic primed equine allogeneic peripheral blood-derived mesenchymal stem cells (tpMSCs) in client-owned horses with naturally occurring superficial digital flexor tendon (SDFT) and suspensory ligament (SL) injuries.

Methods: The immunogenicity and immunomodulatory capacities of tpMSCs were assessed in a modified mixed lymphocyte reaction, including peripheral blood mononuclear cells (PBMCs) of 14 horses with SDFT and SL injuries after treatment with tpMSCs. In a second study, 18 horses with SDFT and SL injuries received either an intralesional injection with tpMSCs (n = 9) or no treatment (n = 9).

Results: The tpMSCs did not provoke a cellular immune response (p < 0.001) and were able to immunomodulate stimulated T lymphocytes (p < 0.001) in vitro. Therapeutic use of tpMSCs did not result in relevant hematologic or biochemical abnormalities.

Main limitations: Both studies had a small sample size. No statistical analyses were performed in the second study. Fibrinogen was only analyzed in a single horse prior to treatment.

Conclusion: Co-incubation of tpMSCs and PBMCs of horses that have been previously exposed to tpMSCs did not elicit a cellular immune response and tpMSCs were able to immunomodulate stimulated T lymphocytes. Intralesional treatment with tpMSCs did not provoke abnormal changes in hematological and biochemical parameters.

Keywords: desmitis; equine; mesenchymal stem cell; primed MSCs; tendonitis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Boehringer-Ingelheim and supported by a grant from the Flanders Innovation & Entrepreneurship (Vlaio project number HBC.2020.2227).