Yves Debosschere1, Eva Depuydt2, Glenn Pauwelyn3, Charlotte Beerts4, Lore Van Hecke5, Leen Verhaert6, Luc Duchateau7, Jimmy Saunders8, Liesa Tack9, Jan H Spaas10. 1. Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Electronic address: yves@vetdent.be. 2. Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: eva.depuydt@anacura.com. 3. Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: glenn.pauwelyn@anacura.com. 4. Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: charlotte.beerts@anacura.com. 5. Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: lore.vanhecke@anacura.com. 6. Department of Small Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Electronic address: verhaert.leen@skynet.be. 7. Biometrics Research Center, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Electronic address: luc.duchateau@ugent.be. 8. Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Electronic address: jimmy.saunders@ugent.be. 9. Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: liesa.tack@anacura.com. 10. Department of Medical Imaging and Orthopedics of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium; Global Stem Cell Technology NV, Anacura Group, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: jan.spaas@anacura.com.
Abstract
OBJECTIVE: Due to the immunomodulatory properties of mesenchymal stem cells (MSCs) through stimulation of endogenous immune cells by paracrine signals and cell contact, they have been proposed as alternative treatment option for many inflammatory and immune-mediated diseases in veterinary medicine. However, the long-term cultivation possibilities of feline MSCs are currently compromised due to a restricted proliferation capacity. Therefore, the xenogeneic use of equine peripheral blood-derived MSCs (ePB-MSCs) would present an interesting alternative thanks to their superior cultivation properties. To the authors' knowledge, there are currently no safety reports concerning the xenogeneic use of ePB-MSCs in cats. Therefore, the overall goal of this preliminary study was to investigate if ePB-MSCs can safely be administered in healthy cats and by extension evaluating their immunogenic and immunomodulatory properties. METHODS: Ten healthy cats were intravenously (i.v.) injected with 3 × 105 ePB-MSCs at three time points (T0, T1, T2). All cats were daily inspected by the caretaker and underwent a physical examination with hematological and biochemical analysis at day 0 (T0), week 2 (T1), week 4 (T2) and week 6 (T3) by a veterinarian. Furthermore, a modified mixed lymphocyte reaction (MLR) was performed at T0 and T3 for each cat in order to evaluate immunogenic and immunomodulatory properties of the ePB-MSCs RESULTS: No adverse clinical effects could be detected following repeated i.v. administration of ePB-MSCs in all cats. Significant lower protein (T1: P-value = 0.002; T2: P-value > 0.001; T3: P-value = 0.004) and albumin levels (T1: P-value = 0.003; T2: P-value = 0.001) were seen after repeated administration of ePB-MSCs, compared to T0. However, all biochemical and hematological parameters stayed within clinical acceptance level. In addition, the repeated injections did not induce a cellular immune response before and after repeated ePB-MSCs administration. Furthermore, convincing immunomodulatory properties of ePB-MSCs on feline peripheral blood mononuclear cells were confirmed in the MLR-assay CONCLUSION: This preliminary study demonstrates that ePB-MSCs can safely be administered in healthy cats and provide a promising alternative for the treatment of various inflammatory diseases in cats.
OBJECTIVE: Due to the immunomodulatory properties of mesenchymal stem cells (MSCs) through stimulation of endogenous immune cells by paracrine signals and cell contact, they have been proposed as alternative treatment option for many inflammatory and immune-mediated diseases in veterinary medicine. However, the long-term cultivation possibilities of feline MSCs are currently compromised due to a restricted proliferation capacity. Therefore, the xenogeneic use of equine peripheral blood-derived MSCs (ePB-MSCs) would present an interesting alternative thanks to their superior cultivation properties. To the authors' knowledge, there are currently no safety reports concerning the xenogeneic use of ePB-MSCs in cats. Therefore, the overall goal of this preliminary study was to investigate if ePB-MSCs can safely be administered in healthy cats and by extension evaluating their immunogenic and immunomodulatory properties. METHODS: Ten healthy cats were intravenously (i.v.) injected with 3 × 105 ePB-MSCs at three time points (T0, T1, T2). All cats were daily inspected by the caretaker and underwent a physical examination with hematological and biochemical analysis at day 0 (T0), week 2 (T1), week 4 (T2) and week 6 (T3) by a veterinarian. Furthermore, a modified mixed lymphocyte reaction (MLR) was performed at T0 and T3 for each cat in order to evaluate immunogenic and immunomodulatory properties of the ePB-MSCs RESULTS: No adverse clinical effects could be detected following repeated i.v. administration of ePB-MSCs in all cats. Significant lower protein (T1: P-value = 0.002; T2: P-value > 0.001; T3: P-value = 0.004) and albumin levels (T1: P-value = 0.003; T2: P-value = 0.001) were seen after repeated administration of ePB-MSCs, compared to T0. However, all biochemical and hematological parameters stayed within clinical acceptance level. In addition, the repeated injections did not induce a cellular immune response before and after repeated ePB-MSCs administration. Furthermore, convincing immunomodulatory properties of ePB-MSCs on feline peripheral blood mononuclear cells were confirmed in the MLR-assay CONCLUSION: This preliminary study demonstrates that ePB-MSCs can safely be administered in healthy cats and provide a promising alternative for the treatment of various inflammatory diseases in cats.
Authors: Eva Depuydt; Sarah Y Broeckx; Koen Chiers; Marco Patruno; Laura Da Dalt; Luc Duchateau; Jimmy Saunders; Frederik Pille; Ann Martens; Lore Van Hecke; Jan H Spaas Journal: Front Vet Sci Date: 2022-02-24