Repeated intra-articular administration of equine allogeneic peripheral blood-derived mesenchymal stem cells does not induce a cellular and humoral immune response in horses.
Abstract: The use of mesenchymal stem cells (MSCs) for the treatment of equine joint disease is widely investigated because of their regenerative and immunomodulatory potential. Allogeneic MSCs provide a promising alternative to autologous MSCs, since the former are immediately available and enable a thorough donor screening. However, questions have been raised concerning the immunogenic potential of allogeneic MSCs, especially after repeated administration. Methods: Current retrospective study assessed the cellular and humoral immunogenicity of ten jumping and dressage horses with naturally occurring degenerative joint disease which were treated 3 times intra-articularly with a 1 mL stem cell suspension containing 1.4-2.5 million chondrogenic induced equine allogeneic peripheral blood-derived MSCs (ciMSCs) combined with 1 mL equine allogeneic plasma. Stem cells from 2 donor horses were used. Horses were clinically evaluated for joint effusion, presence of pain to palpation and skin surface temperature at the local injection site, joint range of motion, occurrence of adverse events and the presence of ectopic tissue. The cellular immune response was analyzed using a modified mixed lymphocyte reaction and the humoral immune response was investigated using a flow cytometric crossmatch assay by which the presence of alloantibodies against the ciMSCs was evaluated. Presence of anti-bovine serum albumin antibodies was detected via ELISA. Results: Clinical evaluation of the horses revealed no serious adverse effects or suspected adverse drug reactions and no ectopic tissue formation at the local injection site or in other areas of the body. Generally, repeated administration led to a decrease of horses with joint effusion of the affected joint. Pain to palpation, skin surface temperature and joint range of motion did not increase or even decreased after treatment administration. Allogeneic ciMSCs did not induce a cellular immune response and no alloantibodies were detected in the recipients' serum, regardless the presence of BSA antibodies in 70 % of the horses. Conclusions: Repeated intra-articular injections with allogeneic equine ciMSCs did not elicit clinically relevant adverse events. Furthermore, current study indicates the absence of a cellular or a humoral immune response following repeated intra-articular injections.
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
Publication Date: 2021-08-02 PubMed ID: 34365135DOI: 10.1016/j.vetimm.2021.110306Google Scholar: Lookup
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- Journal Article
- Adverse Effects
- Clinical Examination
- Clinical Study
- Degenerative Joint Disease
- Dressage
- Equine Diseases
- Equine Health
- Flow Cytometry
- Horses
- Immune Response
- Immunoglobulin G
- Immunology
- Intra-Articular Injection
- Joint Health
- Mesenchymal Cells
- Regenerative Medicine
- Retrospective Study
- Stem Cells
- Veterinary Medicine
- Veterinary Research
Summary
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This research paper looked at whether the repeated use of allogeneic mesenchymal stem cells (MSCs) for the treatment of joint disease in horses provoked an immune response, and concluded that it did not.
Research Goals
- The goal of this research was to investigate whether allogeneic, or non-self, mesenchymal stem cells (MSCs) provoke an immune response in horses that receive repeated intra-articular injections of the cells.
Reasons for Study
- MSCs are potentially a very potent tool for treating joint disease in horses. However, questions have been raised concerning whether or not MSCs might provoke an immune response in horses, especially following repeated administrations into the joints.
Methods
- The researchers worked with ten horses who were experiencing degenerative joint disease. Each horse received three intra-articular injections of a stem cell suspension that was made up of chondrogenic induced equine allogeneic peripheral blood-derived MSCs (ciMSCs) combined with equine allogeneic plasma.
- The researchers then evaluated the horses for various clinical signs such as effusion in the joints, pain upon palpation, skin surface temperature at the injection site, joint range of motion, adverse events, and the presence of any ectopic tissue.
- The immune response was assessed by testing for the presence of alloantibodies against the ciMSCs in the recipient’s serum, and detecting anti-bovine serum albumin antibodies.
Results
- The results showed that the repeated administration of allogeneic ciMSCs did not induce a cellular immune response nor cause the formation of alloantibodies in the horses’ serum.
- Clinically, the horses did not experience adverse effects or suspected adverse drug reactions, and no ectopic tissue formation was observed.
- Generally, repeated administration improved the condition of the joints, pain and palpation.
Conclusions
- In conclusion, the study found that repeating intra-articular injections with allogeneic equine ciMSCs did not elicit adverse events or provoke a cellular or humoral immune response in horses.
Cite This Article
APA
Van Hecke L, Magri C, Duchateau L, Beerts C, Geburek F, Suls M, Da Dalt L, Patruno M, Saunders J, Broeckx SY, Depuydt E, Spaas JH.
(2021).
Repeated intra-articular administration of equine allogeneic peripheral blood-derived mesenchymal stem cells does not induce a cellular and humoral immune response in horses.
Vet Immunol Immunopathol, 239, 110306.
https://doi.org/10.1016/j.vetimm.2021.110306 Publication
Researcher Affiliations
- Global Stem Cell Technology NV, Part of Boehringer Ingelheim, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: lore.van_hecke@boehringer-ingelheim.com.
- Veterinary Innovation Alliance CV, Berkenbroekstraat 1, 3960, Bree, Belgium. Electronic address: carmelo@vianovaequine.com.
- Biometrics Research Group, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Electronic address: luc.duchateau@UGent.be.
- Global Stem Cell Technology NV, Part of Boehringer Ingelheim, Noorwegenstraat 4, 9940, Evergem, Belgium; Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: charlotte.beerts.ext@boehringer-ingelheim.com.
- Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany. Electronic address: florian.geburek@tiho-hannover.de.
- Veterinary Innovation Alliance CV, Berkenbroekstraat 1, 3960, Bree, Belgium; Suls Equine Veterinary Services BV, Kazernelaan 144, 6006 SP, Weert, the Netherlands. Electronic address: marc@drsuls.com.
- Department of Comparative Biomedicine and Food Science BCA, University of Padova, Viale dell'Università, 16, 35020, Agripolis-Legnaro, Padova, Italy. Electronic address: laura.dadalt@unipd.it.
- Department of Comparative Biomedicine and Food Science BCA, University of Padova, Viale dell'Università, 16, 35020, Agripolis-Legnaro, Padova, Italy. Electronic address: marco.pat@unipd.it.
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: Jimmy.Saunders@UGent.be.
- Global Stem Cell Technology NV, Part of Boehringer Ingelheim, Noorwegenstraat 4, 9940, Evergem, Belgium. Electronic address: sarah.broeckx@boehringer-ingelheim.com.
- Global Stem Cell Technology NV, Part of Boehringer Ingelheim, Noorwegenstraat 4, 9940, Evergem, Belgium; Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. Electronic address: eva.depuydt@boehringer-ingelheim.com.
- Global Stem Cell Technology NV, Part of Boehringer Ingelheim, Noorwegenstraat 4, 9940, Evergem, Belgium; Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Electronic address: jan.spaas@boehringer-ingelheim.com.
MeSH Terms
- Animals
- Hematopoietic Stem Cell Transplantation / veterinary
- Horses
- Immunity, Cellular
- Immunity, Humoral
- Injections, Intra-Articular
- Mesenchymal Stem Cells
- Retrospective Studies
Citations
This article has been cited 9 times.- Cequier A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Serrano MB, Zaragoza MP, Romero A, Rodellar C, Barrachina L. The systemic cellular immune response against allogeneic mesenchymal stem cells is influenced by inflammation, differentiation and MHC compatibility: in vivo study in the horse. Front Vet Sci 2024;11:1391872.
- Reis IL, Lopes B, Sousa P, Sousa AC, Rêma A, Caseiro AR, Briote I, Rocha AM, Pereira JP, Mendonça CM, Santos JM, Lamas L, Atayde LM, Alvites RD, Maurício AC. Case report: Equine metacarpophalangeal joint partial and full thickness defects treated with allogenic equine synovial membrane mesenchymal stem/stromal cell combined with umbilical cord mesenchymal stem/stromal cell conditioned medium. Front Vet Sci 2024;11:1403174.
- Jakobsen KK, Lynggaard CD, Paaske N, Carlander AF, Kastrup J, Hauge AW, Christensen R, Grønhøj C, Buchwald CV. Long-Term Outcome Following Treatment With Allogeneic Mesenchymal Stem/Stromal Cells for Radiation-Induced Hyposalivation and Xerostomia. Stem Cells Transl Med 2024 Jun 14;13(6):515-521.
- Canonici F, Cocumelli C, Cersini A, Marcoccia D, Zepparoni A, Altigeri A, Caciolo D, Roncoroni C, Monteleone V, Innocenzi E, Alimonti C, Ghisellini P, Rando C, Pechkova E, Eggenhöffner R, Scicluna MT, Barbaro K. Articular Cartilage Regeneration by Hyaline Chondrocytes: A Case Study in Equine Model and Outcomes. Biomedicines 2023 May 31;11(6).
- Punzón E, García-Castillo M, Rico MA, Padilla L, Pradera A. Local, systemic and immunologic safety comparison between xenogeneic equine umbilical cord mesenchymal stem cells, allogeneic canine adipose mesenchymal stem cells and placebo: a randomized controlled trial. Front Vet Sci 2023;10:1098029.
- Lei L, Meng L, Changqing X, Chen Z, Gang Y, Shiyuan F. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights. Open Life Sci 2022;17(1):695-709.
- Cequier A, Romero A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Zaragoza P, Rodellar C, Barrachina L. Equine Mesenchymal Stem Cells Influence the Proliferative Response of Lymphocytes: Effect of Inflammation, Differentiation and MHC-Compatibility. Animals (Basel) 2022 Apr 11;12(8).
- Depuydt E, Broeckx SY, Chiers K, Patruno M, Da Dalt L, Duchateau L, Saunders J, Pille F, Martens A, Van Hecke L, Spaas JH. Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries. Front Vet Sci 2021;8:789293.
- Melotti L, Carolo A, Elshazly N, Boesso F, Da Dalt L, Gabai G, Perazzi A, Iacopetti I, Patruno M. Case Report: Repeated Intralesional Injections of Autologous Mesenchymal Stem Cells Combined With Platelet-Rich Plasma for Superficial Digital Flexor Tendon Healing in a Show Jumping Horse. Front Vet Sci 2022;9:843131.
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