Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration.
Abstract: Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs' treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.
Publication Date: 2018-06-06 PubMed ID: 29977305PubMed Central: PMC6011062DOI: 10.1155/2018/1073705Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article investigates the potential of using mesenchymal stem cells (MSCs) drawn from horse synovial fluid (SFMSCs) to regenerate articular cartilage, as compared to those taken from bone marrow (BMMSCs). The study utilises a preclinical animal model to test the concept, demonstrating positive results in healing of articular cartilage, particularly when SFMSCs are used.
Research Methodology
- The scientists started by using horses as their source of MSCs, which were collected from both bone marrow and synovial fluid from the same donor.
- The cells underwent an analysis in the laboratory to confirm an increased expression of COMP in SFMSCs at day 14. COMP or Cartilage Oligomeric Matrix Protein is a biomarker indicating healthy joint cartilage.
- An experiment was then carried out where these cells were encapsulated into a neutral agarose scaffold construct – a device that can support the growth of new cells – before being implanted into a cartilage defect in a rat’s femur.
- They checked one week after this implantation to confirm the MSCs were present at the injury site. They undertook a further evaluation 12 weeks post-implantation to assess the macroscopic and histologic state of the affected area.
Key Findings
- The MSCs-treated knees showed superior healing to the untreated control knees
- Of particular note, the SFMSC-treated knees demonstrated a significantly higher expression of collagen type II, or Col II. This is a protein abundant in healthy cartilage, leads researchers to conclude that hyaline, or healthy, cartilage was present in the healed area.
- The research suggests that SFMSCs could be a feasible treatment for osteochondral defects. However, the properties of these cells would need to be tested prior to clinical application.
Implication and Future Directions
- This study provides promising evidence that equine SFMSCs have potential to treat joint defects and contribute to articular cartilage regeneration.
- This opens a path for further investigations into practical clinical applications of SFMSCs, and could contribute to more effective therapies for joint diseases and injuries in humans.
- Yet, more comprehensive studies are required to understand the full healing potential and safety of these cells in treating osteochondral defects. The potential variability of stem cell properties from donor to donor should also be taken into account in future studies.
Cite This Article
APA
Zayed M, Newby S, Misk N, Donnell R, Dhar M.
(2018).
Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration.
Stem Cells Int, 2018, 1073705.
https://doi.org/10.1155/2018/1073705 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
- Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
- Department of Surgery, College of Veterinary Medicine, Assuit University, Asyut 71526, Egypt.
- Biomedical and Diagnostic Services, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
- Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
References
This article includes 45 references
- Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation.. Instr Course Lect 1998;47:487-504.
- Gobbi A, Nunag P, Malinowski K. Treatment of full thickness chondral lesions of the knee with microfracture in a group of athletes.. Knee Surg Sports Traumatol Arthrosc 2005 Apr;13(3):213-21.
- Johnson LL. Arthroscopic abrasion arthroplasty historical and pathologic perspective: present status.. Arthroscopy 1986;2(1):54-69.
- Falah M, Nierenberg G, Soudry M, Hayden M, Volpin G. Treatment of articular cartilage lesions of the knee.. Int Orthop 2010 Jun;34(5):621-30.
- Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.. Osteoarthritis Cartilage 2002 Jun;10(6):432-63.
- Cohen NP, Foster RJ, Mow VC. Composition and dynamics of articular cartilage: structure, function, and maintaining healthy state.. J Orthop Sports Phys Ther 1998 Oct;28(4):203-15.
- Matricali GA, Dereymaeker GP, Luyten FP. Donor site morbidity after articular cartilage repair procedures: a review.. Acta Orthop Belg 2010 Oct;76(5):669-74.
- Lee WY, Wang B. Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives.. J Orthop Translat 2017 Apr;9:76-88.
- Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source.. Arthritis Rheum 2005 Aug;52(8):2521-9.
- Mohan N, Nair PD, Tabata Y. Growth factor-mediated effects on chondrogenic differentiation of mesenchymal stem cells in 3D semi-IPN poly(vinyl alcohol)-poly(caprolactone) scaffolds.. J Biomed Mater Res A 2010 Jul;94(1):146-59.
- Tuli R, Tuli S, Nandi S, Huang X, Manner PA, Hozack WJ, Danielson KG, Hall DJ, Tuan RS. Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk.. J Biol Chem 2003 Oct 17;278(42):41227-36.
- Barry F, Boynton RE, Liu B, Murphy JM. Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components.. Exp Cell Res 2001 Aug 15;268(2):189-200.
- Solchaga LA, Penick KJ, Welter JF. Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks.. Methods Mol Biol 2011;698:253-78.
- Orth P, Rey-Rico A, Venkatesan JK, Madry H, Cucchiarini M. Current perspectives in stem cell research for knee cartilage repair.. Stem Cells Cloning 2014;7:1-17.
- Jones BA, Pei M. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.. Tissue Eng Part B Rev 2012 Aug;18(4):301-11.
- Zayed M, Caniglia C, Misk N, Dhar MS. Donor-Matched Comparison of Chondrogenic Potential of Equine Bone Marrow- and Synovial Fluid-Derived Mesenchymal Stem Cells: Implications for Cartilage Tissue Regeneration.. Front Vet Sci 2016;3:121.
- Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair.. Tissue Eng Part B Rev 2010 Feb;16(1):105-15.
- Cook JL, Hung CT, Kuroki K, Stoker AM, Cook CR, Pfeiffer FM, Sherman SL, Stannard JP. Animal models of cartilage repair.. Bone Joint Res 2014;3(4):89-94.
- McIlwraith CW, Fortier LA, Frisbie DD, Nixon AJ. Equine Models of Articular Cartilage Repair.. Cartilage 2011 Oct;2(4):317-26.
- Zayed MN, Schumacher J, Misk N, Dhar MS. Effects of pro-inflammatory cytokines on chondrogenesis of equine mesenchymal stromal cells derived from bone marrow or synovial fluid.. Vet J 2016 Nov;217:26-32.
- Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow.. Stem Cells 2007 Jun;25(6):1384-92.
- Elkhenany H, Bourdo S, Hecht S, Donnell R, Gerard D, Abdelwahed R, Lafont A, Alghazali K, Watanabe F, Biris AS, Anderson D, Dhar M. Graphene nanoparticles as osteoinductive and osteoconductive platform for stem cell and bone regeneration.. Nanomedicine 2017 Oct;13(7):2117-2126.
- Pineda S, Pollack A, Stevenson S, Goldberg V, Caplan A. A semiquantitative scale for histologic grading of articular cartilage repair.. Acta Anat (Basel) 1992;143(4):335-40.
- Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J. A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee.. J Bone Joint Surg Br 2003 Mar;85(2):223-30.
- Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grøntvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial.. J Bone Joint Surg Am 2004 Mar;86(3):455-64.
- Roberts S, McCall IW, Darby AJ, Menage J, Evans H, Harrison PE, Richardson JB. Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology.. Arthritis Res Ther 2003;5(1):R60-73.
- Wood JJ, Malek MA, Frassica FJ, Polder JA, Mohan AK, Bloom ET, Braun MM, Coté TR. Autologous cultured chondrocytes: adverse events reported to the United States Food and Drug Administration.. J Bone Joint Surg Am 2006 Mar;88(3):503-7.
- Im GI, Kim DY, Shin JH, Hyun CW, Cho WH. Repair of cartilage defect in the rabbit with cultured mesenchymal stem cells from bone marrow.. J Bone Joint Surg Br 2001 Mar;83(2):289-94.
- Jung M, Kaszap B, Redöhl A, Steck E, Breusch S, Richter W, Gotterbarm T. Enhanced early tissue regeneration after matrix-assisted autologous mesenchymal stem cell transplantation in full thickness chondral defects in a minipig model.. Cell Transplant 2009;18(8):923-32.
- de Sousa EB, Casado PL, Moura Neto V, Duarte ME, Aguiar DP. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives.. Stem Cell Res Ther 2014 Oct 3;5(5):112.
- Mak J, Jablonski CL, Leonard CA, Dunn JF, Raharjo E, Matyas JR, Biernaskie J, Krawetz RJ. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model.. Sci Rep 2016 Mar 17;6:23076.
- Sekiya I, Ojima M, Suzuki S, Yamaga M, Horie M, Koga H, Tsuji K, Miyaguchi K, Ogishima S, Tanaka H, Muneta T. Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis.. J Orthop Res 2012 Jun;30(6):943-9.
- Isobe Y, Koyama N, Nakao K, Osawa K, Ikeno M, Yamanaka S, Okubo Y, Fujimura K, Bessho K. Comparison of human mesenchymal stem cells derived from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous tooth pulp.. Int J Oral Maxillofac Surg 2016 Jan;45(1):124-31.
- Haleem-Smith H, Calderon R, Song Y, Tuan RS, Chen FH. Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells.. J Cell Biochem 2012 Apr;113(4):1245-52.
- Christensen LH. Host tissue interaction, fate, and risks of degradable and nondegradable gel fillers.. Dermatol Surg 2009 Oct;35 Suppl 2:1612-9.
- Huang CY, Reuben PM, D'Ippolito G, Schiller PC, Cheung HS. Chondrogenesis of human bone marrow-derived mesenchymal stem cells in agarose culture.. Anat Rec A Discov Mol Cell Evol Biol 2004 May;278(1):428-36.
- Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects.. Tissue Eng Part A 2012 Jul;18(13-14):1479-89.
- Suzawa Y, Kubo N, Iwai S, Yura Y, Ohgushi H, Akashi M. Biomineral/Agarose Composite Gels Enhance Proliferation of Mesenchymal Stem Cells with Osteogenic Capability.. Int J Mol Sci 2015 Jun 23;16(6):14245-58.
- Varoni E, Tschon M, Palazzo B, Nitti P, Martini L, Rimondini L. Agarose gel as biomaterial or scaffold for implantation surgery: characterization, histological and histomorphometric study on soft tissue response.. Connect Tissue Res 2012;53(6):548-54.
- Chung JY, Song M, Ha CW, Kim JA, Lee CH, Park YB. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model.. Stem Cell Res Ther 2014 Mar 19;5(2):39.
- Guan M, Yao W, Liu R, Lam KS, Nolta J, Jia J, Panganiban B, Meng L, Zhou P, Shahnazari M, Ritchie RO, Lane NE. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass.. Nat Med 2012 Feb 5;18(3):456-62.
- Niemeyer P, Schönberger TS, Hahn J, Kasten P, Fellenberg J, Suedkamp N, Mehlhorn AT, Milz S, Pearce S. Xenogenic transplantation of human mesenchymal stem cells in a critical size defect of the sheep tibia for bone regeneration.. Tissue Eng Part A 2010 Jan;16(1):33-43.
- Paul A, Srivastava S, Chen G, Shum-Tim D, Prakash S. Functional assessment of adipose stem cells for xenotransplantation using myocardial infarction immunocompetent models: comparison with bone marrow stem cells.. Cell Biochem Biophys 2013 Nov;67(2):263-73.
- Sekiya I, Muneta T, Horie M, Koga H. Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.. Clin Orthop Relat Res 2015 Jul;473(7):2316-26.
- Koga H, Shimaya M, Muneta T, Nimura A, Morito T, Hayashi M, Suzuki S, Ju YJ, Mochizuki T, Sekiya I. Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect.. Arthritis Res Ther 2008;10(4):R84.
Citations
This article has been cited 14 times.- Leal Reis I, Lopes B, Sousa P, Sousa AC, Branquinho M, Caseiro AR, Pedrosa SS, Rêma A, Oliveira C, Porto B, Atayde L, Amorim I, Alvites R, Santos JM, Maurício AC. Allogenic Synovia-Derived Mesenchymal Stem Cells for Treatment of Equine Tendinopathies and Desmopathies-Proof of Concept. Animals (Basel) 2023 Apr 11;13(8).
- Lesage C, Lafont M, Guihard P, Weiss P, Guicheux J, Delplace V. Material-Assisted Strategies for Osteochondral Defect Repair. Adv Sci (Weinh) 2022 May;9(16):e2200050.
- Zayed M, Adair S, Dhar M. Effects of Normal Synovial Fluid and Interferon Gamma on Chondrogenic Capability and Immunomodulatory Potential Respectively on Equine Mesenchymal Stem Cells. Int J Mol Sci 2021 Jun 15;22(12).
- Son YB, Jeong YI, Jeong YW, Hossein MS, Olsson PO, Tinson A, Singh KK, Lee SY, Hwang WS. Cell Source-Dependent In Vitro Chondrogenic Differentiation Potential of Mesenchymal Stem Cell Established from Bone Marrow and Synovial Fluid of Camelus dromedarius. Animals (Basel) 2021 Jun 28;11(7).
- Li D, Gupta P, Sgaglione NA, Grande DA. Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review. J Clin Med 2021 May 7;10(9).
- Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases. Animals (Basel) 2021 Jan 19;11(1).
- Deng Z, Jin J, Wang S, Qi F, Chen X, Liu C, Li Y, Ma Y, Lyu F, Zheng Q. Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering. Ann Transl Med 2020 Dec;8(23):1598.
- Desai S, Jayasuriya CT. Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair. Bioengineering (Basel) 2020 Aug 4;7(3).
- Neybecker P, Henrionnet C, Pape E, Grossin L, Mainard D, Galois L, Loeuille D, Gillet P, Pinzano A. Respective stemness and chondrogenic potential of mesenchymal stem cells isolated from human bone marrow, synovial membrane, and synovial fluid. Stem Cell Res Ther 2020 Jul 25;11(1):316.
- Wofford A, Bow A, Newby S, Brooks S, Rodriguez R, Masi T, Stephenson S, Gotcher J, Anderson DE, Campbell J, Dhar M. Human Fat-Derived Mesenchymal Stem Cells Xenogenically Implanted in a Rat Model Show Enhanced New Bone Formation in Maxillary Alveolar Tooth Defects. Stem Cells Int 2020;2020:8142938.
- Sun Y, Wang C, Gong C. Repairing effects of glucosamine sulfate in combination with etoricoxib on articular cartilages of patients with knee osteoarthritis. J Orthop Surg Res 2020 Apr 16;15(1):150.
- To K, Zhang B, Romain K, Mak C, Khan W. Synovium-Derived Mesenchymal Stem Cell Transplantation in Cartilage Regeneration: A PRISMA Review of in vivo Studies. Front Bioeng Biotechnol 2019;7:314.
- Neybecker P, Henrionnet C, Pape E, Mainard D, Galois L, Loeuille D, Gillet P, Pinzano A. In vitro and in vivo potentialities for cartilage repair from human advanced knee osteoarthritis synovial fluid-derived mesenchymal stem cells. Stem Cell Res Ther 2018 Nov 28;9(1):329.
- Aeri A, Gorla M, Sharma GT. Veterinary Regenerative Medicine: The Evolving Role of Stem Cell-Based Therapies. Stem Cell Rev Rep 2025 Nov;21(8):2484-2510.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists