Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro.
Abstract: The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods: MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n=10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured through P8; cells from each passage (P2 to P8) were cryopreserved until used. Immunophenotyping of MHC class I and II, CD44, CD29, CD90, LFA-1, and CD45RB was performed by using flow cytometry. Tri-lineage differentiation assays were performed to confirm MSC multipotency. Recombinant equine IFN-γ was used to stimulate MHC class II negative MSCs in culture, after which expression of MHC class II was re-examined. To assess the ability of MHC class II negative or positive MSCs to stimulate an immune response, modified one-way mixed leukocyte reactions (MLRs) were performed by using MHC-matched and mismatched responder PBLs and stimulator PBLs or MSCs. Proliferation of gated CFSE-labeled CD3+ responder T cells was evaluated via CFSE attenuation by using flow cytometry and reported as the number of cells in the proliferating T-cell gate. Results: MSCs varied widely in MHC class II expression despite being homogenous in terms of "stemness" marker expression and ability to undergo trilineage differentiation. Stimulation of MHC class II negative MSCs with IFN-γ resulted in markedly increased expression of MHC class II. MLR results revealed that MHC-mismatched MHC class II-positive MSCs caused significantly increased responder T-cell proliferation compared with MHC-mismatched MHC class II-negative and MHC-matched MSCs, and equivalent to that of the positive control of MHC-mismatched leukocytes. Conclusions: The results of this study suggest that MSCs should be confirmed as MHC class II negative before allogeneic application. Additionally, it must be considered that even MHC class II-negative MSCs could upregulate MHC class II expression if implanted into an area of active inflammation, as demonstrated with in vitro stimulation with IFN-γ.
Publication Date: 2014-01-24 PubMed ID: 24461709PubMed Central: PMC4055004DOI: 10.1186/scrt402Google 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
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
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 explores how horse mesenchymal stromal cells (MSCs), used in regenerative treatments, can incite an immune response. The team examined if variations in major histocompatibility complex (MHC) class II expression might be the cause and concluded that only MSCs confirmed as MHC class II negative should be used in treatment.
Research Objectives and Methodology
- The aim of this study was two-fold: Firstly, to immunophenotype MSCs from horses whose MHC haplotype was known and, secondly, to compare the immunogenicity of MSCs with varying MHC class II expression.
- MSCs and peripheral blood leukocytes (PBLs) were collected and cultured from ten thoroughbred horses, and cells from each passage stage were preserved for analysis.
- The team used flow cytometry to immunophenotype crucial markers: MHC class I and II, CD44, CD29, CD90, LFA-1, and CD45RB.
- To confirm the multipotency of the MSCs, tri-lineage differentiation assays were performed.
- The researchers used recombinant equine IFN-γ to stimulate MHC class II negative MSCs in culture. Once stimulated, the MHC class II expression was evaluated again.
- Lastly, to assess the ability of MHC class II negative or positive MSCs to stimulate an immune response, modified one-way mixed leukocyte reactions (MLRs) were performed.
Results of the Research
- Despite the MSCs being homogeneous in terms of “stemness” marker expression, the study found significant variations in MHC class II expression.
- Stimulation of MHC class II negative MSCs with IFN-γ resulted in a significant increase in MHC class II expression.
- MLR results highlighted that MHC class II-positive MSCs, when MHC-mismatched, caused an increased T-cell response compared to MHC class II-negative and MHC-matched MSCs. The response was similar to the positive control of MHC-mismatched leukocytes.
Conclusions of the Research
- The research concludes that for allogeneic applications, only MSCs confirmed as MHC class II negative should be used.
- The researchers also warn that even MHC class II-negative MSCs could potentially upregulate MHC class II expression if implanted into a region with active inflammation. This conclusion was based on the in-vitro stimulation with IFN-γ.
Cite This Article
APA
Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA.
(2014).
Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro.
Stem Cell Res Ther, 5(1), 13.
https://doi.org/10.1186/scrt402 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Cells, Cultured
- Genes, MHC Class II / genetics
- Genes, MHC Class II / immunology
- Horses
- Immunophenotyping
- Interferon-gamma / pharmacology
- Leukocytes / immunology
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / drug effects
- Mesenchymal Stem Cells / immunology
Grant Funding
- K08 AR060875 / NIAMS NIH HHS
- 1K08AR060875-01A1 / NIAMS NIH HHS
- S10RR023781 / NCRR NIH HHS
References
This article includes 41 references
- Griffin MD, Ryan AE, Alagesan S, Lohan P, Treacy O, Ritter T. Anti-donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far?. Immunol Cell Biol 2013 Jan;91(1):40-51.
- Stagg J, Galipeau J. Immune plasticity of bone marrow-derived mesenchymal stromal cells.. Handb Exp Pharmacol 2007;(180):45-66.
- Stagg J. Immune regulation by mesenchymal stem cells: two sides to the coin.. Tissue Antigens 2007 Jan;69(1):1-9.
- Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies.. Hum Gene Ther 2010 Dec;21(12):1641-55.
- Eliopoulos N, Stagg J, Lejeune L, Pommey S, Galipeau J. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice.. Blood 2005 Dec 15;106(13):4057-65.
- Potian JA, Aviv H, Ponzio NM, Harrison JS, Rameshwar P. Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens.. J Immunol 2003 Oct 1;171(7):3426-34.
- Zangi L, Margalit R, Reich-Zeliger S, Bachar-Lustig E, Beilhack A, Negrin R, Reisner Y. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells.. Stem Cells 2009 Nov;27(11):2865-74.
- Badillo AT, Beggs KJ, Javazon EH, Tebbets JC, Flake AW. Murine bone marrow stromal progenitor cells elicit an in vivo cellular and humoral alloimmune response.. Biol Blood Marrow Transplant 2007 Apr;13(4):412-22.
- Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting.. Blood 2006 Sep 15;108(6):2114-20.
- Jones EA, Kinsey SE, English A, Jones RA, Straszynski L, Meredith DM, Markham AF, Jack A, Emery P, McGonagle D. Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells.. Arthritis Rheum 2002 Dec;46(12):3349-60.
- Fortier LA. Making progress in the what, when and where of regenerative medicine for our equine patients.. Equine Vet J 2012 Sep;44(5):511-2.
- Fortier LA, Travis AJ. Stem cells in veterinary medicine.. Stem Cell Res Ther 2011 Feb 23;2(1):9.
- Frisbie DD, Smith RK. Clinical update on the use of mesenchymal stem cells in equine orthopaedics.. Equine Vet J 2010 Jan;42(1):86-9.
- Frisbie DD, Stewart MC. Cell-based therapies for equine joint disease.. Vet Clin North Am Equine Pract 2011 Aug;27(2):335-49.
- Schnabel LV, Fortier LA, McIlwraith CW, Nobert KM. Therapeutic use of stem cells in horses: which type, how, and when?. Vet J 2013 Sep;197(3):570-7.
- De Schauwer C, Van de Walle GR, Van Soom A, Meyer E. Mesenchymal stem cell therapy in horses: useful beyond orthopedic injuries?. Vet Q 2013 Dec;33(4):234-41.
- Guest DJ, Ousey JC, Smith MR. Defining the expression of marker genes in equine mesenchymal stromal cells.. Stem Cells Cloning 2008;1:1-9.
- De Schauwer C, Meyer E, Van de Walle GR, Van Soom A. Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.. Theriogenology 2011 May;75(8):1431-43.
- Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL. Comparative Analysis of the Immunomodulatory Properties of Equine Adult-Derived Mesenchymal Stem Cells().. Cell Med 2012;4(1):1-11.
- Guest DJ, Smith MR, Allen WR. Monitoring the fate of autologous and allogeneic mesenchymal progenitor cells injected into the superficial digital flexor tendon of horses: preliminary study.. Equine Vet J 2008 Mar;40(2):178-81.
- Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ. Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons.. J Orthop Res 2009 Oct;27(10):1392-8.
- Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK. Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon.. Equine Vet J 2012 Jan;44(1):25-32.
- Wilke MM, Nydam DV, Nixon AJ. Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model.. J Orthop Res 2007 Jul;25(7):913-25.
- Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, Major MD, Schneider RK, Zubrod CJ, Kawcak CE, Goodrich LR. Clinical outcome after intra-articular administration of bone marrow derived mesenchymal stem cells in 33 horses with stifle injury.. Vet Surg 2014 Mar;43(3):255-65.
- Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis.. J Orthop Res 2009 Dec;27(12):1675-80.
- McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM, Kawcak CE, Steadman JR. Evaluation of intra-articular mesenchymal stem cells to augment healing of microfractured chondral defects.. Arthroscopy 2011 Nov;27(11):1552-61.
- Lazary S, Antczak DF, Bailey E, Bell TK, Bernoco D, Byrns G, McClure JJ. Joint Report of the Fifth International Workshop on Lymphocyte Alloantigens of the Horse, Baton Rouge, Louisiana, 31 October-1 November 1987.. Anim Genet 1988;19(4):447-56.
- Tallmadge RL, Campbell JA, Miller DC, Antczak DF. Analysis of MHC class I genes across horse MHC haplotypes.. Immunogenetics 2010 Mar;62(3):159-72.
- Tallmadge RL, Lear TL, Antczak DF. Genomic characterization of MHC class I genes of the horse.. Immunogenetics 2005 Nov;57(10):763-74.
- Tseng CT, Miller D, Cassano J, Bailey E, Antczak DF. Identification of equine major histocompatibility complex haplotypes using polymorphic microsatellites.. Anim Genet 2010 Dec;41 Suppl 2(Suppl 2):150-3.
- Flaminio MJ, Antczak DF. Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response.. Placenta 2005 Feb-Mar;26(2-3):148-59.
- Radcliffe CH, Flaminio MJ, Fortier LA. Temporal analysis of equine bone marrow aspirate during establishment of putative mesenchymal progenitor cell populations.. Stem Cells Dev 2010 Feb;19(2):269-82.
- Watts AE, Ackerman-Yost JC, Nixon AJ. A comparison of three-dimensional culture systems to evaluate in vitro chondrogenesis of equine bone marrow-derived mesenchymal stem cells.. Tissue Eng Part A 2013 Oct;19(19-20):2275-83.
- Chan WK, Lau AS, Li JC, Law HK, Lau YL, Chan GC. MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge.. Exp Hematol 2008 Nov;36(11):1545-55.
- Romieu-Mourez R, Franu00e7ois M, Boivin MN, Stagg J, Galipeau J. Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density.. J Immunol 2007 Aug 1;179(3):1549-58.
- Crovace A, Lacitignola L, De Siena R, Rossi G, Francioso E. Cell therapy for tendon repair in horses: an experimental study.. Vet Res Commun 2007 Aug;31 Suppl 1:281-3.
- Crovace A, Lacitignola L, Rossi G, Francioso E. Histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase-induced tendinitis of equine superficial digital flexor tendon.. Vet Med Int 2010;2010:250978.
- Antczak DF, Bailey E, Barger B, Guerin G, Lazary S, McClure J, Mottironi VD, Symons R, Templeton J, Varewyck H. Joint report of the Third International Workshop on Lymphocyte Alloantigens of the Horse, Kennett Square, Pennsylvania, 25-27 April 1984.. Anim Genet 1986;17(4):363-73.
- Delling U, Lindner K, Ribitsch I, Ju00fclke H, Brehm W. Comparison of bone marrow aspiration at the sternum and the tuber coxae in middle-aged horses.. Can J Vet Res 2012 Jan;76(1):52-6.
- Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion.. Stem Cells 2004;22(5):675-82.
- Majors AK, Boehm CA, Nitto H, Midura RJ, Muschler GF. Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation.. J Orthop Res 1997 Jul;15(4):546-57.
Citations
This article has been cited 62 times.- Jammes M, Cassu00e9 F, Velot E, Bianchi A, Audigiu00e9 F, Contentin R, Galu00e9ra P. Pro-Inflammatory Cytokine Priming and Purification Method Modulate the Impact of Exosomes Derived from Equine Bone Marrow Mesenchymal Stromal Cells on Equine Articular Chondrocytes.. Int J Mol Sci 2023 Sep 16;24(18).
- Heilen LB, Rou00dfgardt J, Dern-Wieloch J, Vogelsberg J, Staszyk C. Isolation and cultivation as well as in situ identification of MSCs from equine dental pulp and periodontal ligament.. Front Vet Sci 2023;10:1116671.
- Pezzanite LM, Chow L, Griffenhagen GM, Bass L, Goodrich LR, Impastato R, Dow S. Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system.. Front Vet Sci 2023;10:1109473.
- Jammes M, Contentin R, Cassu00e9 F, Galu00e9ra P. Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies.. Front Vet Sci 2023;10:1115774.
- Keller LE, Tait Wojno ED, Begum L, Fortier LA. Regulatory T cells provide chondroprotection through increased TIMP1, IL-10 and IL-4, but cannot mitigate the catabolic effects of IL-1u03b2 and IL-6 in a tri-culture model of osteoarthritis.. Osteoarthr Cartil Open 2021 Sep;3(3):100193.
- Pezzanite LM, Chow L, Phillips J, Griffenhagen GM, Moore AR, Schaer TP, Engiles JB, Werpy N, Gilbertie J, Schnabel LV, Antczak D, Miller D, Dow S, Goodrich LR. TLR-activated mesenchymal stromal cell therapy and antibiotics to treat multi-drug resistant Staphylococcal septic arthritis in an equine model.. Ann Transl Med 2022 Nov;10(21):1157.
- Cequier A, Vu00e1zquez FJ, Romero A, Vitoria A, Bernad E, Garcu00eda-Martu00ednez M, Gascu00f3n I, Barrachina L, Rodellar C. The immunomodulation-immunogenicity balance of equine Mesenchymal Stem Cells (MSCs) is differentially affected by the immune cell response depending on inflammatory licensing and major histocompatibility complex (MHC) compatibility.. Front Vet Sci 2022;9:957153.
- Keller LE, Tait Wojno ED, Begum L, Fortier LA. Interleukin-6 neutralization and regulatory T cells are additive in chondroprotection from IL-1u03b2-induced inflammation.. J Orthop Res 2023 May;41(5):942-950.
- Even KM, Gaesser AM, Ciamillo SA, Linardi RL, Ortved KF. Comparing the immunomodulatory properties of equine BM-MSCs culture expanded in autologous platelet lysate, pooled platelet lysate, equine serum and fetal bovine serum supplemented culture media.. Front Vet Sci 2022;9:958724.
- Koch DW, Berglund AK, Messenger KM, Gilbertie JM, Ellis IM, Schnabel LV. Interleukin-1u03b2 in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells.. Front Vet Sci 2022;9:963759.
- Zhu Y, Fu W. Peripheral Blood-Derived Stem Cells for the Treatment of Cartilage Injuries: A Systematic Review.. Front Bioeng Biotechnol 2022;10:956614.
- Rosa GDS, Krieck AMT, Padula ET, Stievani FC, Rossi MC, Pfeifer JPH, Basso RM, Braz AMM, Golim MA, Alves ALG. Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration.. Front Immunol 2022;13:871216.
- Prajwal GS, Jeyaraman N, Kanth V K, Jeyaraman M, Muthu S, Rajendran SNS, Rajendran RL, Khanna M, Oh EJ, Choi KY, Chung HY, Ahn BC, Gangadaran P. Lineage Differentiation Potential of Different Sources of Mesenchymal Stem Cells for Osteoarthritis Knee.. Pharmaceuticals (Basel) 2022 Mar 22;15(4).
- Cequier A, Romero A, Vu00e1zquez 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.
- Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW. Immune response to allogeneic equine mesenchymal stromal cells.. Stem Cell Res Ther 2021 Nov 12;12(1):570.
- Rowland AL, Burns ME, Levine GJ, Watts AE. Preparation Technique Affects Recipient Immune Targeting of Autologous Mesenchymal Stem Cells.. Front Vet Sci 2021;8:724041.
- 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).
- Berglund AK, Long JM, Robertson JB, Schnabel LV. TGF-u03b22 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties.. Front Cell Dev Biol 2021;9:628382.
- Kamm JL, Riley CB, Parlane N, Gee EK, McIlwraith CW. Interactions Between Allogeneic Mesenchymal Stromal Cells and the Recipient Immune System: A Comparative Review With Relevance to Equine Outcomes.. Front Vet Sci 2020;7:617647.
- Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
- Becktell L, Matuska AM, Hon S, Delco ML, Cole BJ, Begum L, Zhang S, Fortier LA. Proteomic Analysis and Cell Viability of Nine Amnion, Chorion, Umbilical Cord, and Amniotic Fluid-Derived Products.. Cartilage 2021 Dec;13(2_suppl):495S-507S.
- Voga M, Adamic N, Vengust M, Majdic G. Stem Cells in Veterinary Medicine-Current State and Treatment Options.. Front Vet Sci 2020;7:278.
- MacDonald ES, Barrett JG. The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.. Front Vet Sci 2019;6:507.
- Barrachina L, Cequier A, Romero A, Vitoria A, Zaragoza P, Vu00e1zquez FJ, Rodellar C. Allo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility.. Stem Cell Res Ther 2020 Feb 7;11(1):52.
- Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. Single and repeated intra-articular injections in the tarsocrural joint with allogeneic and autologous equine bone marrow-derived mesenchymal stem cells are safe, but did not reduce acute inflammation in an experimental interleukin-1u03b2 model of synovitis.. Equine Vet J 2020 Jul;52(4):601-612.
- Al Naem M, Bourebaba L, Kucharczyk K, Ru00f6cken M, Marycz K. Therapeutic mesenchymal stromal stem cells: Isolation, characterization and role in equine regenerative medicine and metabolic disorders.. Stem Cell Rev Rep 2020 Apr;16(2):301-322.
- Kamm JL, Parlane NA, Riley CB, Gee EK, Dittmer KE, McIlwraith CW. Blood type and breed-associated differences in cell marker expression on equine bone marrow-derived mesenchymal stem cells including major histocompatibility complex class II antigen expression.. PLoS One 2019;14(11):e0225161.
- Gugjoo MB, Fazili MR, Gayas MA, Ahmad RA, Dhama K. Animal mesenchymal stem cell research in cartilage regenerative medicine - a review.. Vet Q 2019 Dec;39(1):95-120.
- Gale AL, Linardi RL, McClung G, Mammone RM, Ortved KF. Comparison of the Chondrogenic Differentiation Potential of Equine Synovial Membrane-Derived and Bone Marrow-Derived Mesenchymal Stem Cells.. Front Vet Sci 2019;6:178.
- Gale AL, Mammone RM, Dodson ME, Linardi RL, Ortved KF. The effect of hypoxia on chondrogenesis of equine synovial membrane-derived and bone marrow-derived mesenchymal stem cells.. BMC Vet Res 2019 Jun 14;15(1):201.
- Bertoni L, Branly T, Jacquet S, Desancu00e9 M, Desquilbet L, Rivory P, Hartmann DJ, Denoix JM, Audigiu00e9 F, Galu00e9ra P, Demoor M. Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses.. Stem Cells Int 2019;2019:9431894.
- Bochon B, Kozubska M, Surygau0142a G, Witkowska A, Kuu017aniewicz R, Grzeszczak W, Wystrychowski G. Mesenchymal Stem Cells-Potential Applications in Kidney Diseases.. Int J Mol Sci 2019 May 18;20(10).
- He B, Chen J, Liu L, Wang H, Wang S, Li P, Zhou J. Knockdown of Tcf3 enhances the wound healing effect of bone marrow mesenchymal stem cells in rats.. Biosci Rep 2019 Aug 30;39(8).
- Broeckx SY, Martens AM, Bertone AL, Van Brantegem L, Duchateau L, Van Hecke L, Dumoulin M, Oosterlinck M, Chiers K, Hussein H, Pille F, Spaas JH. The use of equine chondrogenic-induced mesenchymal stem cells as a treatment for osteoarthritis: A randomised, double-blinded, placebo-controlled proof-of-concept study.. Equine Vet J 2019 Nov;51(6):787-794.
- Cabon Q, Febre M, Gomez N, Cachon T, Pillard P, Carozzo C, Saulnier N, Robert C, Livet V, Rakic R, Plantier N, Saas P, Maddens S, Viguier E. Long-Term Safety and Efficacy of Single or Repeated Intra-Articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells for Managing Pain and Lameness in Moderate to Severe Canine Osteoarthritis Without Anti-inflammatory Pharmacological Support: Pilot Clinical Study.. Front Vet Sci 2019;6:10.
- Broeckx SY, Seys B, Suls M, Vandenberghe A, Mariu00ebn T, Adriaensen E, Declercq J, Van Hecke L, Braun G, Hellmann K, Spaas JH. Equine Allogeneic Chondrogenic Induced Mesenchymal Stem Cells Are an Effective Treatment for Degenerative Joint Disease in Horses.. Stem Cells Dev 2019 Mar 15;28(6):410-422.
- Ball AN, Phillips JN, McIlwraith CW, Kawcak CE, Samulski RJ, Goodrich LR. Genetic modification of scAAV-equine-BMP-2 transduced bone-marrow-derived mesenchymal stem cells before and after cryopreservation: An "off-the-shelf" option for fracture repair.. J Orthop Res 2019 Jun;37(6):1310-1317.
- Grady ST, Britton L, Hinrichs K, Nixon AJ, Watts AE. Persistence of fluorescent nanoparticle-labelled bone marrow mesenchymal stem cells in vitro and after intra-articular injection.. J Tissue Eng Regen Med 2019 Feb;13(2):191-202.
- Grady ST, Watts AE, Thompson JA, Penedo MCT, Konganti K, Hinrichs K. Effect of intra-ovarian injection of mesenchymal stem cells in aged mares.. J Assist Reprod Genet 2019 Mar;36(3):543-556.
- Rowland AL, Xu JJ, Joswig AJ, Gregory CA, Antczak DF, Cummings KJ, Watts AE. In vitro MSC function is related to clinical reaction in vivo.. Stem Cell Res Ther 2018 Nov 8;9(1):295.
- Bogers SH. Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know.. Front Vet Sci 2018;5:70.
- Cassano JM, Schnabel LV, Goodale MB, Fortier LA. Inflammatory licensed equine MSCs are chondroprotective and exhibit enhanced immunomodulation in an inflammatory environment.. Stem Cell Res Ther 2018 Apr 3;9(1):82.
- Holmes HL, Wilson B, Goerger JP, Silverberg JL, Cohen I, Zipfel WR, Fortier LA. Facilitated recruitment of mesenchymal stromal cells by bone marrow concentrate and platelet rich plasma.. PLoS One 2018;13(3):e0194567.
- Berglund AK, Fortier LA, Antczak DF, Schnabel LV. Immunoprivileged no more: measuring the immunogenicity of allogeneic adult mesenchymal stem cells.. Stem Cell Res Ther 2017 Dec 22;8(1):288.
- Ishikawa S, Horinouchi C, Mizoguchi R, Senokuchi A, Kamikakimoto R, Murata D, Hatazoe T, Tozaki T, Misumi K, Hobo S. Isolation of equine peripheral blood stem cells from a Japanese native horse.. J Equine Sci 2017;28(4):153-158.
- Lohan P, Treacy O, Griffin MD, Ritter T, Ryan AE. Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?. Front Immunol 2017;8:1626.
- Berglund AK, Fisher MB, Cameron KA, Poole EJ, Schnabel LV. Transforming Growth Factor-u03b22 Downregulates Major Histocompatibility Complex (MHC) I and MHC II Surface Expression on Equine Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Other Phenotypic Cell Surface Markers.. Front Vet Sci 2017;4:84.
- Sherman AB, Gilger BC, Berglund AK, Schnabel LV. Effect of bone marrow-derived mesenchymal stem cells and stem cell supernatant on equine corneal wound healing in vitro.. Stem Cell Res Ther 2017 May 25;8(1):120.
- Joswig AJ, Mitchell A, Cummings KJ, Levine GJ, Gregory CA, Smith R 3rd, Watts AE. Repeated intra-articular injection of allogeneic mesenchymal stem cells causes an adverse response compared to autologous cells in the equine model.. Stem Cell Res Ther 2017 Feb 28;8(1):42.
- Berglund AK, Schnabel LV. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.. Equine Vet J 2017 Jul;49(4):539-544.
- Dias MC, Landim-Alvarenga FD, de Moraes CN, da Costa LD, Geraldini CM, de Vasconcelos Machado VM, Maia L. Intramuscular Transplantation of Allogeneic Mesenchymal Stromal Cells Derived from Equine Umbilical Cord.. Int J Stem Cells 2016 Nov 30;9(2):239-249.
- Hagmann S, Rimmele C, Bucur F, Dreher T, Zeifang F, Moradi B, Gotterbarm T. Mesenchymal Stromal Cells from Osteoarthritic Synovium Are a Distinct Population Compared to Their Bone-Marrow Counterparts regarding Surface Marker Distribution and Immunomodulation of Allogeneic CD4+ T-Cell Cultures.. Stem Cells Int 2016;2016:6579463.
- Ardanaz N, Vu00e1zquez FJ, Romero A, Remacha AR, Barrachina L, Sanz A, Ranera B, Vitoria A, Albareda J, Prades M, Zaragoza P, Martu00edn-Burriel I, Rodellar C. Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints.. BMC Vet Res 2016 Mar 31;12:65.
- Peters AE, Watts AE. Biopsy Needle Advancement during Bone Marrow Aspiration Increases Mesenchymal Stem Cell Concentration.. Front Vet Sci 2016;3:23.
- Mitchell A, Rivas KA, Smith R 3rd, Watts AE. Cryopreservation of equine mesenchymal stem cells in 95% autologous serum and 5% DMSO does not alter post-thaw growth or morphology in vitro compared to fetal bovine serum or allogeneic serum at 20 or 95% and DMSO at 10 or 5.. Stem Cell Res Ther 2015 Nov 26;6:231.
- Tessier L, Bienzle D, Williams LB, Koch TG. Phenotypic and immunomodulatory properties of equine cord blood-derived mesenchymal stromal cells.. PLoS One 2015;10(4):e0122954.
- Pezzanite LM, Fortier LA, Antczak DF, Cassano JM, Brosnahan MM, Miller D, Schnabel LV. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.. Stem Cell Res Ther 2015 Apr 12;6(1):54.
- Kol A, Wood JA, Carrade Holt DD, Gillette JA, Bohannon-Worsley LK, Puchalski SM, Walker NJ, Clark KC, Watson JL, Borjesson DL. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.. Stem Cell Res Ther 2015 Apr 15;6(1):73.
- Bussche L, Van de Walle GR. Peripheral Blood-Derived Mesenchymal Stromal Cells Promote Angiogenesis via Paracrine Stimulation of Vascular Endothelial Growth Factor Secretion in the Equine Model.. Stem Cells Transl Med 2014 Dec;3(12):1514-25.
- Paterson YZ, Rash N, Garvican ER, Paillot R, Guest DJ. Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro.. Stem Cell Res Ther 2014 Jul 30;5(4):90.
- Schnabel LV, Abratte CM, Schimenti JC, Felippe MJ, Cassano JM, Southard TL, Cross JA, Fortier LA. Induced pluripotent stem cells have similar immunogenic and more potent immunomodulatory properties compared with bone marrow-derived stromal cells in vitro.. Regen Med 2014;9(5):621-35.