Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source.
Abstract: Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proliferation through different mechanisms. To test our hypotheses, we inhibited interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) to determine their impact on stimulated T cell proliferation. We also determined how equine MSCs modulate lymphocyte proliferation either via cell cycle arrest or apoptosis. Inhibition of IL-6 or NO did not reverse the immunomodulatory effect of MSCs on activated T cells. In contrast, inhibition of PGE2 restored T cell proliferation, restored the secretion of tumor necrosis factor-α and interferon-γ, and increased IL-10 levels. MSCs from solid-tissue-derived sources, AT and CT, inhibited T cell proliferation through induction of lymphocyte apoptosis while blood-derived MSCs, BM and CB, induced lymphocyte cell cycle arrest. Equine MSCs from different tissue sources modulated immune cell function by both overlapping and unique mechanisms. MSC tissue source may determine immunomodulatory properties of MSCs and may have very practical implications for MSC selection in the application of MSC therapy.
Publication Date: 2014-03-04 PubMed ID: 24438346DOI: 10.1089/scd.2013.0537Google 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
- 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.
The research investigates the impact of Mesenchymal stem cells (MSCs) from different tissue sources on T cell proliferation. The study shows that these stem cells intefere with T cell growth through various mechanisms depending on their tissue source.
Overview of the Research
- The research revolves around Mesenchymal stem cells (MSCs) and their role in modulating inflammation in both human and veterinary diseases.
- Mesenchymal stem cells’ origins can be traced back to different sources including bone marrow, adipose tissue, cord blood and umbilical cord tissue.
- The objective of the research was to draw a clearer understanding of how MSCs impact the proliferation of T cells, which are crucial for the immune response in the body.
- Researchers also ventured to study how MSCs taken from different origins impact T cell proliferation mechanisms.
Methodology and Findings
- To validate the hypotheses, the researchers inhibited interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) to see their effects on T cell proliferation.
- It was found that the inhibition of IL-6 or NO did not reverse the effect of MSC’s on activated T cells. In contrast, PGE2 inhibition aided in restoring the T cell proliferation.
- The research also investigated how MSCs work to modulate lymphocyte proliferation—whether through cell cycle arrest or apoptosis.
- Results showed that MSCs obtained from solid tissues (adipose tissue and umbilical cord tissue) inhibited T cell growth through inducing lymphocyte apoptosis, while MSCs derived from blood (bone marrow and cord blood) caused a halt or delay in the cell cycle of lymphocytes.
Conclusions and Implications
- The research concludes that equine MSCs obtained from different tissue sources interfere with immune cell function through both overlapping and distinct mechanisms.
- This discovery that MSCs’ tissue source might determine their immunomodulatory properties has profound implications for choosing suitable MSCs for MSC therapy applications.
- The tissue source of the MSCs might influence the therapeutic effect and success rate of MSC therapy. Thus, choosing the right MSC source is crucial to leverage its healing properties effectively.
Cite This Article
APA
Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL.
(2014).
Equine mesenchymal stem cells inhibit T cell proliferation through different mechanisms depending on tissue source.
Stem Cells Dev, 23(11), 1258-1265.
https://doi.org/10.1089/scd.2013.0537 Publication
Researcher Affiliations
- 1 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California , Davis, California.
MeSH Terms
- Adipose Tissue / cytology
- Adipose Tissue / physiology
- Animals
- Bone Marrow Cells / cytology
- Bone Marrow Cells / physiology
- Cell Proliferation / drug effects
- Cell Separation / methods
- Coculture Techniques
- Fetal Blood / cytology
- Fetal Blood / physiology
- Horses
- Interleukin-6 / metabolism
- Interleukin-6 / pharmacology
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / physiology
- Nitric Oxide / metabolism
- Nitric Oxide / pharmacology
- Signal Transduction
- T-Lymphocytes / cytology
- T-Lymphocytes / drug effects
- T-Lymphocytes / physiology
Citations
This article has been cited 47 times.- 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.
- Jammes M, Contentin R, Cassé F, Galéra P. Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies.. Front Vet Sci 2023;10:1115774.
- Cequier A, Vázquez FJ, Romero A, Vitoria A, Bernad E, García-Martínez M, Gascón 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.
- Koch DW, Schnabel LV, Ellis IM, Bates RE, Berglund AK. TGF-β2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing.. Stem Cell Res Ther 2022 Sep 16;13(1):477.
- Koch DW, Berglund AK, Messenger KM, Gilbertie JM, Ellis IM, Schnabel LV. Interleukin-1β in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells.. Front Vet Sci 2022;9:963759.
- Rahman G, Frazier TP, Gimble JM, Mohiuddin OA. The Emerging Use of ASC/Scaffold Composites for the Regeneration of Osteochondral Defects.. Front Bioeng Biotechnol 2022;10:893992.
- Chu M, Wang H, Bian L, Huang J, Wu D, Zhang R, Fei F, Chen Y, Xia J. Nebulization Therapy with Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes for COVID-19 Pneumonia.. Stem Cell Rev Rep 2022 Aug;18(6):2152-2163.
- 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).
- Uberti B, Plaza A, Henríquez C. Pre-conditioning Strategies for Mesenchymal Stromal/Stem Cells in Inflammatory Conditions of Livestock Species.. Front Vet Sci 2022;9:806069.
- Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W. Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses.. Animals (Basel) 2021 Nov 13;11(11).
- Li C, Mills Z, Zheng Z. Novel cell sources for bone regeneration.. MedComm (2020) 2021 Jun;2(2):145-174.
- Yeo GEC, Ng MH, Nordin FB, Law JX. Potential of Mesenchymal Stem Cells in the Rejuvenation of the Aging Immune System.. Int J Mol Sci 2021 May 27;22(11).
- Cequier A, Sanz C, Rodellar C, Barrachina L. The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses.. Animals (Basel) 2021 Mar 25;11(4).
- Tang WY, Liu JH, Peng CJ, Liao Y, Luo JS, Sun X, Tang YL, Luo XQ. Functional Characteristics and Application of Mesenchymal Stem Cells in Systemic Lupus Erythematosus.. Arch Immunol Ther Exp (Warsz) 2021 Mar 13;69(1):7.
- Berglund AK, Long JM, Robertson JB, Schnabel LV. TGF-β2 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.
- Bukowska J, Szóstek-Mioduchowska AZ, Kopcewicz M, Walendzik K, Machcińska S, Gawrońska-Kozak B. Adipose-Derived Stromal/Stem Cells from Large Animal Models: from Basic to Applied Science.. Stem Cell Rev Rep 2021 Jun;17(3):719-738.
- Velloso Alvarez A, Boone LH, Pondugula SR, Caldwell F, Wooldridge AA. Effects of Autologous Conditioned Serum, Autologous Protein Solution, and Triamcinolone on Inflammatory and Catabolic Gene Expression in Equine Cartilage and Synovial Explants Treated With IL-1β in Co-culture.. Front Vet Sci 2020;7:323.
- Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B, Morán G, Plaza A, Henríquez C. Pre-conditioning of Equine Bone Marrow-Derived Mesenchymal Stromal Cells Increases Their Immunomodulatory Capacity.. Front Vet Sci 2020;7:318.
- Almeida-Porada G, Atala AJ, Porada CD. Therapeutic Mesenchymal Stromal Cells for Immunotherapy and for Gene and Drug Delivery.. Mol Ther Methods Clin Dev 2020 Mar 13;16:204-224.
- MacDonald ES, Barrett JG. The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.. Front Vet Sci 2019;6:507.
- Al Naem M, Bourebaba L, Kucharczyk K, Röcken 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.
- Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ, Borjesson DL. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.. Vet Ophthalmol 2020 Jan;23(1):160-170.
- Hillmann A, Paebst F, Brehm W, Piehler D, Schubert S, Tárnok A, Burk J. A novel direct co-culture assay analyzed by multicolor flow cytometry reveals context- and cell type-specific immunomodulatory effects of equine mesenchymal stromal cells.. PLoS One 2019;14(6):e0218949.
- Taechangam N, Iyer SS, Walker NJ, Arzi B, Borjesson DL. Mechanisms utilized by feline adipose-derived mesenchymal stem cells to inhibit T lymphocyte proliferation.. Stem Cell Res Ther 2019 Jun 25;10(1):188.
- Yuan X, Logan TM, Ma T. Metabolism in Human Mesenchymal Stromal Cells: A Missing Link Between hMSC Biomanufacturing and Therapy?. Front Immunol 2019;10:977.
- Endrinaldi E, Darwin E, Zubir N, Revilla G. The Effect of Mesenchymal Stem Cell Wharton's Jelly on ADAMTS-4 and iNOS Levels in Osteoarthritis Rat Model.. Open Access Maced J Med Sci 2019 Apr 30;7(8):1270-1275.
- Philipp D, Suhr L, Wahlers T, Choi YH, Paunel-Görgülü A. Preconditioning of bone marrow-derived mesenchymal stem cells highly strengthens their potential to promote IL-6-dependent M2b polarization.. Stem Cell Res Ther 2018 Oct 25;9(1):286.
- Zhou K, Feng B, Wang W, Jiang Y, Zhang W, Zhou G, Jiang T, Cao Y, Liu W. Nanoscaled and microscaled parallel topography promotes tenogenic differentiation of ASC and neotendon formation in vitro.. Int J Nanomedicine 2018;13:3867-3881.
- Ayala-Cuellar AP, Kang JH, Jeung EB, Choi KC. Roles of Mesenchymal Stem Cells in Tissue Regeneration and Immunomodulation.. Biomol Ther (Seoul) 2019 Jan 1;27(1):25-33.
- Song WJ, Li Q, Ryu MO, Ahn JO, Bhang DH, Jung YC, Youn HY. TSG-6 released from intraperitoneally injected canine adipose tissue-derived mesenchymal stem cells ameliorate inflammatory bowel disease by inducing M2 macrophage switch in mice.. Stem Cell Res Ther 2018 Apr 6;9(1):91.
- White JL, Walker NJ, Hu JC, Borjesson DL, Athanasiou KA. A Comparison of Bone Marrow and Cord Blood Mesenchymal Stem Cells for Cartilage Self-Assembly.. Tissue Eng Part A 2018 Aug;24(15-16):1262-1272.
- Kay AG, Long G, Tyler G, Stefan A, Broadfoot SJ, Piccinini AM, Middleton J, Kehoe O. Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis.. Sci Rep 2017 Dec 21;7(1):18019.
- Reesink HL, Sutton RM, Shurer CR, Peterson RP, Tan JS, Su J, Paszek MJ, Nixon AJ. Galectin-1 and galectin-3 expression in equine mesenchymal stromal cells (MSCs), synovial fibroblasts and chondrocytes, and the effect of inflammation on MSC motility.. Stem Cell Res Ther 2017 Nov 2;8(1):243.
- Ceusters J, Lejeune JP, Sandersen C, Niesten A, Lagneaux L, Serteyn D. From skeletal muscle to stem cells: an innovative and minimally-invasive process for multiple species.. Sci Rep 2017 Apr 6;7(1):696.
- Clark KC, Fierro FA, Ko EM, Walker NJ, Arzi B, Tepper CG, Dahlenburg H, Cicchetto A, Kol A, Marsh L, Murphy WJ, Fazel N, Borjesson DL. Human and feline adipose-derived mesenchymal stem cells have comparable phenotype, immunomodulatory functions, and transcriptome.. Stem Cell Res Ther 2017 Mar 20;8(1):69.
- Chow L, Johnson V, Coy J, Regan D, Dow S. Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells.. Stem Cells Dev 2017 Mar 1;26(5):374-389.
- Huang Z, Godkin O, Schulze-Tanzil G. The Challenge in Using Mesenchymal Stromal Cells for Recellularization of Decellularized Cartilage.. Stem Cell Rev Rep 2017 Feb;13(1):50-67.
- Ishikawa S, Horinouchi C, Murata D, Matsuzaki S, Misumi K, Iwamoto Y, Korosue K, Hobo S. Isolation and characterization of equine dental pulp stem cells derived from Thoroughbred wolf teeth.. J Vet Med Sci 2017 Jan 20;79(1):47-51.
- Bavin EP, Smith O, Baird AE, Smith LC, Guest DJ. Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells.. Front Vet Sci 2015;2:55.
- Clark KC, Kol A, Shahbenderian S, Granick JL, Walker NJ, Borjesson DL. Canine and Equine Mesenchymal Stem Cells Grown in Serum Free Media Have Altered Immunophenotype.. Stem Cell Rev Rep 2016 Apr;12(2):245-56.
- Ravanidis S, Bogie JF, Donders R, Craeye D, Mays RW, Deans R, Gijbels K, Bronckaers A, Stinissen P, Pinxteren J, Hellings N. Neuroinflammatory signals enhance the immunomodulatory and neuroprotective properties of multipotent adult progenitor cells.. Stem Cell Res Ther 2015 Sep 16;6(1):176.
- Gornostaeva A, Andreeva E, Buravkova L. Factors governing the immunosuppressive effects of multipotent mesenchymal stromal cells in vitro.. Cytotechnology 2016 Aug;68(4):565-77.
- 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.
- Cheng PP, Liu XC, Ma PF, Gao C, Li JL, Lin YY, Shao W, Han S, Zhao B, Wang LM, Fu JZ, Meng LX, Li Q, Lian QZ, Xia JJ, Qi ZQ. iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation.. Stem Cells Dev 2015 Aug 1;24(15):1793-804.
- Asatrian G, Pham D, Hardy WR, James AW, Peault B. Stem cell technology for bone regeneration: current status and potential applications.. Stem Cells Cloning 2015;8:39-48.
- Domev H, Milkov I, Itskovitz-Eldor J, Dar A. Immunoevasive pericytes from human pluripotent stem cells preferentially modulate induction of allogeneic regulatory T cells.. Stem Cells Transl Med 2014 Oct;3(10):1169-81.
- 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.
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