Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.
Abstract: Mesenchymal stromal cells (MSC) are a very promising subpopulation of adult stem cells for cell-based regenerative therapies in veterinary medicine. Despite major progress in the knowledge on adult stem cells during recent years, a proper identification of MSC remains a challenge. In human medicine, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) recently proposed three criteria to define MSC. Firstly, cells must be plastic-adherent when maintained under standard culture conditions. Secondly, MSC must express CD73, CD90 and CD105, and lack expression of CD34, CD45, CD14 or CD11b, CD79α or CD19 and MHC class II antigens. Thirdly, MSC must be able to differentiate into osteoblasts, adipocytes and chondroblasts in vitro. Successful isolation and differentiation of equine MSC from different sources such as bone marrow, fat tissue, umbilical cord blood, Wharton's Jelly or peripheral blood has been widely reported. However, their unequivocal immunophenotyping is hampered by the lack of a single specific marker and the limited availability of monoclonal anti-horse antibodies, which are two major factors complicating successful research on equine MSC. Detection of gene expression on mRNA level is hereby a valuable alternative, although the need still exists to test several antibody clones in search for cross-reactivity. To date, commercial antibodies recognizing equine epitopes are only available for CD13, CD44 and MHC-II. Moreover, as the expression of certain adult stem cell markers may differ between species, it is mandatory to define a set of CD markers which can be uniformly applied for the identification of equine MSC.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication Date: 2010-12-31 PubMed ID: 21196039DOI: 10.1016/j.theriogenology.2010.11.008Google 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
- Review
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 article talks about the lack of identification method uniformity when it comes to equine mesenchymal stromal cells (MSC), a type of adult stem cells that have significant potential for regenerative therapies in veterinary medicine.
Understanding Mesenchymal Stromal Cells
- Mesenchymal stromal cells (MSC) are a type of adult stem cells that have a vital role in cell-based regenerative therapies, particularly in veterinary medicine.
- Despite advances in our understanding of these cells, accurately identifying them remains a challenge.
- The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy (ISCT) has recently defined three distinct criteria for defining MSC.
The Three Criteria for Defining MSC
- The first criterion stipulates that these cells should stick to plastic when preserved under standard culture parameters.
- The second one specifies that MSC must express specific markers, known as CDs (cluster of differentiation molecules), such as CD73, CD90 and CD105, but should not express CD34, CD45, CD14 or CD11b, CD79α or CD19 and MHC class II antigens.
- The third requirement points out that MSC should be capable of differentiating into several types of cells, specifically osteoblasts, adipocytes and chondroblasts in a laboratory setting.
Challenges in Equine MSC Research
- Mesenchymal stromal cells have been efficiently isolated and differentiated from different sources in horses, such as bone marrow, adipose tissue, umbilical cord blood, Wharton’s Jelly or peripheral blood.
- However, accurate identification of these cells has been complicated by the lack of a specific marker and scarce availability of monoclonal anti-horse antibodies.
- Due to the lack of appropriate antibodies, researchers resort to detecting gene expression on the mRNA level. Even then, testing must be done to find any possible cross-reactivity between the antibodies used.
Need for a Uniform Identification Method
- The study highlights the necessity for a standard set of CD markers for the identification of equine MSC as some markers may not express the same way across different species.
- Currently, commercially available antibodies that recognize equine epitopes are limited to CD13, CD44 and MHC-II.
Cite This Article
APA
De Schauwer C, Meyer E, Van de Walle GR, Van Soom A.
(2010).
Markers of stemness in equine mesenchymal stem cells: a plea for uniformity.
Theriogenology, 75(8), 1431-1443.
https://doi.org/10.1016/j.theriogenology.2010.11.008 Publication
Researcher Affiliations
- Department of Reproduction, Obstetrics and Herd Health, Ghent University, Merelbeke, Belgium. Catharina.Deschauwer@UGent.be
MeSH Terms
- Animals
- Biomarkers
- Gene Expression Regulation
- Horses / physiology
- Immunophenotyping
- Mesenchymal Stem Cells / physiology
Citations
This article has been cited 59 times.- Liu YL, Chen JS, An JH, Cai ZG, Lan JC, Li Y, Kong XW, Zhang MY, Hou R, Wang DH. Characteristics of mesenchymal stem cells and their exosomes derived from giant panda (Ailuropoda melanoleuca) endometrium. In Vitro Cell Dev Biol Anim 2023 Aug 28;.
- Phyo H, Aburza A, Mellanby K, Esteves CL. Characterization of canine adipose- and endometrium-derived Mesenchymal Stem/Stromal Cells and response to lipopolysaccharide. Front Vet Sci 2023;10:1180760.
- Salari Sedigh H, Saffarpour A, Jamshidi S, Ashouri M, Nassiri SM, Dehghan MM, Ranjbar E, Shafieian R. In vitro investigation of canine periodontal ligament-derived mesenchymal stem cells: A possibility of promising tool for periodontal regeneration. J Oral Biol Craniofac Res 2023 May-Jun;13(3):403-411.
- 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).
- Beerts C, Pauwelyn G, Depuydt E, Xu Y, Saunders JH, Peremans K, Spaas JH. Homing of radiolabelled xenogeneic equine peripheral blood-derived MSCs towards a joint lesion in a dog. Front Vet Sci 2022;9:1035175.
- Caruso M, Shuttle S, Amelse L, Elkhenany H, Schumacher J, Dhar MS. A pilot study to demonstrate the paracrine effect of equine, adult allogenic mesenchymal stem cells in vitro, with a potential for healing of experimentally-created, equine thoracic wounds in vivo. Front Vet Sci 2022;9:1011905.
- Trachsel DS, Stage HJ, Rausch S, Trappe S, Söllig K, Sponder G, Merle R, Aschenbach JR, Gehlen H. Comparison of Sources and Methods for the Isolation of Equine Adipose Tissue-Derived Stromal/Stem Cells and Preliminary Results on Their Reaction to Incubation with 5-Azacytidine. Animals (Basel) 2022 Aug 11;12(16).
- Chang PH, Lee CH, Wu TM, Yeh KY, Wang HM, Huang WK, Chan SC, Chou WC, Kuan FC, Kuo HC, Kuo YC, Hu CC, Hsieh JC. Association of early changes of circulating cancer stem-like cells with survival among patients with metastatic breast cancer. Ther Adv Med Oncol 2022;14:17588359221110182.
- Sohrabi B, Dayeri B, Zahedi E, Khoshbakht S, Nezamabadi Pour N, Ranjbar H, Davari Nejad A, Noureddini M, Alani B. Mesenchymal stem cell (MSC)-derived exosomes as novel vehicles for delivery of miRNAs in cancer therapy. Cancer Gene Ther 2022 Aug;29(8-9):1105-1116.
- Rodríguez Escobar MI, Cadena E, Nhu TT, Cooreman-Algoed M, De Smet S, Dewulf J. Analysis of the Cultured Meat Production System in Function of Its Environmental Footprint: Current Status, Gaps and Recommendations. Foods 2021 Nov 30;10(12).
- Hagen A, Lehmann H, Aurich S, Bauer N, Melzer M, Moellerberndt J, Patané V, Schnabel CL, Burk J. Scalable Production of Equine Platelet Lysate for Multipotent Mesenchymal Stromal Cell Culture. Front Bioeng Biotechnol 2020;8:613621.
- Bagge J, MacLeod JN, Berg LC. Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age. Front Vet Sci 2020;7:602403.
- Mançanares ACF, Cabezas J, Manríquez J, de Oliveira VC, Wong Alvaro YS, Rojas D, Navarrete Aguirre F, Rodriguez-Alvarez L, Castro FO. Edition of Prostaglandin E2 Receptors EP2 and EP4 by CRISPR/Cas9 Technology in Equine Adipose Mesenchymal Stem Cells. Animals (Basel) 2020 Jun 23;10(6).
- MacDonald ES, Barrett JG. The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses. Front Vet Sci 2019;6:507.
- Gugjoo MB, Hussain S, Amarpal, Shah RA, Dhama K. Mesenchymal Stem Cell-Mediated Immuno-Modulatory and Anti- Inflammatory Mechanisms in Immune and Allergic Disorders. Recent Pat Inflamm Allergy Drug Discov 2020;14(1):3-14.
- Mazzotti E, Teti G, Falconi M, Chiarini F, Barboni B, Mazzotti A, Muttini A. Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model. Cells 2019 Sep 20;8(10).
- Kamel M, Pavulraj S, Osterrieder K, Azab W. EHV-1 Pathogenesis: Current in vitro Models and Future Perspectives. Front Vet Sci 2019;6:251.
- 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.
- Pessôa LVF, Pires PRL, Del Collado M, Pieri NCG, Recchia K, Souza AF, Perecin F, da Silveira JC, de Andrade AFC, Ambrosio CE, Bressan FF, Meirelles FV. Generation and miRNA Characterization of Equine Induced Pluripotent Stem Cells Derived from Fetal and Adult Multipotent Tissues. Stem Cells Int 2019;2019:1393791.
- Zahedi M, Parham A, Dehghani H, Kazemi Mehrjerdi H. Equine bone marrow-derived mesenchymal stem cells: optimization of cell density in primary culture. Stem Cell Investig 2018;5:31.
- Bundgaard L, Stensballe A, Elbæk KJ, Berg LC. Mapping of equine mesenchymal stromal cell surface proteomes for identification of specific markers using proteomics and gene expression analysis: an in vitro cross-sectional study. Stem Cell Res Ther 2018 Oct 25;9(1):288.
- Chen G, Bracamonte-Baran W, Diny NL, Hou X, Talor MV, Fu K, Liu Y, Davogustto G, Vasquez H, Taegtmeyer H, Frazier OH, Waisman A, Conway SJ, Wan F, Čiháková D. Sca-1(+) cardiac fibroblasts promote development of heart failure. Eur J Immunol 2018 Sep;48(9):1522-1538.
- Baird A, Lindsay T, Everett A, Iyemere V, Paterson YZ, McClellan A, Henson FMD, Guest DJ. Osteoblast differentiation of equine induced pluripotent stem cells. Biol Open 2018 May 10;7(5).
- Santos VH, Pfeifer JPH, de Souza JB, Milani BHG, de Oliveira RA, Assis MG, Deffune E, Moroz A, Alves ALG. Culture of mesenchymal stem cells derived from equine synovial membrane in alginate hydrogel microcapsules. BMC Vet Res 2018 Mar 27;14(1):114.
- Naskou MC, Sumner SM, Chocallo A, Kemelmakher H, Thoresen M, Copland I, Galipeau J, Peroni JF. Platelet lysate as a novel serum-free media supplement for the culture of equine bone marrow-derived mesenchymal stem cells. Stem Cell Res Ther 2018 Mar 22;9(1):75.
- Merlo B, Teti G, Mazzotti E, Ingrà L, Salvatore V, Buzzi M, Cerqueni G, Dicarlo M, Lanci A, Castagnetti C, Iacono E. Wharton's Jelly Derived Mesenchymal Stem Cells: Comparing Human and Horse. Stem Cell Rev Rep 2018 Aug;14(4):574-584.
- Duan W, Lopez MJ, Hicok K. Adult multipotent stromal cell cryopreservation: Pluses and pitfalls. Vet Surg 2018 Jan;47(1):19-29.
- Esteves CL, Sheldrake TA, Mesquita SP, Pesántez JJ, Menghini T, Dawson L, Péault B, Donadeu FX. Isolation and characterization of equine native MSC populations. Stem Cell Res Ther 2017 Apr 18;8(1):80.
- Esteves CL, Sheldrake TA, Dawson L, Menghini T, Rink BE, Amilon K, Khan N, Péault B, Donadeu FX. Equine Mesenchymal Stromal Cells Retain a Pericyte-Like Phenotype. Stem Cells Dev 2017 Jul 1;26(13):964-972.
- Zahedi M, Parham A, Dehghani H, Mehrjerdi HK. Stemness Signature of Equine Marrow-derived Mesenchymal Stem Cells. Int J Stem Cells 2017 May 30;10(1):93-102.
- Sun T, Yu C, Gao Y, Zhao C, Hua J, Cai L, Guan W, Ma Y. Establishment and biological characterization of a dermal mesenchymal stem cells line from bovine. Biosci Rep 2014 Apr 1;34(2).
- Fülber J, Maria DA, da Silva LC, Massoco CO, Agreste F, Baccarin RY. Comparative study of equine mesenchymal stem cells from healthy and injured synovial tissues: an in vitro assessment. Stem Cell Res Ther 2016 Mar 5;7:35.
- Lombana KG, Goodrich LR, Phillips JN, Kisiday JD, Ruple-Czerniak A, McIlwraith CW. An Investigation of Equine Mesenchymal Stem Cell Characteristics from Different Harvest Sites: More Similar Than Not. Front Vet Sci 2015;2:67.
- Kikuchi J, Koyama D, Wada T, Izumi T, Hofgaard PO, Bogen B, Furukawa Y. Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma. J Clin Invest 2015 Oct 26;125(12):4375-90.
- Sasao T, Fukuda Y, Yoshida S, Miyabara S, Kasashima Y, Kuwano A, Arai K. Population doubling level-dependent change of secreted glycosaminoglycan in equine bone marrow-derived mesenchymal stem cells. J Equine Sci 2015;26(3):73-80.
- Nazari F, Parham A, Maleki AF. GAPDH, β-actin and β2-microglobulin, as three common reference genes, are not reliable for gene expression studies in equine adipose- and marrow-derived mesenchymal stem cells. J Anim Sci Technol 2015;57:18.
- 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.
- Radtke CL, Nino-Fong R, Rodriguez-Lecompte JC, Esparza Gonzalez BP, Stryhn H, McD○ LA. Osteogenic potential of sorted equine mesenchymal stem cell subpopulations. Can J Vet Res 2015 Apr;79(2):101-8.
- 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.
- Alipour F, Parham A, Kazemi Mehrjerdi H, Dehghani H. Equine adipose-derived mesenchymal stem cells: phenotype and growth characteristics, gene expression profile and differentiation potentials. Cell J 2015 Winter;16(4):456-65.
- Fukuta M, Nakai Y, Kirino K, Nakagawa M, Sekiguchi K, Nagata S, Matsumoto Y, Yamamoto T, Umeda K, Heike T, Okumura N, Koizumi N, Sato T, Nakahata T, Saito M, Otsuka T, Kinoshita S, Ueno M, Ikeya M, Toguchida J. Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media. PLoS One 2014;9(12):e112291.
- Radtke CL, Nino-Fong R, Esparza Gonzalez BP, McD○ LA. Application of a novel sorting system for equine mesenchymal stem cells (MSCs). Can J Vet Res 2014 Oct;78(4):290-6.
- Mazor M, Lespessailles E, Coursier R, Daniellou R, Best TM, Toumi H. Mesenchymal stem-cell potential in cartilage repair: an update. J Cell Mol Med 2014 Dec;18(12):2340-50.
- Miyabara S, Yuda Y, Kasashima Y, Kuwano A, Arai K. Regulation of Tenomodulin Expression Via Wnt/β-catenin Signaling in Equine Bone Marrow-derived Mesenchymal Stem Cells. J Equine Sci 2014;25(1):7-13.
- Barberini DJ, Freitas NP, Magnoni MS, Maia L, Listoni AJ, Heckler MC, Sudano MJ, Golim MA, da Cruz Landim-Alvarenga F, Amorim RM. Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord: immunophenotypic characterization and differentiation potential. Stem Cell Res Ther 2014 Feb 21;5(1):25.
- Schnabel LV, Pezzanite LM, Antczak DF, Felippe MJ, Fortier LA. 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 2014 Jan 24;5(1):13.
- Gittel C, Brehm W, Burk J, Juelke H, Staszyk C, Ribitsch I. Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties. BMC Vet Res 2013 Oct 29;9:221.
- Seo MS, Park SB, Kim HS, Kang JG, Chae JS, Kang KS. Isolation and characterization of equine amniotic membrane-derived mesenchymal stem cells. J Vet Sci 2013;14(2):151-9.
- Spaas JH, Guest DJ, Van de Walle GR. Tendon regeneration in human and equine athletes: Ubi Sumus-Quo Vadimus (where are we and where are we going to)?. Sports Med 2012 Oct 1;42(10):871-90.
- Boxall SA, Jones E. Markers for characterization of bone marrow multipotential stromal cells. Stem Cells Int 2012;2012:975871.
- Amos PJ, Cagavi Bozkulak E, Qyang Y. Methods of cell purification: a critical juncture for laboratory research and translational science. Cells Tissues Organs 2012;195(1-2):26-40.
- Raabe O, Shell K, Würtz A, Reich CM, Wenisch S, Arnhold S. Further insights into the characterization of equine adipose tissue-derived mesenchymal stem cells. Vet Res Commun 2011 Aug;35(6):355-65.
- Vachkova E, Arnhold S, Petrova V, Heimann M, Koynarski T, Simeonova G, Piperkov P. Transcriptional Factors Related to Cellular Kinetics, Apoptosis, and Tumorigenicity in Equine Adipose-Derived Mesenchymal Stem Cells (ASCs) Are Influenced by the Age of the Donors. Animals (Basel) 2025 Jun 28;15(13).
- Morawska-Kozłowska M, Pitas M, Zhalniarovich Y. Mesenchymal Stem Cells in Veterinary Medicine-Still Untapped Potential. Animals (Basel) 2025 Apr 19;15(8).
- Yan WT, Wang JS, Fan PZ, Roberts S, Wright K, Zhang ZZ. The clinical potential of meniscal progenitor cells. J Cartil Jt Preserv 2024 Dec;4(4):None.
- Duysens J, Graide H, Niesten A, Mouithys-Mickalad A, Ceusters J, Serteyn D. Optimization of the Amplification of Equine Muscle-Derived Mesenchymal Stromal Cells in a Hollow-Fiber Bioreactor. Methods Protoc 2024 Apr 2;7(2).
- Danev N, Li G, Duan JE, Van de Walle GR. Comparative transcriptomic analysis of bovine mesenchymal stromal cells reveals tissue-source and species-specific differences. iScience 2024 Feb 16;27(2):108886.
- Buonocore M, Grimaldi M, Santoro A, Covelli V, Marino C, Napolitano E, Novi S, Tecce MF, Ciaglia E, Montella F, Lopardo V, Perugini V, Santin M, D'Ursi AM. Exploiting the Features of Short Peptides to Recognize Specific Cell Surface Markers. Int J Mol Sci 2023 Oct 26;24(21).
- Steenbrugge J, Pauwelyn G, Demeyere K, Devriendt N, de Rooster H, Sanders NN, Spaas JH, Meyer E. Xenogeneic equine stem cells activate anti-tumor adaptive immunity in a 4T1-based intraductal mouse model for triple-negative breast cancer: proof-of-principle. Front Immunol 2023;14:1252374.
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