Equine Cord Blood Mesenchymal Stromal Cells Have Greater Differentiation and Similar Immunosuppressive Potential to Cord Tissue Mesenchymal Stromal Cells.
Abstract: Mesenchymal stromal cells (MSCs) are the most common cell population studied for therapeutic use in veterinary medicine. MSCs obtained from neonatal sources such as umbilical cord tissue (CT-MSCs) or cord blood (CB-MSCs) are appealing due to the non-invasive nature of procurement and the time allowed for characterization of cells before use. However, it remains unclear as to whether CB- or CT-MSCs have equivalent progenitor and non-progenitor functions. CB-MSCs have been shown to have superior chondrogenic potential to MSCs from other sources, whereas their immunomodulatory capacity does not seem to vary significantly. Using equine CB-MSCs and CT-MSCs from the same donors, we hypothesized that MSCs from both sources would have a similar immunophenotype, that CB-MSCs would be more amenable to differentiation, and that they can equally suppress lymphocyte proliferation. We evaluated cells from both sources for "classic" equine MSC markers CD90, CD105, CD29, and CD44, as well as pericyte markers CD146, NG2, and α-SMA. Contrary to our hypothesis, CB-MSCs showed mid- to high expression of pericyte surface markers CD146 and NG2, whereas expression in CT-MSCs was absent. On trilineage differentiation, CB-MSCs were more osteogenic and chondrogenic based on alkaline phosphatase activity and glycosaminoglycan content, respectively. Finally, using a mononuclear cell (MNC) suppression assay, we determined that both CB-MSCs and CT-MSCs are capable of suppressing stimulated MNC proliferation to a similar degree. We have determined that the choice of MSC tissue source should be made with the intended application in mind. This appears to be particularly relevant if pursuing a progenitor-based treatment strategy.
Publication Date: 2019-01-14
PubMed ID: 30484372DOI: 10.1089/scd.2018.0135Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores the therapeutic potentials of equine (horse) Mesenchymal stromal cells (MSCs) derived from umbilical cord tissue and cord blood, with findings suggesting cord blood MSCs have greater differentiation capacity while both types have similar immunosuppressive potentials.
Study Overview
- The study hinges on the clinical potential of stem cells, specifically MSCs, in veterinary medicine. It discusses the benefits of MSCs derived from neonatal sources like umbilical cord tissue (CT-MSCs) and cord blood (CB-MSCs). These sources are non-invasive and provide an opportunity to study the cells before application.
- The purpose of the study is to compare the progenitor and non-progenitor functions of CB-MSCs and CT-MSCs, focusing on differentiation potential and immunomodulatory capacity specifically.
- Based on previous observations, the researchers hypothesized that though both MSC types would have similar immune-related properties, CB-MSCs would be better suited to differentiation, a key factor in targeted cell therapy.
Analysis and Findings
- The study examined equine CB-MSCs and CT-MSCs using various cell markers (CD90, CD105, CD29, CD44, CD146, NG2, and α-SMA). They found that CB-MSCs had medium to high levels of expression of pericyte surface markers CD146 and NG2, unlike CT-MSCs where these markers were absent.
- In terms of differentiation potential, the researchers found that CB-MSCs were more osteogenic (develop bone) and chondrogenic (develop cartilage), based on the increased levels of alkaline phosphatase activity and glycosaminoglycan content respectively.
- On an immunosuppressive front, both CB-MSCs and CT-MSCs were found to suppress stimulated lymphocyte proliferation to the same degree, confirming their shared immunomodulatory potential.
Conclusions
- The research concludes that the tissue source for MSCs should be chosen carefully, considering the intended application. If a treatment plan is reliant on a progenitor-based strategy, CB-MSCs could be a more effective choice due to their superior differentiation potential.
- However, if the treatment approach requires immunomodulatory properties, both CB-MSCs and CT-MSCs would be similarly suitable. This comparability between the two MSC types underscores the importance of selecting the correct tissue source based on the therapeutic goals.
Cite This Article
APA
Lepage SIM, Lee OJ, Koch TG.
(2019).
Equine Cord Blood Mesenchymal Stromal Cells Have Greater Differentiation and Similar Immunosuppressive Potential to Cord Tissue Mesenchymal Stromal Cells.
Stem Cells Dev, 28(3), 227-237.
https://doi.org/10.1089/scd.2018.0135
Publication
Researcher Affiliations
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Canada.
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Canada.
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Canada.
MeSH Terms
- Animals
- Cell Differentiation
- Cell Proliferation
- Cells, Cultured
- Chondrocytes / cytology
- Chondrocytes / metabolism
- Female
- Fetal Blood / cytology
- Horses
- Lymphocytes / immunology
- Lymphocytes / physiology
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / immunology
- Pericytes / cytology
- Pericytes / metabolism
- Pregnancy
- Umbilical Cord / cytology
Citations
This article has been cited 7 times.- Lu00f3pez-Jimu00e9nez C, Chiu LLY, Waldman SD, Guilak F, Koch TG. TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets.. Osteoarthr Cartil Open 2022 Jun;4(2):100263.
- 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.
- 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).
- Lee OJ, Koch TG. Steps Toward Standardized In Vitro Assessment of Immunomodulatory Equine Mesenchymal Stromal Cells Before Clinical Application.. Stem Cells Dev 2022 Jan;31(1-2):18-25.
- Wright A, Arthaud-Day ML, Weiss ML. Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species.. Front Cell Dev Biol 2021;9:632717.
- 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.
- Boruczkowski D, Pujal JM, Zdoliu0144ska-Malinowska I. Autologous cord blood in children with cerebral palsy: a review.. Int J Mol Sci 2019 May 16;20(10).