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Veterinary immunology and immunopathology2018; 200; 1-6; doi: 10.1016/j.vetimm.2018.04.004

Differentiation of equine bone marrow derived mesenchymal stem cells increases the expression of immunogenic genes.

Abstract: Mesenchymal stem cells (MSCs) are a promising treatment for equine musculoskeletal injuries because of their ability to regulate the inflammation and to differentiate into other cell types. Since interest in allogeneic therapy is rising, concerns about MSC immunogenicity need to be addressed. Differentiated MSCs from several species increase their expression of immunogenic molecules and induce alloresponses, but equine MSC immunogenic profile after differentiation has not been reported. Therefore, the aim of this study was to assess the gene expression of immunogenic markers in tri-lineage differentiated equine bone marrow derived MSCs (eBM-MSCs). For this purpose, eBM-MSCs (n = 4) were differentiated into osteoblasts, adipocytes and chondrocytes. Differentiation was confirmed by specific staining and gene expression of lineage-related markers. Subsequently, gene expression of MHC-I, MHC-II, CD40 and CD80 was analyzed in undifferentiated (control) and tri-lineage differentiated eBM-MSCs. Osteogenesis and adipogenesis, but not chondrogenesis, significantly upregulated MHC-I; MHC-II expression significantly increased in the three lineages, while CD40 and CD80 expression did not change. Despite this, MHC-I and MHC-II upregulation after differentiation might lead to increased immunogenicity and risk of allorecognition, either eBM-MSCs differentiate in vivo after administration or they are differentiated prior to administration, with potential negative consequences for effectiveness and safety of allogeneic therapy.
Publication Date: 2018-04-14 PubMed ID: 29776607DOI: 10.1016/j.vetimm.2018.04.004Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates how the process of differentiation, where mesenchymal stem cells (MSCs) transform into distinct cell types, affects their immunogenicity – their ability to provoke an immune response – in horses. The conclusion is that differentiation increases the expression of certain immunogenic genes, with potential implications for the efficacy and safety of treatments involving these cells.

Objectives of the Study

  • The primary purpose of the study was to evaluate the gene expression of immunogenic markers – specifically MHC-I, MHC-II, CD40 and CD80 – in mesenchymal stem cells (MSCs) from equine bone marrow, before and after they had differentiated into other cell types.
  • This research was conducted in light of growing interest in allogenic therapies, treatments using donated stem cells, which require full understanding of any potential immune response that may be triggered.
  • Investigations into such reactions has been done for other species, but not yet studied in equine MSCs.

Methodology of the Research

  • In the study, MSCs were extracted from equine bone marrow (4 individual samples).
  • The cells were then induced to differentiate into three types of cells: osteoblasts (bone-forming cells), adipocytes (fat cells), and chondrocytes (cartilage cells).
  • The researchers then confirmed this differentiation using specific dye staining and by analyzing the expression of genes associated with each cell type.
  • During this process, the expression of immunogenic markers – MHC-I, MHC-II, CD40 and CD80 – was continually analyzed.

Findings from the Research

  • Significant increases in the gene expression of MHC-I and MHC-II were noted during the differentiation into osteoblasts and adipocytes, but not into chondrocytes.
  • The expressions of CD40 and CD80 did not change significantly.
  • These findings indicate that the differentiation process, either before or after administration of MSCs within the body, could increase their immunogenicity. This carries potential risks of allorecognition, where the immune system identifies the MSCs as foreign and possibly harmful.

Implications from the Research

  • The findings suggest that differentiation of equine MSCs increases their immunogenicity, and this could hamper the effectiveness and safety of allogenic treatments using these cells.
  • This calls for further research into how the immunogenic characteristics of MSCs could be managed or mitigated in treatment contexts.
  • Additionally, the immunogenic differences between differentiated and undifferentiated MSCs, as well as between different cell types, could be studied further.

Cite This Article

APA
Barrachina L, Remacha AR, Romero A, Zaragoza P, Vázquez FJ, Rodellar C. (2018). Differentiation of equine bone marrow derived mesenchymal stem cells increases the expression of immunogenic genes. Vet Immunol Immunopathol, 200, 1-6. https://doi.org/10.1016/j.vetimm.2018.04.004

Publication

ISSN: 1873-2534
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 200
Pages: 1-6
PII: S0165-2427(17)30451-8

Researcher Affiliations

Barrachina, Laura
  • Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177. 50013 Zaragoza, Spain.
Remacha, Ana Rosa
  • Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain.
Romero, Antonio
  • Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177. 50013 Zaragoza, Spain.
Zaragoza, Pilar
  • Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain.
Vázquez, Francisco José
  • Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain; Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, C/Miguel Servet, 177. 50013 Zaragoza, Spain.
Rodellar, Clementina
  • Laboratorio de Genética Bioquímica LAGENBIO (Universidad de Zaragoza), Instituto Agroalimentario de Aragón- IA2, (Universidad de Zaragoza-CITA), Instituto de Investigación Sanitaria de Aragón (IIS), C/Miguel Servet, 177, 50013 Zaragoza, Spain. Electronic address: rodellar@unizar.es.

MeSH Terms

  • Adipogenesis
  • Animals
  • B7-1 Antigen / metabolism
  • Bone Marrow Cells / metabolism
  • CD40 Antigens / metabolism
  • Cell Differentiation / genetics
  • Chondrogenesis
  • Gene Expression / genetics
  • Genes, MHC Class I
  • Genes, MHC Class II
  • Horses
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis
  • Real-Time Polymerase Chain Reaction / veterinary

Citations

This article has been cited 5 times.
  1. 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).
    doi: 10.3390/ani12080984pubmed: 35454231google scholar: lookup
  2. 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.
    doi: 10.3389/fvets.2020.617647pubmed: 33521090google scholar: lookup
  3. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
    doi: 10.3390/ani11010234pubmed: 33477808google scholar: lookup
  4. MacDonald ES, Barrett JG. The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.. Front Vet Sci 2019;6:507.
    doi: 10.3389/fvets.2019.00507pubmed: 32039250google scholar: lookup
  5. Rodas G, Soler R, Balius R, Alomar X, Peirau X, Alberca M, Sánchez A, Sancho JG, Rodellar C, Romero A, Masci L, Orozco L, Maffulli N. Autologous bone marrow expanded mesenchymal stem cells in patellar tendinopathy: protocol for a phase I/II, single-centre, randomized with active control PRP, double-blinded clinical trial.. J Orthop Surg Res 2019 Dec 16;14(1):441.
    doi: 10.1186/s13018-019-1477-2pubmed: 31842921google scholar: lookup