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Home / Equine Research Bank / Animals (Basel) / Equine Mesenchymal Stem Cells Influence the Proliferative Re...
Animals : an open access journal from MDPI2022; 12(8); 984; doi: 10.3390/ani12080984

Equine Mesenchymal Stem Cells Influence the Proliferative Response of Lymphocytes: Effect of Inflammation, Differentiation and MHC-Compatibility.

Abstract: Immunomodulation and immunogenicity are pivotal aspects for the therapeutic use of mesenchymal stem cells (MSCs). Since the horse is highly valuable as both a patient and translational model, further knowledge on equine MSC immune properties is required. This study analysed how inflammation, chondrogenic differentiation and compatibility for the major histocompatibility complex (MHC) influence the MSC immunomodulatory-immunogenicity balance. Equine MSCs in basal conditions, pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were co-cultured with either autologous or allogeneic MHC-matched/mismatched lymphocytes in immune-suppressive assays (immunomodulation) and in modified one-way mixed leukocyte reactions (immunogenicity). After co-culture, frequency and proliferation of T cell subsets and B cells were assessed by flow cytometry and interferon-ɣ (IFNɣ) secretion by ELISA. MSC-primed showed higher regulatory potential by decreasing proliferation of cytotoxic and helper T cells and B cells. However, MHC-mismatched MSC-primed can also activate lymphocytes (proliferative response and IFNɣ secretion), likely due to increased MHC-expression. MSC-chondro maintained their regulatory ability and did not increase their immunogenicity, but showed less capacity than MSC-primed to induce regulatory T cells and further stimulated B cells. Subsequent in vivo studies are needed to elucidate the complex interactions between MSCs and the recipient immune system, which is critical to develop safe and effective therapies.
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Publication Date: 2022-04-11 PubMed ID: 35454231PubMed Central: PMC9031781DOI: 10.3390/ani12080984Google Scholar: Lookup
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  • Journal Article

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 study investigated how inflammation, differentiation towards cartilage cells, and compatibility of cells of the immune system impact the influence of horse mesenchymal stem cells (MSCs) on the immune response.

Research Context and Purpose

  • The study aims to expand the understanding of how horse mesenchymal stem cells (MSCs) can modulate the immune system. This is critical for therapeutic applications of MSCs in horses, which are also a valuable model organism for human disease.
  • Specifically, the researchers examined how inflammation, differentiation into cartilage cells, and major histocompatibility complex (MHC) compatibility—how well the MSCs match with immune system cells—can affect the balance between the MSCs’ immunomodulatory (ability to alter immune responses) and immunogenic (ability to evoke an immune response) characteristics.

Research Methodology

  • The researchers cultured MSCs in normal conditions, in conditions that mimic inflammation (termed MSC-primed), or differentiated them into cartilage cells (termed MSC-chondro).
  • These MSCs were then cultured together with lymphocytes (T cells and B cells), two key immune cells of the body, either from the same horse (autologous) or from different, MHC-matched or mismatched horses (allogeneic).
  • The researchers then examined how the different MSC-lymphocyte co-cultures affected the proliferation and activation of T cells and B cells via flow cytometry and interferon-γ (IFNɣ) secretion measurement. IFNɣ is a molecule associated with immune cell activation.

Key Findings

  • In MSC-primed conditions, there was an increased ability to decrease the proliferation of cytotoxic T cells, helper T cells, and B cells. This indicates that these cells have a high regulatory capacity, helping to control the activity of the immune system.
  • However, when MHC-mismatched MSC-primed cells were cultured, it was found that they could still activate lymphocytes. This could be due to increased MHC expression, showing the potential immunogenicity of the MSCs.
  • Likewise, MSCs differentiated into cartilage cells (MSC-chondro) were able to maintain their ability to regulate the immune system but had decreased capacity in comparison to MSC-primed cells. They showed a lower tendency to stimulate regulatory T cells, while proliferating B cells further.
  • In summary, the results provide valuable insights into the immunomodulatory and immunogenic properties of MSCs, based on their state of differentiation and immune system compatibility.

Implications

  • The findings advance our understanding of how horse MSCs interact with the immune system, given different conditions. This knowledge is critical for developing safe and effective therapies using MSCs, as the balance between immunomodulatory and immunogenic properties could impact therapeutic outcomes.
  • The study’s outcomes also underline the importance of further in vivo (in the body) studies to delineate the complex interactions between MSCs and the recipient immune system.

Cite This Article

APA
Cequier A, Romero A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Zaragoza P, Rodellar C, Barrachina L. (2022). Equine Mesenchymal Stem Cells Influence the Proliferative Response of Lymphocytes: Effect of Inflammation, Differentiation and MHC-Compatibility. Animals (Basel), 12(8), 984. https://doi.org/10.3390/ani12080984

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 12
Issue: 8
PII: 984

Researcher Affiliations

Cequier, Alina
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
  • Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza, 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.
Romero, Antonio
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, 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.
Vázquez, Francisco J
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, 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.
Vitoria, Arantza
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, 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.
Bernad, Elvira
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
Fuente, Sara
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, 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, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
  • Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
Rodellar, Clementina
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
  • Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
Barrachina, Laura
  • Laboratorio de Genética Bioquímica LAGENBIO, Instituto de Investigación Sanitaria de Aragón (IIS), Universidad de Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain.
  • Instituto Agroalimentario de Aragón-IA2, Universidad de Zaragoza, 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.

Grant Funding

  • AGL2017-84411-P / Ministerio de Industria, Economu00eda y Competitividad, Espau00f1a

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Citations

This article has been cited 2 times.
  1. Barrachina L, Arshaghi TE, O'Brien A, Ivanovska A, Barry F. Induced pluripotent stem cells in companion animals: how can we move the field forward?. Front Vet Sci 2023;10:1176772.
    doi: 10.3389/fvets.2023.1176772pubmed: 37180067google scholar: lookup
  2. 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.
    doi: 10.3389/fvets.2022.957153pubmed: 36337202google scholar: lookup
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