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Stem cell research & therapy2020; 11(1); 99; doi: 10.1186/s13287-020-01611-z

Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells.

Abstract: Equine amniotic mesenchymal stromal cells (AMSCs) and their conditioned medium (CM) were evaluated for their ability to inhibit in vitro proliferation of peripheral blood mononuclear cells (PBMCs) with and without priming. Additionally, AMSC immunogenicity was assessed by expression of MHCI and MHCII and their ability to counteract the in vitro inflammatory process. Horse PBMC proliferation was induced with phytohemagglutinin. AMSC priming was performed with 10 ng/ml of TNF-α, 100 ng/ml of IFN-γ, and a combination of 5 ng/ml of TNF-α and 50 ng/ml of IFN-γ. The CM generated from naïve unprimed and primed AMSCs was also tested to evaluate its effects on equine endometrial cells in an in vitro inflammatory model induced by LPS. Immunogenicity marker expression (MHCI and II) was evaluated by qRT-PCR and by flow cytometry. Priming does not increase MHCI and II expression. Furthermore, the inhibition of PBMC proliferation was comparable between naïve and conditioned cells, with the exception of AMSCs primed with both TNF-α and IFN-γ that had a reduced capacity to inhibit T cell proliferation. However, AMSC viability was lower after priming than under other experimental conditions. CM from naïve and primed AMSCs strongly inhibited PBMC proliferation and counteracted the inflammatory process, rescuing about 65% of endometrial cells treated by LPS. AMSCs and their CM have a strong capacity to inhibit PBMC proliferation, and priming is not necessary to improve their immunosuppressive activity or reactivity in an inflammatory in vitro model.
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Publication Date: 2020-03-04 PubMed ID: 32131892PubMed Central: PMC7055152DOI: 10.1186/s13287-020-01611-zGoogle Scholar: Lookup
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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 immune-suppressive capabilities and responsiveness of horse amniotic mesenchymal stromal cells (AMSCs). The findings suggest that “priming” or pre-stimulating these cells doesn’t necessarily enhance their ability to inhibit the inflammation process or immune cell proliferation.

Research Objectives and Methods

The study set out to assess the immune-suppressive properties and responsiveness of AMSCs and their conditioned medium (CM – the environment where cells have grown and that they have subsequently altered). The researchers wanted to compare these characteristics under both primed (pre-stimulated with inflammatory substances) and unprimed situations. Evaluations were made based on:

  • The cells’ capacity to impede the in vitro (in a controlled lab environment) proliferation of peripheral blood mononuclear cells (PBMCs), which are important components of the body’s immune system.
  • The cells’ immunogenicity, or their ability to provoke an immune response, assessed by expressing MHCI and MHCII—markers that play a critical role in the immune system’s recognition of foreign substances.
  • The ability to counteract the in vitro inflammatory process.

Key Findings

The research yielded several significant findings:

  • AMSCs displayed the power to hinder the proliferation of PBMCs, and their immunosuppressive activity was similar with or without being primed.
  • The study observed no increase in the expression of the MHCI and MHCII markers following priming, implying that priming does not enhance the cells’ immunogenicity.
  • AMSCs primed with both TNF-α and IFN-γ (inflammatory substances) had slightly lower capacity to inhibit T cell (type of PBMC) proliferation, and these cells also exhibited lesser viability after priming.
  • In a LPS-induced in vitro inflammatory model, CM from both unprimed and primed AMSCs noticeably inhibited PBMC proliferation and countered the inflammatory process, saving around 65% of treated endometrial cells.

Conclusion

The researchers concluded that amniotic mesenchymal stromal cells and their conditioned medium possess significant potency to inhibit PBMC proliferation. Therefore, priming the cells is not vital to enhance their immunosuppressive function or responsiveness in an in vitro inflammatory situation. Thus, this research provides valuable insight into the therapeutic potential of equine AMSCs for treating inflammatory diseases.

Cite This Article

APA
Lange-Consiglio A, Romele P, Magatti M, Silini A, Idda A, Martino NA, Cremonesi F, Parolini O. (2020). Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells. Stem Cell Res Ther, 11(1), 99. https://doi.org/10.1186/s13287-020-01611-z

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 99
PII: 99

Researcher Affiliations

Lange-Consiglio, Anna
  • Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Via dell'Università 6, 26900, Lodi, Italy. anna.langeconsiglio@unimi.it.
Romele, Pietro
  • Centro Ricerca E. Menni, Fondazione Poliambulanza di Brescia, Via Bissolati 57, 25124, Brescia, Italy.
Magatti, Marta
  • Centro Ricerca E. Menni, Fondazione Poliambulanza di Brescia, Via Bissolati 57, 25124, Brescia, Italy.
Silini, Antonietta
  • Centro Ricerca E. Menni, Fondazione Poliambulanza di Brescia, Via Bissolati 57, 25124, Brescia, Italy.
Idda, Antonella
  • Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Via dell'Università 6, 26900, Lodi, Italy.
Martino, Nicola Antonio
  • Department of Veterinary Science, University of Torino, Via Leonardo da Vinci 44, 10095, Turin, Italy.
Cremonesi, Fausto
  • Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Via dell'Università 6, 26900, Lodi, Italy.
Parolini, Ornella
  • Centro Ricerca E. Menni, Fondazione Poliambulanza di Brescia, Via Bissolati 57, 25124, Brescia, Italy.
  • Department of Life Scince and Public Health, Università Cattolica del Sacro Cuore di Roma, Largo F. Vito 1, 00168, Rome, Italy.

MeSH Terms

  • Amnion
  • Animals
  • Cells, Cultured
  • Culture Media, Conditioned
  • Cytokines / genetics
  • Horses
  • Leukocytes, Mononuclear
  • Mesenchymal Stem Cells

Conflict of Interest Statement

The authors declare that they have no competing interests.

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