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Journal of clinical medicine2018; 7(11); 383; doi: 10.3390/jcm7110383

Immunomodulatory Properties of Adipose-Derived Stem Cells Treated with 5-Azacytydine and Resveratrol on Peripheral Blood Mononuclear Cells and Macrophages in Metabolic Syndrome Animals.

Abstract: Endocrine disorders, including equine metabolic syndrome (EMS), are a serious issue in veterinary medicine and horse breeding. Furthermore, EMS was shown to affect the cytophysiological properties of adipose-derived stem cells, reducing their therapeutic potential. However, it was shown that those cells can be rejuvenated while using a combination of two chemicals: 5-azacytydine (AZA) and resveratrol (RES). In the present study, we decided to evaluate the immunomodulatory properties of AZA/RES-treated adipose-derived stem cells (ASC) isolated from EMS horses (ASC). Thus, we co-cultured ASC with peripheral blood mononuclear cells (PBMC) and RAW264.7 macrophages. Most attention was placed on regulatory T lymphocytes (T), as well as the messenger RNA (mRNA) and protein levels of several cytokines (tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-10, and IL-1β). Moreover, we also investigated the expression of genes related to auto- and mitophagy in both PBMCs and ASCs. PBMCs were obtained from healthy and EMS-suffering individuals and were co-cultured with ASCs that were isolated from healthy and EMS horses cultured in control conditions and with AZA/RES. We discovered that cells treated with AZA/RES increase the T number while co-cultured with PBMCs. Moreover, the co-culture of PBMCs with AZA/RES-treated ASC induced mitophagy in PBMCs. Furthermore, ASC pre-treated with AZA/RES displayed anti-inflammatory properties, as decreased levels of TNF-α, nitric oxide (NO), and IL-6 were observed in those cells in comparison with their untreated counterparts in the co-culture with RAW264.7 macrophages. In summary, we demonstrated that ASC treated with AZA/RES displayed increased anti-inflammatory properties, and was able to regulate and activate the T-related anti-inflammatory response.
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Publication Date: 2018-10-24 PubMed ID: 30356025PubMed Central: PMC6262510DOI: 10.3390/jcm7110383Google 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 article centers around the study of immunomodulatory properties of rejuvenated stem cells extracted from horses with equine metabolic syndrome (EMS) when treated with a combination of two chemicals: 5-azacytydine (AZA) and resveratrol (RES). The adjective ‘immunomodulatory’ refers to the ability to modify or regulate the functioning of the immune system. The study found that the treated stem cells not only displayed increased anti-inflammatory properties but also successfully activated T-related anti-inflammatory response.

Research Methodology

  • The study conducted experiments using adipose-derived stem cells (ASC), isolated from EMS affected horses, which were treated with a chemical combination of 5-azacytydine (AZA) and resveratrol (RES).
  • These treated cells were co-cultured with peripheral blood mononuclear cells (PBMC) and RAW264.7 macrophages.
  • Focused study was conducted on the regulatory T lymphocytes.
  • The changes in messenger RNA (mRNA) and protein levels of several cytokines, namely, tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-10, and IL-1β, were observed.
  • Futhermore, the research investigated into the expression of genes related to auto- and mitophagy in both PBMCs and ASCs.

Findings and Conclusions

  • The study discovered that the cells treated with AZA/RES increased the number of regulatory T lymphocytes, which are crucial in preventing autoimmune diseases by suppressing overactive immune responses, when co-cultured with PBMCs.
  • Successful induction of mitophagy in PBMCs was observed when they were co-cultured with AZA/RES-treated ASC. Mitophagy is the selective degradation of mitochondria by autophagy, which is often initiated in response to cellular stress.
  • Furthermore, it was noticed that ASC pre-treated with AZA/RES exhibited anti-inflammatory properties, as witnessed by the decrease in the levels of TNF-α, nitric oxide (NO), and IL-6 compared to their untreated counterparts when co-cultured with RAW264.7 macrophages.
  • In conclusion, the study demonstrated that ASC treated with AZA/RES showcased increased anti-inflammatory properties and acquired the capability to regulate and activate T cell-related anti-inflammatory response.

Impact of the Research

  • This research contributes significantly to the realm of veterinary medicine and horse breeding as endocrine disorders, especially EMS, are persistent issues in these fields.
  • The study showcases the potential of the chemical treatment of ASC, using AZA and RES, in rejuvenating the immunomodulatory properties of cells, which can open avenues to new approaches in treating EMS and potentially other endocrine disorders in horses.
  • The finding that the treated ASCs can effectively stimulate the T cell-related anti-inflammatory response also adds a new dimension to the ongoing research in immune system regulation and autoimmunity.

Cite This Article

APA
Kornicka K, Śmieszek A, Węgrzyn AS, Röcken M, Marycz K. (2018). Immunomodulatory Properties of Adipose-Derived Stem Cells Treated with 5-Azacytydine and Resveratrol on Peripheral Blood Mononuclear Cells and Macrophages in Metabolic Syndrome Animals. J Clin Med, 7(11), 383. https://doi.org/10.3390/jcm7110383

Publication

Journal of clinical medicine
ISSN: 2077-0383
NlmUniqueID: 101606588
Country: Switzerland
Language: English
Volume: 7
Issue: 11
PII: 383

Researcher Affiliations

Kornicka, Katarzyna
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences Wroclaw 50-375, Poland. kornicka.katarzyna@gmail.com.
Śmieszek, Agnieszka
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences Wroclaw 50-375, Poland. smieszek.agnieszka@gmail.com.
Węgrzyn, Agnieszka Sławomira
  • PORT Polish Center for Technology Development, Wrocław 54-066, Poland. agnieszka.wegrzyn@eitplus.pl.
Röcken, Michael
  • Faculty of Veterinary Medicine, Equine Clinic-Equine Surgery, Justus-Liebig-University, Giessen 35392, Germany. Michael.Roecken@vetmed.uni-giessen.de.
Marycz, Krzysztof
  • Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences Wroclaw 50-375, Poland. krzysztofmarycz@interia.pl.
  • Faculty of Veterinary Medicine, Equine Clinic-Equine Surgery, Justus-Liebig-University, Giessen 35392, Germany. krzysztofmarycz@interia.pl.

Grant Funding

  • 2016/21/B/NZ7/01111 / Narodowe Centrum Nauki
  • - / Krajowy Naukowy Osrodek Wiodacy

Conflict of Interest Statement

The authors declare that there is no conflict of interest.

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