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Frontiers in cell and developmental biology2021; 9; 628382; doi: 10.3389/fcell.2021.628382

TGF-β2 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties.

Abstract: Allogeneic mesenchymal stem cells (MSCs) are a promising cell therapy for treating numerous diseases, but major histocompatibility complex (MHC)-mismatched MSCs can be rejected by the recipient's immune system. Pre-treating MSCs with transforming growth factor-β2 (TGF-β2) to downregulate surface expression of MHC molecules may enhance the ability of allogeneic MSCs to evade immune responses. We used lymphocyte proliferation assays and ELISAs to analyze the immunomodulatory potential of TGF-β2-treated equine bone marrow-derived MSCs. T cell activation and cytotoxicity assays were then used to measure the cell-mediated immunogenicity. Similar to untreated MSCs, TGF-β2-treated MSCs inhibited T cell proliferation and did not stimulate MHC-mismatched T cells to proliferate. Additionally, similar quantities of prostaglandin E2 and TGF-β1 were detected in assays with untreated and TGF-β2-treated MSCs supporting that TGF-β2-treated MSCs retain their strong immunomodulatory properties . Compared to untreated MSCs, TGF-β2-treated MSCs induced less T cell activation and had reduced cell-mediated cytotoxicity . These results indicate that treating MSCs with TGF-β2 is a promising strategy to reduce the cell-mediated immunogenicity of MHC-mismatched MSCs and facilitate allogeneic MSC therapy.
Copyright © 2021 Berglund, Long, Robertson and Schnabel.
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Publication Date: 2021-02-04 PubMed ID: 33614658PubMed Central: PMC7889809DOI: 10.3389/fcell.2021.628382Google 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.

This research asserts that treatment of mesenchymal stem cells (MSCs) with TGF-β2 reduces their susceptibility to immune responses without adversely affecting their immunomodulatory functions, making this method a prospective tool for enhancing successful MSC therapy.

Background of the Study

  • The study is based on the lab investigation into the potential of transforming growth factor-β2 (TGF-β2) in the treatment of equine bone marrow-derived mesenchymal stem cells (MSCs). MSCs are therapeutic cells that hold promise in tackling a variety of diseases.
  • The challenges with the clinical use of these cells usually stem from the risks of rejection by the recipient’s immune system due to MHC-mismatching. To address this, the MSCs can be pre-treated, as proposed, with the TGF-β2 to downregulate the surface expression of MHC molecules and thus helping them evade immune responses.

Methodology of the Research

  • Researchers utilized lymphocyte proliferation assays and ELISA tests to assess the immunomodulatory potential of TGF-β2-treated equine bone marrow-derived MSCs.
  • Assessment of the cell-mediated immunogenicity was determined through T cell activation and cytotoxicity assays.

Findings of the Study

  • The findings revealed that, like untreated MSCs, TGF-β2-treated MSCs inhibited the growth of T cells and did not stimulate proliferation in MHC-mismatched T cells.
  • Moreover, assays carried out with untreated and TGF-β2-treated MSCs found comparable quantities of prostaglandin E2 and TGF-β1, indicating that TGF-β2-treated MSCs maintain their strong immunomodulatory properties.
  • When compared with untreated MSCs, TGF-β2-treated MSCs triggered less T cell activation and exhibited reduced cell-mediated cytotoxicity.

Conclusion of the Study

  • The results obtained from the study signify that the application of TGF-β2 in the treatment of MSCs is a constructive strategy that can reduce the cell-mediated immunogenicity of MHC-mismatched MSCs.
  • This strategy could aid in the easy implementation of allogenic MSC therapy by helping the MSCs evade immune response, thereby preventing cell rejection.

Cite This Article

APA
Berglund AK, Long JM, Robertson JB, Schnabel LV. (2021). TGF-β2 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties. Front Cell Dev Biol, 9, 628382. https://doi.org/10.3389/fcell.2021.628382

Publication

Frontiers in cell and developmental biology
ISSN: 2296-634X
NlmUniqueID: 101630250
Country: Switzerland
Language: English
Volume: 9
Pages: 628382
PII: 628382

Researcher Affiliations

Berglund, Alix K
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Long, Julie M
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Robertson, James B
  • Office of Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Schnabel, Lauren V
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.

Grant Funding

  • K01 OD027037 / NIH HHS
  • K08 AR060875 / NIAMS NIH HHS

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Citations

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