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Stem cells translational medicine2020; 10(5); 694-710; doi: 10.1002/sctm.20-0435

Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting.

Abstract: Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared with recipients receiving matched allogeneic or autologous MSCs. Importantly, in matched allogeneic and autologous recipients, but not mismatched allogeneic recipients, there was increased stromal derived factor-1 along with increased MSC concentrations in synovial fluid. Until immune recognition of MSCs can be avoided, repeated clinical use of MSCs should be limited to autologous or cross-matched allogeneic MSCs. When non-cross-matched allogeneic MSCs are used in single MSC dose applications, presensitization against donor MHC should be assessed.
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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Publication Date: 2020-12-25 PubMed ID: 33369287PubMed Central: PMC8046071DOI: 10.1002/sctm.20-0435Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

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 study reports that allogeneic mesenchymal stromal cells (MSCs), often used in treatments without cross-matching based on the presumption they are immune-privileged, can actually lead to innate and adaptive immune responses if they don’t match the patient’s major histocompatibility complex (MHC). The researchers, using an equine model, note that these contradictory responses can be avoided by either using autologous MSCs or engaging in cross-matching, therefore, avoiding repeated clinical use of non-cross-matched MSCs.

Understanding Mesenchymal Stromal Cells (MSCs)

  • Mesenchymal stromal cells (MSCs) are multipotent stem cells that have been used in clinical treatments for many years.
  • These cells have been historically considered “immune-privileged,” meaning that they have been thought to not trigger immune responses in patients, thereby allowing them to be utilized without cross-checking their compatibility with the patient’s immune system.

The Experiment and Its Findings

  • Contrary to the prevailing belief, researchers found that repeated injection of major histocompatibility complex (MHC) mismatched allogeneic MSCs in horses led to innate and adaptive immune responses.
  • This outcome showed itself in the form of increased peri-articular edema and synovial effusion, higher levels of synovial cytokine and chemokine, and the development of donor-specific antibodies in recipients.
  • These adverse effects, however, were not observed when MHC matched allogeneic or autologous MSCs were used, as there was the presence of stromal derived factor-1 along with increased MSC concentrations in synovial fluid. This means successful MSC treatment relies on the compatibility of MHCs or the use of one’s own MSCs, autologous MSCs.

Implications for Clinical Practice

  • The findings of this study suggest that the existing clinical practice of using allogeneic MSCs without cross-matching should be adjusted.
  • When non-cross-matched allogeneic MSCs are used in single MSC dose applications, presensitization against donor MHC should be assessed to minimize immune-related complications.
  • Most importantly, repeated clinical use of MSCs should be limited to autologous or cross-matched allogeneic MSCs, to mitigate immune responses.

Cite This Article

APA
Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE. (2020). Cross-matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting. Stem Cells Transl Med, 10(5), 694-710. https://doi.org/10.1002/sctm.20-0435

Publication

Stem cells translational medicine
ISSN: 2157-6580
NlmUniqueID: 101578022
Country: England
Language: English
Volume: 10
Issue: 5
Pages: 694-710

Researcher Affiliations

Rowland, Aileen L
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA.
Miller, Donald
  • Baker Institute for Animal Health, Cornell University, Ithaca, New York, USA.
Berglund, Alix
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Schnabel, Lauren V
  • Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Levine, Gwendolyn J
  • Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, USA.
Antczak, Douglas F
  • Baker Institute for Animal Health, Cornell University, Ithaca, New York, USA.
Watts, Ashlee E
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, Texas, USA.

MeSH Terms

  • Adaptive Immunity
  • Allografts
  • Animals
  • Chemokine CXCL12
  • Histocompatibility Testing / veterinary
  • Horses
  • Immunity, Innate
  • Major Histocompatibility Complex
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells
  • Synovial Fluid / immunology
  • Transplantation, Autologous

Conflict of Interest Statement

L.V.S. declared honoraria from Arthrex Inc and cofounder of Vetletics Inc. The other authors declared no potential conflicts of interest.

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Citations

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