
Cross‐matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting
Author(s) -
Rowland Aileen L.,
Miller Donald,
Berglund Alix,
Schnabel Lauren V.,
Levine Gwendolyn J.,
Antczak Douglas F.,
Watts Ashlee E.
Publication year - 2021
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.20-0435
Subject(s) - mesenchymal stem cell , immunology , medicine , immune system , stromal cell , chemokine , major histocompatibility complex , cancer research , pathology
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.