Cross‐matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting

Autor: Alix K. Berglund, Lauren V. Schnabel, Gwendolyn J. Levine, Douglas F. Antczak, Ashlee E. Watts, Aileen L. Rowland, Donald Miller
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Chemokine
medicine.medical_treatment
Adaptive Immunity
autologous
Major Histocompatibility Complex
humoral
0302 clinical medicine
antibody
Synovial Fluid
allogeneic
lcsh:R5-920
biology
lcsh:Cytology
Histocompatibility Testing
cross‐match
General Medicine
Allografts
Cytokine
Antibody
lcsh:Medicine (General)
major histocompatibility complex (MHC)
Stromal cell
Major histocompatibility complex
Mesenchymal Stem Cell Transplantation
Transplantation
Autologous
MSC
03 medical and health sciences
Immune system
medicine
innate
Synovial fluid
Animals
Horses
lcsh:QH573-671
intra‐articular
business.industry
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Chemokine CXCL12
Immunity
Innate
030104 developmental biology
Immunology
biology.protein
alloimmunization
Enabling Technologies for Cell‐based Clinical Translation
business
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cells Translational Medicine, Vol 10, Iss 5, Pp 694-710 (2021)
Stem Cells Translational Medicine
ISSN: 2157-6564
2157-6580
Popis: 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.
Autologous and matched mesenchymal stromal cell (MSC) intra‐articular transplantation resulted in increased stromal derived factor‐1 and endogenous progenitors, whereas mismatched MSCs resulted in local inflammation, not different to lipopolysaccharide (LPS) injection, and antibody dependent cytotoxicity of MSCs.
Databáze: OpenAIRE
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