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http://purl.uniprot.org/citations/34863626http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34863626http://www.w3.org/2000/01/rdf-schema#comment"

Background aims

Given their low immunogenicity, immunoregulatory effects and multiple differentiation capacity, mesenchymal stromal cells (MSCs) have the potential to be used for "off-the-shelf" cell therapy to treat various diseases. However, the allorejection of MSCs indicates that they are not fully immune-privileged. In this study, the authors investigated the immunogenicity of human adipose-derived MSCs (Ad-MSCs) and identified potential immunogenic molecules.

Methods

To evaluate the immunogenicity of human Ad-MSCs in vivo, cells were transplanted into humanized mice (hu-mice), then T-cell infiltration and clearance of human Ad-MSCs were observed by immunofluorescence and bioluminescence imaging. One-way mixed lymphocyte reaction and flow cytometry were performed to evaluate the immunogenicity of human Ad-MSCs in vitro. High-throughput T-cell receptor (TCR) repertoire sequencing and mass spectrometry were applied to identified potential immunogenic molecules.

Results

The authors observed that allogeneic Ad-MSCs recruited human T cells and caused faster clearance in hu-mice than non-humanized NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG) mice. The proliferation and activation of T cells were significantly enhanced during in vitro co-culture with human Ad-MSCs. In addition, the level of HLA-II expression on human Ad-MSCs was dramatically increased after co-culture with human peripheral blood mononuclear cells (PBMCs). High-throughput sequencing was applied to analyze the TCR repertoire of the Ad-MSC-recruited T cells to identify dominant TCR CDR3 sequences. Using synthesized TCR CDR3 peptides, the authors identified several potential immunogenic candidates, including alpha-enolase (ENO1). The ENO1 expression level of Ad-MSCs significantly increased after co-culture with PBMCs, whereas ENO1 inhibitor (ENOblock) treatment decreased the expression level of ENO1 and Ad-MSC-induced proliferation of T cells.

Conclusions

The authors' findings improve the understanding of the immunogenicity of human Ad-MSCs and provide a theoretical basis for the safe clinical application of allogeneic MSC therapy."xsd:string
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http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Cao H."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Chen H."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Fu Y."xsd:string
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http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Hu Y."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Li C."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Wang D."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Xu Y."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"He W."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/author"Zhao R.C."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/name"Cytotherapy"xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/pages"393-404"xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/title"Identification of alpha-enolase as a potential immunogenic molecule during allogeneic transplantation of human adipose-derived mesenchymal stromal cells."xsd:string
http://purl.uniprot.org/citations/34863626http://purl.uniprot.org/core/volume"24"xsd:string
http://purl.uniprot.org/citations/34863626http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34863626
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