title: Mesenchymal stem cells inhibit thymic reconstitution after allogeneic cord blood transplantation.
abstract: Cord blood (CB) as a source of stem cells has been a successful addition to the field of allogeneic stem cell transplantation (ASCT). The increased human leukocyte antigen (HLA) permissiveness of CB grafts has made it possible for more patients to undergo treatment. The drawback is that patients suffer from a longer period of compromised immunity. We analyzed T-cell receptor excision circles (TRECs), immunoglobulin G (IgG), and immunoglobulin M (IgM) levels after cord blood transplantation (CBT) in 50 patients transplanted at our center. These immunological parameters were compared retrospectively with clinical factors and complications. We found that TREC levels after CBT were lower in adults, patients with myeloablative conditioning, and in patients with a lower nucleated cell dose in the graft. In addition mesenchymal stem cells (MSC) as co-infusion at the time of CBT had a negative effect on TREC reconstitution. This was found to be associated with decreased overall survival for this patient category. Reduced IgM and IgG levels post-CBT were associated with a major AB0 mismatch, and infusion of MSCs. Our results highlight the importance of close monitoring of the immune reconstitution after CBT. In addition it shows a potentially new suppressive effect of MSCs on the immune system.
authors.affiliation: Clinical Immunology Unit, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. michael.uhlin@ki.se
authors.forename: Michael
authors.initials: M
authors.lastname: Uhlin
authors.forename: Darius
authors.initials: D
authors.lastname: Sairafi
authors.forename: Sofia
authors.initials: S
authors.lastname: Berglund
authors.forename: Sarah
authors.initials: S
authors.lastname: Thunberg
authors.forename: Jens
authors.initials: J
authors.lastname: Gertow
authors.forename: Olle
authors.initials: O
authors.lastname: Ringden
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzunel
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D006680:HLA Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000276:immunology; D012189:Retrospective Studies; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011948:Receptors, Antigen, T-Cell