No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients.
OBJECTIVE
Mesenchymal stromal cells (MSC) may be used in cellular therapy to treat graft-versus-host-disease and autoimmune disorders, and in regenerative medicine. Preliminary data suggest limited cellular allogeneic rejection, but less is known about humoral responses. The objective of this study was to investigate whether antibodies against MSC were present after hematopoietic stem cell transplantation (HSCT) including treatment with matched or mismatched allogeneic MSC.


METHODS
Twelve patients were evaluated using flow cytometric cross matches (FCXM) and enzyme-linked immunosorbent assays. Expression of blood group antigens, regarded as alloantigens giving rise to humoral alloimmunity, on MSC were explored using flow cytometry and immunofluorescence.


RESULTS
Three of 12 patients exhibited late positivity in the FCXM. In absorption studies, antibodies directed against fetal calf serum (FCS), a component of the MSC culture medium, were identified. Healthy individuals expressed varying levels of anti-FCS antibodies and the same pattern was seen in immunosuppressed HSCT patients. MSC did not express blood group antigens. The patients with positive FCXM are alive and well.


CONCLUSIONS
We have shown that immunosuppressed patients can exhibit anti-FCS antibodies, but no alloantibodies, that may bind to MSC. These antibodies seem clinically insignificant.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. mikael.sundin@ki.se
Mikael
M
Sundin
Olle
O
Ringdén
Berit
B
Sundberg
Silvia
S
Nava
Cecilia
C
Götherström
Katarina
K
Le Blanc
D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002417:Cattle; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology; D019337:Hematologic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D007223:Infant; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D017154:Stromal Cells / Q000276:immunology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D007518:Isoantibodies