No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients

From the Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, SE-141 86 Stockholm, Sweden (MS, OR, BS, SN, CG, KLB); Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden (OR); Hematology Center, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden (KLB) Correspondence: Mikael Sundin, M.D., Division of Clinical Immunology, F79, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. E-mail: mikael.sundin{at}ki.se Background and Objectives: 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 HLA matched or mismatched allogeneic MSC. Design and 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. Interpretation and Conclusions: We have shown that immunosuppressed patients can exhibit anti-FCS antibodies, but no alloantibodies, which may bind to MSC. These antibodies seem clinically insignificant. Key words: rejection, humoral, immunogenicity, cross match.