title: Immunogenicity of decidual stromal cells in an epidermolysis bullosa patient and in allogeneic hematopoietic stem cell transplantation patients.
abstract: Allogeneic mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but little is known about their immunogenicity. In this study, we monitored the therapeutic and immunogenic effects of decidual stromal cells (DSCs) from term placentas when used as a therapy for generalized severe junctional epidermolysis bullosa (JEB) (previously termed Herlitz JEB), a lethal condition caused by the lack of functional laminin-332. An 11-month-old JEB patient was treated with five infusions of allogeneic DSCs within a 3-month period. Amniotic membranes (AMs) were applied to severe wounds. After the treatment, wounds started to heal in the middle of the blisters, but the improvements were transient. After two infusions of DSCs, the JEB patient had developed multispecific anti-HLA class-I antibodies. No antibodies to laminin-332 were detected, but the patient had high levels of anti-bovine serum albumin antibodies, which could bind to DSCs. Peripheral blood mononuclear cells (PBMCs) from the patient had a higher proliferative response to DSCs than to third-party PBMCs, which contrasts with the pattern observed in healthy donors. Human DSCs and MSCs induced similar xenoreactivity in mice. Two of 16 allogeneic stem cell-transplanted patients, treated with DSCs for graft-versus-host disease or hemorrhagic cystitis, showed a positive flow cytometric crossmatch test. One patient had anti-HLA antibodies before DSC infusion, whereas the other had no anti-HLA antibodies at any time. AM and DSC infusions may have improved the healing process in the JEB patient, but DSCs appeared to induce anti-HLA antibodies. The risk of alloimmunization by DSCs seems to be low in immunocompromised patients.
authors: 1Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|2Clinical Immunology and Transfusion Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: Helen
authors: H
authors: Kaipe
authors: 3Hematology/Immunology/HSCT Section, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
authors: Lena-Maria
authors: LM
authors: Carlson
authors: 1Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Tom
authors: T
authors: Erkers
authors: 1Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Silvia
authors: S
authors: Nava
authors: 1Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Pia
authors: P
authors: Molldén
authors: 4Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.|5Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
authors: Britt
authors: B
authors: Gustafsson
authors: 6Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
authors: Hua
authors: H
authors: Qian
authors: 6Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
authors: Xiaoguang
authors: X
authors: Li
authors: 6Department of Dermatology, Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology, Kurume, Japan.
authors: Takashi
authors: T
authors: Hashimoto
authors: 1Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Behnam
authors: B
authors: Sadeghi
authors: 2Clinical Immunology and Transfusion Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: Mats
authors: M
authors: Alheim
authors: 1Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|4Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors: Olle
authors: O
authors: Ringdén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000097:blood / Q000276:immunology; D002648:Child; D003656:Decidua / Q000276:immunology / Q000637:transplantation; D004820:Epidermolysis Bullosa / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D064593:Heterografts / Q000276:immunology; D006801:Humans; D055261:Immunogenetic Phenomena; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D059630:Mesenchymal Stem Cells / Q000276:immunology; D051379:Mice; D008875:Middle Aged; D012710:Serum Albumin, Bovine / Q000276:immunology; D000097794:Kalinin
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D012710:Serum Albumin, Bovine; D000097794:Kalinin