title: Treatment of severe chronic graft-versus-host disease with decidual stromal cells and tracing with (111)indium radiolabeling.
abstract: Decidual stromal cells (DSCs) isolated from fetal membranes of term placentas are easily expanded and are highly immunosuppressive in vitro. These cells express high levels of integrins that are of importance in homing to inflamed tissues. In this study, we investigated DSCs as a cellular therapy for chronic graft-versus-host disease (cGvHD), a severe complication after allogeneic hematopoietic stem cell transplantation. Subsequent to transplantation, three patients developed severe extensive cGvHD and were treated with DSCs (1-2.8 × 10(6) cells/kg). One-third of the DSCs administered to two patients were labeled with (111)Indium, and the in vivo distribution was tracked for 48 h. The (111)In-labeled DSCs were initially located in the lungs, followed by dissemination to the liver and spleen. The DSCs induced a partial response in two of the patients. Blood samples from the patients were extensively evaluated by flow cytometry, luminex, and enzyme-linked immunosorbent assay. The nonresponder had the highest proportion of T-cells with Th17 and Th2 phenotypes and the highest median plasma concentrations of IL-17 and IL-4. The same patient also had high frequencies of HLA-DR(+) T-cells and regulatory T-cells. To conclude, DSCs are safe to infuse with no adverse effects. We determined how stromal cells are distributed in vivo after infusion in a cGvHD setting. The methods established for analysis of blood samples will be useful in determining the effect of DSCs in a study comprising a larger patient material. This pilot study may provide a basis for further controlled investigations with DSCs in a clinical setting.
authors.affiliation: 1 Division of Therapeutic Immunology, Department of Laboratory Medicine, Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet and Karolinska University Hospital , Stockholm, Sweden .
authors.forename: Tom
authors.initials: T
authors.lastname: Erkers
authors.forename: Helen
authors.initials: H
authors.lastname: Kaipe
authors.forename: Silvia
authors.initials: S
authors.lastname: Nava
authors.forename: Pia
authors.initials: P
authors.lastname: Molldén
authors.forename: Britt
authors.initials: B
authors.lastname: Gustafsson
authors.forename: Rimma
authors.initials: R
authors.lastname: Axelsson
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D064591:Allografts; D058948:Cell Tracking; D002908:Chronic Disease; D003656:Decidua; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007204:Indium / Q000008:administration & dosage*; D007554:Isotopes / Q000008:administration & dosage; D007938:Leukemia / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy; D039902:Multipotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D007554:Isotopes; D007204:Indium