Fetal Membrane Cells for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease§

Authors

  • Olle Ringdén,

    Corresponding author
    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
    • Division of Therapeutic Immunology, F79, Dept. of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
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    • Telephone: +46 8 585 82672; Fax: +46 8 7466699

  • Tom Erkers,

    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Silvia Nava,

    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Mehmet Uzunel,

    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Erik Iwarsson,

    1. Department of Clinical GeneticsKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
    2. Department of Molecular Medicine and SurgeryKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Réka Conrad,

    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Magnus Westgren,

    1. Department of Obstetrics and Gynecology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Jonas Mattsson,

    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Helen Kaipe

    1. Division of Therapeutic Immunology, Department of Laboratory Medicine, and Center for Allogeneic Stem Cell TransplantationKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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  • Author contributions: O.R.: concept and design, financial support, administrative support, provision of study material or patients, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.E.: concept and design, provision of study material or patients, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; S.N.: provision of study material or patients, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; M.U. and E.I.: provision of study material or patients, collection and/or assembly of data, data analysis and interpretation, and final approval of manuscript; R.C.: provision of study material or patients, collection and/or assembly of data, and final approval of manuscript; M.W.: provision of study material or patients and final approval of manuscript; J.M.: provision of study material or patients, data analysis and interpretation, and final approval of manuscript; H.K.: concept and design, financial support, provision of study material or patients, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS January 10, 2013.

Abstract

The placenta protects the fetus from the mother's immune system. We have previously found that fetal membrane cells (FMCs) isolated from term placenta prevent alloreactivity in vitro. FMCs share many features with bone marrow-derived mesenchymal stromal cells (MSCs), which we previously introduced to treat severe acute graft-versus-host disease (GVHD). Here, we tested FMCs for treatment of steroid-refractory acute GVHD. After two passages in culture, approximately 109 FMCs were obtained from one single placenta, although not all cells from passage 0 and passage 1 were used for expansion. The FMCs were positive for CD29, CD44, CD73, CD90, CD105, and CD49d but were negative for hematopoietic, endothelial, and epithelial markers. Microsatellite polymorphism analysis showed that FMCs were of maternal origin. All FMCs used showed normal karyotype. Nine patients who had undergone hematopoietic stem cell transplantation (HSCT) and who had developed steroid-refractory grade III–IV acute GVHD were given 0.9–2.8 × 106 FMCs per kg at 15 infusions. Median age was 57 years. There was no toxicity from infusion of FMCs in eight patients. One patient had seizures after infusion. Two of eight evaluable patients had a complete response and four had a partial response, giving an overall response rate of 75%. Two patients showed no response at all. Three patients are alive from 6 to 21 months after HSCT. One patient is well and two have chronic GVHD. Thus, FMCs may be successfully used for immune modulation and tissue repair. STEM CELLS2013;31:592–601

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