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

Track: BMT Tandem "Scientific" Meeting
Friday, February 15, 2013, 10:30 AM-12:00 PM
Ballroom E-H (Salt Palace Convention Center)
Olle Ringden, MD, PhD , Division of Therapeutic Immunology and Center for Allogeneic Stem Cell Transplantation, Karolinska. Institutet, Stockholm, Sweden
Tom Erkers, MSc , Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden
Silvia Nava, BSc , Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden
Mehmet Uzunel, MD, PhD , Clinical Immunology, Karolinska University Hospital, Stockholm, Sweden
Erik Iwarsson, MD , Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Réka Conrad, PhD , Division of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden
Magnus Westgren, MD, PhD , Dept. of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden
Jonas Mattsson, MD PhD , Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, ., Sweden
Helen Kaipe, PhD , Div. of Therapeutic Immunology, Karolinska Institutet, Stockholm, Sweden
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 and who had developed steroid-refractory grade III–IV acute GVHD were given 0.9–2.8 x 106 FMCs/kg at 15 infusions. Median age was 57 years. There was no toxicity from infusion of FMCs. Two of eight evaluable patients had a complete response and four had a partial response, giving an overall response rate of 75%. Three patients are alive from 6 to 21 months after HSCT. One patient is well and two have chronic GVHD. Two patients showed no response at all.

Thus, FMCs may be successfully used for immune modulation and tissue repair.

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