Original Article
Leukemia (2007) 21, 2271–2276; doi:10.1038/sj.leu.2404833; published online 5 July 2007
Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon
O Ringdén1,2, M Uzunel2, B Sundberg2, L Lönnies2, S Nava2, J Gustafsson3, L Henningsohn4 and K Le Blanc1,2
- 1Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
- 2Division of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
- 3Department of Radiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
- 4Department of Urology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
Correspondence: Professor O Ringdén, Division of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital Huddinge, F79, SE-141 86 Stockholm, Sweden. E-mail: Olle.Ringden@ki.se
Received 3 May 2007; Revised 22 May 2007; Accepted 1 June 2007; Published online 5 July 2007.
Abstract
Mesenchymal stem cells (MSC) possess anti-inflammatory properties and participate in tissue repair. We used MSC to heal therapy-induced tissue toxicity. Ten consecutive patients, treated with MSC due to tissue toxicity following allogeneic hematopoietic stem cell transplantation, (ASCT) were included. Their median age was 48 (13–64) years. Seven had hemorrhagic cystitis grades 2–5, two had pneumomediastinum and one had perforated colon and peritonitis. MSC donors were mainly third-party, HLA-mismatched (n=11), HLA-haploidentical (n=3) and, in two cases, the HLA-identical ASCT sibling donors. MSC were given intravenously, the median cell dose was 1.0 (range 0.7–2)
106/kg. In five patients, the severe hemorrhagic cystitis cleared after MSC infusion. Gross hematuria disappeared after median 3 (1–14) days. Two patients had reduced transfusion requirements after MSC infusion, but died of multiorgan failure. In one of them, MSC donor DNA was demonstrated in the urinary bladder. In two patients, pneumomediastinum disappeared after MSC infusions. A patient with steroid-resistant graft-versus-host disease of the gut experienced perforated diverticulitis and peritonitis that was reversed twice by MSC. MSC is a novel treatment for therapy-induced tissue toxicity.
Keywords:
mesenchymal stem cells, allogeneic hematopoietic stem cell, transplantation, hemorrhagic cystitis, pneumomediastinum, colon perforation
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