No abstract

MSC is a very promising treatment for severe steroid-resistant acute GVHD.

Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to <1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a “hit and run” mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy.

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)x10(6)/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.