Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon

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)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.

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

“…The patient's disturbed hemostasis and systemic vasodilatation may not only have caused the extensive microembolization and macroembolization observed in the lungs but may also explain the wide distribution of the MSCs. In one patient (1033), the extrapulmonary finding of MSC donor DNA correlated with the known intestine and bladder sites of injury, but no general tendency of homing to damaged tissue was found in this material [15].…”

“…The first method, a nested PCR described previously [15], is nonquantitative and was used in three patients (917, 924, and 1033). Primers were designed based on differences in the HLA type between the MSC donors, the patients, and the HSCT donors.…”

Stromal cells–are they really useful for GVHD?

“…101 Stromal cells have a profound effect on coagulation, 18,20 which partly explains their effectiveness in stopping major hemorrhages. 90,102,103 BM must be accessed by aspiration, and this source of MSCs has been challenged by MSCs from adipose tissue, umbilical-cordderived MSCs and stromal cells from the placenta-such as DSCs. Placental stromal cells are accessible without any invasive procedure and with little ethical consideration.…”

Transplantation of Single Mismatch Hematopoietic Stem Cells with Third Party Mesenchymal Stem Cells for Severe Aplastic Anemia: A Case Report and Mini Review

“…With the support of MSCs successful results were obtained for patients with hemorrhagic cystitis whose treatment are complicated by colon perforation [9]. Some health centers think that MSCs may prove insufficient to avoid toxicity mediated by cytotoxic T cells, therefore it has been suggested that MSCs must be combined with systemic immunosuppressive therapy to provide adequate T cell suppression [14].…”

“…MSCs can help improve tissue toxicity associated with allo-HSCT, by repairing the damaged tissue. MSCs also promise good results for the treatment of GVHD associated with HSCT [9,10].…”