Pre-infusion single-dose mesenchymal stem cells promote platelet engraftment and decrease severe acute graft versus host disease without relapse in haploidentical peripheral blood stem cell transplantation
The Journal of international medical research. 2020;48(5):300060520920438
BACKGROUND Mesenchymal stem cells (MSCs) may be used to treat steroid-refractory graft versus host disease (GVHD). However, the effects of MSCs in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) have not been confirmed in randomized studies. METHODS We conducted a randomized clinical study to investigate the effects of pre-infusion (1 x 10(6) cells/kg) MSCs on hematopoietic recovery, Epstein-Barr and cytomegalovirus infection, GVHD, and relapse in patients undergoing haplo-PBSCT. Fifty patients with acute leukemia or myelodysplastic syndrome were randomly divided into an MSC group administered 1 x 10(6) MSCs/kg 4 to 6 hours before infusion of peripheral stem cells and a control group without MSCs. RESULTS Mean platelet engraftment time was significantly faster in the MSC compared with the control group (12.28 vs 13.29 days). The mean neutrophil engraftment time was comparable in both groups (10.76 +/- 2.40 vs. 10.29 +/- 1.72 days). Grade II or above acute GVHD was significantly decreased in the MSC compared with the control group (12% vs. 36%). There were no significant differences in relapse rate or overall survival between the groups. CONCLUSION These results suggest that pre-infusion single-dose MSCs promote platelet engraftment and decrease severe acute GVHD without increasing relapse rate.
Donor-derived marrow mesenchymal stromal cell co-transplantation following a haploidentical hematopoietic stem cell transplantation trail to treat severe aplastic anemia in children
Annals of hematology. 2018
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Recent studies have shown that mesenchymal stromal cells (MSCs) display potent immunosuppressive effects and can support normal hematopoiesis. In a multi-center trial, we co-transplanted culture-expanded donor-derived bone marrow MSCs (BM-MSCs) into 35 children with severe aplastic anemia (SAA) undergoing haplo-HSCT. All 35 patients (100%) achieved hematopoietic reconstitution and showed sustained full donor chimerism. The median time for myeloid engraftment was 14 days (range 10-22 days), while that for platelet engraftment was 18 days (range 9-36 days). The incidence of grade II-IV acute GVHD and chronic GVHD was 25.71 and 22.86%, respectively. The overall survival rate was 85.71% with a median of 22 months (range 3.5-37 months). The combined transplantation of haploidentical HSCs and BM-MSCs into children with SAA without an HLA-identical sibling donor is relatively safe and may represent an effective new therapy to improve survival rates and reduce the risk of graft failure.
Analysis of multipotent mesenchymal stromal cells used for acute graft-versus-host disease prophylaxis
European Journal of Haematology. 2016;96(4):425-34
BACKGROUND Multipotent mesenchymal stromal cells (MSCs) are used for prophylaxis of acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Not all samples of MSC are efficient for aGvHD prevention. The suitability of MSCs for aGvHD prophylaxis was studied. METHODS MSCs were derived from the bone marrow (BM) of HCT donor and cultivated for no more than three passages. The characteristics of donor BM samples including colony-forming unit fibroblast (CFU-F) concentration, growth parameters of MSCs, and the relative expression levels (REL) of different genes were analyzed. MSCs were injected intravenously precisely at the moment of blood cell reconstitution. RESULTS MSCs infusion induced a significant threefold decrease in aGvHD development and improved overall survival compared with the standard prophylaxis group. In ineffective MSC samples (9.4%), a significant decrease in total cell production and the REL of CSF1, FGFR1, and PDGFRB was observed. In all studied BM samples, the cumulative MSC production and CFU-F concentrations decreased with age. The expression levels of FGFR2, PPARG, and VEGF differed by age. CONCLUSIONS A universal single indicator for the prediction of MSC eligibility for aGvHD prophylaxis was not identified. A multiparameter mathematical model for selecting MSC samples effective for the prevention of aGvHD was proposed. Copyright © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.