***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Success of umbilical cord blood transplantation ( UCBT ) has been limited by a high rate of graft failure and delayed hematological recovery . It has been postulated that MSCs have hematopoiesis-supportive properties . Therefore , to overcome the limitation of UCBT , third-party UCB-derived MSCs were co-transplanted in recipients receiving unrelated UCBT . Seven patients received UCB and third-party UCB – MSCs .  Hematopoietic recovery and transplantation outcomes were compared with historic controls . There was no acute toxicity associated with the infusion of MSCs . The median day to neutrophil engraftment was 19 days in patients , as compared with 24 days in controls ( P=0.03 ) . The median day of platelet engraftment was 47 days and 57 days in patients and controls , respectively ( P=0.26 ) . In addition , there was no engraftment failure in the MSC group . The incidence of acute and chronic GVHD was comparable between the two groups . However , veno-occlusive disease and TRM did not occur in the MSC group . Third-party UCB – MSCs infusion was safe and feasible . MSCs may also enhance the engraftment of UCBT and prevent rejection . In addition , MSCs may have a role in decreasing TRM . R and omized , controlled trials are required to confirm these results and longer follow-up will determine the effects of MSCs on the risk of relapse Suboptimal neutrophil and platelet recovery after unrelated donor umbilical cord blood transplantation ( UCBT ) may be due in part to an impaired microenvironment after intensive chemoradiotherapy . In an attempt to speed hematopoietic recovery , 15 pediatric patients with high-risk acute leukemia were enrolled on a single-institution phase I – II clinical trial in which ex-vivo culture-exp and ed MSCs from haploidentical parental donors were infused at the time of UCBT . Eight patients received MSCs on day 0 , with three patients having a second dose infused on day 21 . No serious adverse events were observed with any MSC infusion . All eight evaluable patients  achieved neutrophil engraftment at a median of 19 days . Probability of platelet engraftment was 75 % , at a median of 53 days . With a median follow-up of 6.8 years , five patients remain alive and disease free . The results of this pilot study show that infusion of ex-vivo culture-exp and ed haploidentical MSCs into unrelated pediatric UCBT recipients can be performed safely . This encouraging safety profile with haploidentical MSCs supports the investigation of unrelated ‘ off the shelf ’ allogeneic HLA-mismatched MSC products The unique immunomodulatory properties of mesenchymal stem cells ( MSCs ) make them a rationale agent to investigate for graft-versus-host disease ( GVHD ) . Human MSCs were used to treat de novo acute GVHD ( aGVHD ) . Patients with grade s II-IV GVHD were r and omized to receive 2 treatments of human MSCs ( Prochymal(R ) ) at a dose of either 2 or 8 million MSCs/kg in combination with corticosteroids . Patients received GVHD prophylaxis with tacrolimus , cyclosporine , ( CsA ) or mycophenolate mofetil ( MMF ) . Study endpoints included safety of Prochymal administration , induction of response to Prochymal , and overall response of aGVHD by day 28 , and long-term safety .  Thirty-two patients were enrolled , with 31 evaluable : 21 males , 10 females ; median age 52 years ( range : 34 - 67 ) . Twenty-one patients had grade II , 8 had grade III , and 3 had grade IV aGVHD . Ninety-four percent of patients had an initial response to Prochymal ( 77 % complete response [ CR ] and 16 % partial response [ PR ] ) . No infusional toxicities or ectopic tissue formations were reported . There was no difference with respect to safety or efficacy between the low and high Prochymal dose . In conclusion , Prochymal can be infused safely into patients with aGVHD and induces response in a high proportion of GVHD patients Mesenchymal stromal cells ( MSCs ) possess a multi-lineage potential and immunoregulatory activities and provide a great potential in cell-based technologies . However , MSC suppressive activity raises concerns regarding the possible adverse effect of MSCs on the immune recovery . The influence of autologous MSC co-transplantation on recovery of T cell subsets in patients receiving autologous hematopoietic stem cell transplantation ( AHSCT ) for malignant lymphomas and multiple myeloma were characterized . Co-transplantation of MSCs improved lymphocyte recovery most effectively in patients with low input of hematopoietic stem cells or low absolute lymphocyte count in apheresis product . MSC co-transplantation improved early recovery of both memory and naive T cells with more prominent effect on naive CD4(+ ) T cells .  Patients with  MSC co-transplantation  showed more effective reconstitution of recent thymic emigrants . These data indicate the positive impact of MSCs on immune reconstitution and note MSC co-transplantation is feasible to optimize the outcomes of AHSCT in malignant lymphoma patients Engraftment failure ( EF ) after autologous hematopoietic stem cell transplantation is a serious complication . We prospect ively evaluated the effects and safeties of mesenchymal stem cells ( MSCs ) alone and MSCs combined with cord blood ( CB ) for EF . Twenty-two patients were r and omized to receive MSCs ( MSC group ; n = 11 ) or  MSCs plus CB ( CB group ; n = 11 ) . Patients with no response ( NR ) to MSCs  received the therapeutic schedule in the CB group , and those patients with partial response ( PR ) in the MSC group and patients without complete remission ( CR ) in the CB group received another cycle of MSC treatment . Patients who did not achieve CR after 2 cycles of treatments received other treatments , including allogeneic HSCT . After the first treatment cycle , response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group ( P = .635 ) , with a significant difference in neutrophil reconstruction between the 2 groups ( P = .030 ) . After 2 treatment cycles , 16 patients achieved CR , 3 achieved PR , and 3 had NR . No patient experienced graft-versus-host disease ( GVHD ) . With a median follow-up of 345 d ( range , 129 to 784 d ) post-transplantation , 18 patients remained alive and 4 had died ( 3 from primary disease relapse and 1 from cytomegalovirus pneumonia ) . The 2-year overall survival , disease-free survival , and cumulative incidence of tumor relapse post-transplantation were 75.2 % ± 12.0 % , 79.5 % ± 9.4 % , and 20.5 % ± 9.4 % , respectively . Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse , but the MSC plus CB regimen has a superior effect on neutrophil reconstruction The efficacy and the safety of the administration of multipotent mesenchymal stromal cells ( MMSCs ) for acute graft-versus-host disease ( aGVHD ) prophylaxis following allogeneic hematopoietic cell transplantation ( HSCT ) were studied . This prospect i ve clinical trial was based on the r and om patient allocation to the following two groups receiving ( 1 ) st and ard GVHD prophylaxis and ( 2 ) st and ard GVHD prophylaxis combined with MMSCs infusion . Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9–1.3 × 106/kg when the blood counts indicated recovery . aGVHD of stage II – IV developed in 38.9 % and 5.3 % of patients in group 1 and group 2 , respectively , ( P = 0.002 ) . There were no differences in the graft rejection rates , chronic GVHD development , or infectious complications . Overall mortality was 16.7 % for patients in group 1 and 5.3 % for patients in group 2 .  The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study BACKGROUND AIMS Despite the efficacy of allogeneic hematopoietic stem cell transplantation ( allo-HSCT ) , the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease ( GvHD ) .  Mesenchymal stromal cells ( MSCs ) are a new mode of therapy in the context of allo-HSCT . The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs ( AT-MSCs ) in patients with chronic GvHD . METHODS Fourteen patients with moderate ( n = 7 ) or severe ( n = 7 ) chronic GvHD received 1 × 106/kg ( group A , n = 9 ) or 3 × 106/kg ( group B , n = 5 ) AT-MSCs with cyclosporine and prednisone as first-line therapy . RESULTS Ten of the 14 patients were able to continue under the protocol : 80 % were in complete remission , and 100 % were off of steroids at week 56 . The remaining 4 patients either worsened from chronic GvHD ( n = 3 ) or ab and oned the study ( n = 1 ) . At the end of the study , 11 of 14 patients are alive ( overall survival 71.4 % , median survival of 45.3 weeks ) . No suspected unexpected serious adverse reactions occurred during the trial . Neither relapse of underlying disease nor mortality due to infection was observed in this cohort . Biological studies showed increased CD19 , CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells . DISCUSSION AT-MSCs , in combination with immunosuppressive therapy , may be considered feasible and safe and likely would have an impact on the course of chronic GvHD . More studies are warranted to underst and the potential benefits of AT-MSCs in these patients Mesenchymal stem cells ( MSCs ) are found in a variety of tissues , including human bone marrow ; secrete hematopoietic cytokines ; support hematopoietic progenitors in vitro ; and possess potent immunosuppressive properties . We hypothesized that cotransplantation of culture-exp and ed MSCs and hematopoietic stem cells ( HSCs ) from HLA-identical sibling donors after myeloablative therapy could facilitate engraftment and lessen graft-versus-host disease ( GVHD ) ; however , the safety and feasibility of this approach needed to be established . In an open-label , multicenter trial , we coadministered culture-exp and ed MSCs with HLA-identical sibling-matched HSCs in hematologic malignancy patients . Patients received either bone marrow or peripheral blood stem cells as the HSC source . Patients received 1 of 4 study -specified transplant conditioning regimens and methotrexate ( days 1 , 3 , and 6 ) and cyclosporine as GVHD prophylaxis . On day 0 , patients were given culture-exp and ed MSCs intravenously ( 1.0 - 5.0 x 10(6)/kg ) 4 hours before infusion of either bone marrow or peripheral blood stem cells . Forty-six patients ( median age , 44.5 years ; range , 19 - 61 years ) received MSCs and HLA-matched sibling allografts . MSC infusions were well tolerated , without any infusion-related adverse events . The median times to neutrophil ( absolute neutrophil count > or = 0.500 x 10(9)/L ) and platelet ( platelet count > or = 20 x 10(9)/L ) engraftment were 14.0 days ( range , 11.0 - 26.0 days ) and 20 days ( range , 15.0 - 36.0 days ) , respectively . Grade II to IV acute GVHD was observed in 13 ( 28 % ) of 46 patients . Chronic GVHD was observed in 22 ( 61 % ) of 36 patients who survived at least 90 days ; it was extensive in 8 patients . Eleven patients ( 24 % ) experienced relapse at a median time to progression of 213.5 days ( range , 14 - 688 days ) . The probability of patients attaining disease- or progression-free survival at 2 years after MSC infusion was 53 % . Cotransplantation of HLA-identical sibling culture-exp and ed MSCs with an HLA-identical sibling HSC transplant is feasible and seems to be safe , without immediate infusional or late MSC-associated toxicities . The optimal MSC dose and frequency of administration to prevent or treat GVHD during allogeneic HSC transplantation should be evaluated further in phase II clinical trials BACKGROUND Severe graft-versus-host disease ( GVHD ) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells .  Mesenchymal stem cells modulate immune responses in vitro and in vivo . We aim ed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation . METHODS Patients with steroid-resistant , severe , ac 
    Output:
    
MSCs  were well-tolerated , no infusion-related toxicity or ectopic tissue formation was reported .
Despite a number of reports of positive outcomes from the use of MSCs for treating acute GvHD , the evidence to date from RCTs has not supported the conclusion that they are an effective therapy .
There is low- quality evidence that MSCs may reduce the risk of cGvHD .