Xenogeneic immunosuppression of human umbilical cord mesenchymal stem cells in a major histocompatibility complex-mismatched allogeneic acute graft-versus-host disease murine model

2011 ◽  
Vol 87 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Juan Guo ◽  
Jie Yang ◽  
Guofan Cao ◽  
Huahua Fan ◽  
Chenzhi Guo ◽  
...  
Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4536-4536
Author(s):  
Guanghua Chen ◽  
Ting Yang ◽  
Chengcheng Fu ◽  
Miao Miao ◽  
Zhengming Jin ◽  
...  

Abstract Abstract 4536 Objective To evaluate the safety profile and efficacy of umbilical cord-derived mesenchymal stem cell infusion in patients with steroid-resistant, severe, acute graft-versus-host disease (aGVHD). Methods A total of 19 patients with steroid-resistant severe aGVHD received mesenchymal stem cell infusion treatment. We analyzed the treatment response, transplantation-related mortality, events associated with infusion and relapse rate. Results Two patients with grade II, 5 patients with grade III and 12 patients with grade ‡W aGVHD received a total of 58 infusions of mesenchymal stem cell. The mean total dose of mesenchymal stem cell was 2.13×106 (range 0.6–7.2×106) cells per kg bodyweight. 7 patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. 11 patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions of mesenchymal stem cell and no ectopic tissue was detected to date. 11 patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared mesenchymal stem cell is 93% (92%-95%) by trypan blue staining. The cell viability of controlled-rate freezed and thawed cells mesenchymal stem cell is 72% (70%-74%). Conclusion Infusion of umbilical cord-derived mesenchymal stem cell expanded in vitro is an effective therapy for patients with steroid-resistant, severe aGVHD without negative impact on relapse. Freshly prepared mesenchymal stem cells are superior to freezed and thawed cells in terms of cell viability. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Weijiang Liu ◽  
Na Zhou ◽  
Peng Wang ◽  
Yuanlin Liu ◽  
Wei Zhang ◽  
...  

Abstract Background Mesenchymal stem cells (MSCs) have been utilized in treating acute graft-versus-host disease (aGvHD) as they show strong immunosuppressive capacity, but the mechanisms are not well defined.Methods In this study, we demonstrated that microRNA-223 (miR-223) derived from exosomes secreted by human umbilical cord mesenchymal stem cells (huc-MSCs) and murine compact bone mesenchymal stem cells (mb-MSCs) could inhibit aGvHD progression by reducing the migration and homing of donor T cells in aGvHD mice.Results MiR-223 was one of the conserved microRNAs highly expressed in huc-MSCs exosomes and mMSCs exosomes, which was identified by high-throughput sequencing. MiR-223 derived from MSC exosomes showed enhanced immunosuppressive capacity, as it could inhibit expression of the target gene ICAM-1 and restrain adhesion and migration of T cells in vitro. Moreover, miR-223Agomir was effective in reducing the inflammatory reaction, and declining the donor T cells infiltration into the spleen, liver and intestine in aGvHD mice. Subsequently, it could alleviate aGvHD symptoms. Taken together, the MSC exosome derived miR-223 could attenuate aGvHD in mice through regulating ICAM-1 expression.Conclusions Our results unveil a new role for MSC exosomes derived miR-223 in the treatment of aGvHD.


Sign in / Sign up

Export Citation Format

Share Document