当前位置: X-MOL 学术STEM CELLS › 论文详情
Functional dosing of mesenchymal stromal cell-derived extracellular vesicles for the prevention of acute graft-versus-host-disease.
STEM CELLS ( IF 5.614 ) Pub Date : 2020-02-17 , DOI: 10.1002/stem.3160
Giada Dal Collo,Annalisa Adamo,Alessandro Gatti,Edoardo Tamellini,Riccardo Bazzoni,Paul Takam Kamga,Cristina Tecchio,Francesca Maria Quaglia,Mauro Krampera

Graft-vs-host-disease (GvHD) is currently the main complication of allogeneic hematopoietic stem cell transplantation. Mortality and morbidity rates are particularly high, especially in steroid-refractory acute GvHD (aGvHD). Immune regulatory human bone marrow mesenchymal stromal cells (hMB-MSCs) represent a therapeutic approach to address this issue. Unfortunately, their effect is hardly predictable in vivo due to several variables, that is, MSC tissue origin, concentration, dose number, administration route and timing, and inflammatory status of the recipient. Interestingly, human bone marrow MSC-derived extracellular vesicles (hBM-MSC-EVs) display many of the hBM-MSC immunoregulatory properties due to their content in paracrine factors that greatly varies according to the collection method. In this study, we focused on the immunological characterization of hBM-MSC-EVs on their capability of inducing regulatory T-cells (T-regs) both in vitro and in a xenograft mouse model of aGvHD. We correlated these data with the aGvHD incidence and degree following hBM-MSC-EV intravenous administration. Thus, we first quantified the EV immunomodulation in vitro in terms of EV immunomodulatory functional unit (EV-IFU), that is, the lowest concentration of EVs leading in vitro to at least threefold increase of the T-regs compared with controls. Second, we established the EV therapeutic dose in vivo (EV-TD) corresponding to 10-fold the in vitro EV-IFU. According to this approach, we observed a significant improvement of both mouse survival and control of aGvHD onset and progression. This study confirms that EVs may represent an alternative to whole MSCs for aGvHD prevention, once the effective dose is reproducibly identified according to EV-IFU and EV-TD definition.
更新日期:2020-02-18

 

全部期刊列表>>
宅家赢大奖
向世界展示您的会议墙报和演示文稿
全球疫情及响应:BMC Medicine专题征稿
新版X-MOL期刊搜索和高级搜索功能介绍
化学材料学全球高引用
ACS材料视界
x-mol收录
自然科研论文编辑服务
南方科技大学
南方科技大学
西湖大学
中国科学院长春应化所于聪-4-8
复旦大学
课题组网站
X-MOL
深圳大学二维材料实验室张晗
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug