Immunophenotypic characteristics of multipotent mesenchymal stromal cells that affect the efficacy of their use in the prevention of acute graft vs host disease  

作　　者：Nataliya Petinati Nikolay Kapranov Yulia Davydova Alexey Bigildeev Olesya Pshenichnikova Dmitriy Karpenko Nina Drize Larisa Kuzmina Elena Parovichnikova Valeriy Savchenko 

机构地区：[1]Laboratory for Physiology of Hematopoiesis,National Research Center for Hematology,Moscow 125167,Russia [2]Laboratory for Immunophenotyping of Blood and Bone Marrow Cells,National Research Center for Hematology,Moscow 125167,Russia [3]Laboratory for Genetic Engineering,National Research Center for Hematology,Moscow 125167,Russia [4]Hematopoiesis Depression and Bone Marrow Transplantation Department,National Research Center for Hematology,Moscow 125167,Russia

出　　处：《World Journal of Stem Cells》2020年第11期1377-1395,共19页世界干细胞杂志（英文版）（电子版）

摘　　要：BACKGROUND Multipotent mesenchymal stromal cells(MSCs)are widely used in the clinic due to their unique properties,namely,their ability to differentiate in all mesenchymal directions and their immunomodulatory activity.Healthy donor MSCs were used to prevent the development of acute graft vs host disease(GVHD)after allogeneic bone marrow transplantation(allo-BMT).The administration of MSCs to patients was not always effective.The MSCs obtained from different donors have individual characteristics.The differences between MSC samples may affect their clinical efficacy.AIM To study the differences between effective and ineffective MSCs.METHODS MSCs derived from the bone marrow of a hematopoietic stem cells donor were injected intravenously into allo-BMT recipients for GVHD prophylaxis at the moment of blood cell reconstitution.Aliquots of 52 MSC samples that were administered to patients were examined,and the same cells were cultured in the presence of peripheral blood mononuclear cells(PBMCs)from a third-party donor or treated with the pro-inflammatory cytokines IL-1β,IFN and TNF.Flow cytometry revealed the immunophenotype of the nontreated MSCs,the MSCs cocultured with PBMCs for 4 d and the MSCs exposed to cytokines.The proportions of CD25-,CD146-,CD69-,HLA-DR-and PD-1-positive CD4+and CD8+cells and the distribution of various effector and memory cell subpopulations in the PBMCs cocultured with the MSCs were also determined.RESULTS Differences in the immunophenotypes of effective and ineffective MSCs were observed.In the effective samples,the mean fluorescence intensity(MFI)of HLAABC,HLA-DR,CD105,and CD146 was significantly higher.After MSCs were treated with IFN or cocultured with PBMCs,the HLA-ABC,HLA-DR,CD90 and CD54 MFI showed a stronger increase in the effective MSCs,which indicated an increase in the immunomodulatory activity of these cells.When PBMCs were cocultured with effective MSCs,the proportions of CD4+and CD8+central memory cells significantly decreased,and the proportion of CD8+CD146+lymphocytes in

关 键 词：Multipotent mesenchymal stromal cells Acute graft vs host disease IMMUNOPHENOTYPE LYMPHOCYTES IMMUNOMODULATION Pro-inflammatory cytokines 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]