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

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World Journal of Stem Cells 2020年第11期12卷 1377-1395页

作者： Nataliya Petinati Nikolay Kapranov Yulia Davydova Alexey Bigildeev Olesya Pshenichnikova Dmitriy Karpenko nina drize Larisa Kuzmina Elena Parovichnikova Valeriy Savchenko Laboratory for Physiology of Hematopoiesis National Research Center for HematologyMoscow 125167Russia Laboratory for Immunophenotyping of Blood and Bone Marrow Cells National Research Center for HematologyMoscow 125167Russia Laboratory for Genetic Engineering National Research Center for HematologyMoscow 125167Russia Hematopoiesis Depression and Bone Marrow Transplantation Department National Research Center for HematologyMoscow 125167Russia

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 *** 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 *** MSCs obtained from different donors have individual *** differences between MSC samples may affect their clinical *** To study the differences between effective and ineffective *** 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 *** 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 *** cytometry revealed the immunophenotype of the nontreated MSCs,the MSCs cocultured with PBMCs for 4 d and the MSCs exposed to *** 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 *** Differences in the immunophenotypes of effective and ineffective MSCs were *** the effective samples,the mean fluorescence intensity(MFI)of HLAABC,HLA-DR,CD105,and CD146 was significantly *** 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 *** PBMCs were cocultured with effective MSCs,the proportions of CD4+and CD8+central memory cells significantly decreased

关键词： Multipotent mesenchymal stromal cells Acute graft vs host disease Immunophenotype Lymphocytes Immunomodulation Pro-inflammatory cytokines

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Hierarchy of mesenchymal stem cells: Comparison of multipotentmesenchymal stromal cells with fibroblast colony forming units

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Journal of Biomedical Science and Engineering 2013年第8期6卷 66-73页

作者： Irina N. Shipounova Natalia A. Petinati Alexey E. Bigildeev Natalia V. Sats nina J. drize Larisa A. Kuzmina Elena N. Parovichnikova Valery G. Savchenko Bone Marrow Transplantation Department FGBI National Hematological Scientific Center Moscow Russia Laboratory for Physiology of Hematopoiesis FGBI National Hematological Scientific Center Moscow Russia

The organization of the compartment of mesenchymal stem cells is still obscure. Two types of human stromal precursor cells are known. Both of them are analyzed in in vitro system: mesenchymal multipotent stromal cells (MMSC) and fibroblast colony forming units (CFU-F). The aim of this study was to compare the main characteristics of MMSC and CFU-F derived from the bone marrow of 24 healthy donors. Growth and differentiation parameters, as well as relative expression levels of different genes were analyzed in MMSC and CFU-F. MMSC were cultivated for 5 passages. CFU-F concentration was determined for each bone marrow sample. The data obtained demonstrated the heterogeneity and hierarchical organization of both studied populations of stromal precursor cells-MMSC and CFU-F. These two types of stromal precursor cells turned to be different in most parameters studied. Altogether MMSC seemed to be more immature cells than CFU-F and took up the higher position in hierarchical tree of mesenchymal stem cells. The rate of differentiation and proliferative potential decreased with the donor’s age in both populations MMSC and CFU-F.

关键词： Mesenchymal Multipotent Stromal Cells (MMSC) Fibroblast Colony Forming Units (CFU-F) Real-Time Polymerase Chain Reaction Gene Expression Level Aging

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