Published online Nov 26, 2020. doi: 10.4252/wjsc.v12.i11.1377
Peer-review started: May 28, 2020
First decision: July 30, 2020
Revised: July 31, 2020
Accepted: September 1, 2020
Article in press: September 1, 2020
Published online: November 26, 2020
Processing time: 178 Days and 1.9 Hours
Multipotent mesenchymal stromal cells (MSCs) are widely used in the clinic due to their unique properties, namely, their immunomodulatory activity. Healthy donor MSCs were used to prevent the development of 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.
It is necessary to increase the efficiency of MSCs use for GVHD prevention after allo-BMT.
The present study aimed to identify the differences between effective and ineffective MSCs.
Aliquots of 52 MSC samples that were used for GVHD prophylaxis were examined. These 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. The immunophenotype of untreated MSCs, the MSCs cocultured with PBMCs for 4 days or the MSCs exposed to cytokines was investigated by flow cytometry. 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 MSCs were also determined.
Differences in the immunophenotypes of effective and ineffective MSCs were observed. In the effective samples, the mean fluorescence intensity (MFI) of HLA-ABC, 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 increased more than in the subpopulations of lymphocytes cocultured with MSC samples that were ineffective in GVHD prevention. In addition, the proportion of CD8+effector memory lymphocytes decreased in the PBMCs cocultured with the effective MSC samples but increased in the PBMCs cocultured with the ineffective MSC samples. The proportion of CD4+CD146+ lymphocytes increased only when cocultured with the inefficient samples.
For the first time, differences were observed between MSC samples that were effective for GVHD prophylaxis and those that were ineffective. Thus, it was shown that the immunomodulatory activity of MSCs depends on the individual characteristics of the MSC population.
Determination of the main differences between effective and ineffective samples will improve the clinical results of MSCs use. The list of the most significant parameters showing the differences between effective and ineffective MSC samples may change after increasing the number of samples and additional analysis of samples using OMIX technology.