Immunoregulatory networks in healthy adult allogeneic stem cell donors : Studies of peripheral hematopoietic stem cell donors and their recipients
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Final outcome after allogeneic peripheral blood stem cell transplantation (PBSCT) is influenced by the high degrees of variation in disease and comorbidities among recipients, as well as the pre-and post-transplant handling of patients. Recent studies suggest that outcome is also influenced by donor heterogeneity, and the impact of G-CSF–induced immunomodulation on graft composition and post-transplant outcome is still not fully understood. In this exploratory study, we characterized healthy HLA-matched related donors with respect to 27 distinct circulating lymphoid subsets, and systemic levels of 39 soluble mediators and 641 metabolites during hematopoietic stem cell mobilization and collection. A high degree of variation among donors was detected. This heterogeneity was further increased during G-CSF treatment and apheresis through preferential enrichment of certain immune cell subsets, soluble mediators and metabolites both in the donors and the stem cell grafts. Bioinformatics analyses were used to identify donor G-CSF–induced systemic changes and revealed a distinct dichotomy in G-CSF immune cell mobilization response, with potential impacts on recipient outcome. Our findings show that the systemic G-CSF–induced mediator profile predicted stem cell yield, and graft mediator profile was dependent on apheresis device and correlated to graft leukocyte and platelet levels. Our overall results show that healthy stem cell donors are heterogeneous with regard to immunoregulation, and this heterogeneity is increased by G-CSF treatment and stem cell harvesting. Future clinical studies should further investigate how immunological donor characteristics influence outcome after allotransplantation and the possible implications for hematopoietic stem cell mobilization and collection.
Has partsPaper I: Melve GK, Ersvaer E, Eide GE, Kristoffersen EK, Bruserud O. Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets. Front Immunol 2018;9: 845. The article is available at: http://hdl.handle.net/1956/18227
Paper II: Melve GK, Ersvaer E, Rye KP, Ahmed AB, Kristoffersen EK, Hervig T, Reikvam H, Hatfield KJ, Bruserud O. The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis. Cytotherapy 2018;20: 740-54. The article is available in the main thesis. The article is also available at: https://doi.org/10.1016/j.jcyt.2018.02.366
Paper III: Melve GK, Ersvaer E, Akkok CA, Ahmed AB, Kristoffersen EK, Hervig T, Bruserud O. Immunomodulation Induced by Stem Cell Mobilization and Harvesting in Healthy Donors: Increased Systemic Osteopontin Levels after Treatment with Granulocyte Colony-Stimulating Factor. Int J Mol Sci 2016;17: 1158. The article is available at: http://hdl.handle.net/1956/15258
Paper IV: Hatfield KJ, Melve GK, Bruserud O. Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors. Metabolomics 2017;13: 2. The article is available in the main thesis. The article is also available at: https://doi.org/10.1007/s11306-016-1139-x