Hjem
Klinisk institutt 2
Midtveisevaluering

Midtveisevaluering - Guro Kristin Melve

Hovedinnhold

Abstract: Immunoregulatory networks in donors and recipients of allogeneic peripheral stem cell grafts

 

Background: Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allografts even though the blood grafts contain more T cells, indicating mobilization-related immunoregulatory effects.

The aim of the project is to to survey the cytokine- and immune cell networks in stem cell donors and recipients, with special focus on the effects of G-CSF treatment on cytokine, immune cell and metabolomic profiles. Increased knowledge about immunomodulatory effects of G-CSF and composition of the stem cell graft may contribute to secure donor treatment and follow up, and to safer transplantation procedures for allgeneic stem cell recipients. 

Methods: The main methods used are multicolor flow cytometry to investigate cells from frozen PBMC samples, Luminex/ELISA to investigate small molecular plasma mediators (cytokines, chemokines, growth factors, adhesion molecules, matrix metalloproteases), and mass spectrometry for global metabolite analyses.  

 

Results: In paper I we show that G-CSF treatment increases systemic levels of the immunoregulatory phosphoprotein osteopontin in allogeneic stem cell donors. Compared to healthy individuals, systemic osteopontin concentration is raised in myeloma patients mobilized with G-CSF for autologous stem cell harvest and particularly in allogeneic stem cell recipients at the time of transplantation.  


In paper II we we will describe the effect of stem cell mobilization and harvest on 38 small molecular mediators. We have found a tendency towards increased plasma levels of interleukins and adhesion molecules after stem cell mobilization with G-CSF, whereas the concentration of most chemokines, growth factors and adhesion molecules decreased during leukapheresis.  

In paper III 641 metabolites were identified in serum from allogeneic stem cell donors, and based on their overall metabolic profiles, serum collected before and after G-CSF stimulation could be distinguished with 97 % predictive accuracy.

In paper IV we will focus on how the distribution and functional markers of T cells, B cells and NK cells are changed during the stem cell mobilization and harvesting process.