The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis

Cytotherapy. 2018 May;20(5):740-754. doi: 10.1016/j.jcyt.2018.02.366. Epub 2018 Mar 22.

Abstract

Background: Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation.

Methods: Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis.

Results: Donors could be classified into two main subsets based on their plasma mediator profile before G-CSF treatment. Seventeen of 36 detectable mediators were significantly altered by G-CSF; generally an increase in mediator levels was seen, including pro-inflammatory cytokines, soluble adhesion molecules and proteases. Several leukocyte- and platelet-released mediators were increased during apheresis. Both plasma and graft mediator profiles were thus altered and showed correlations to graft concentrations of leukocytes and platelets; these concentrations were influenced by the apheresis device used. Finally, the mediator profile of the allotransplant recipients was altered by graft infusion, and based on their day +1 post-transplantation plasma profile our recipients could be divided into two major subsets that differed in overall survival.

Discussion: G-CSF alters the short-term plasma mediator profile of healthy stem cell donors. These effects together with the leukocyte and platelet levels in the graft determine the mediator profile of the stem cell grafts. Graft infusion also alters the systemic mediator profile of the recipients, but further studies are required to clarify whether such graft-induced alterations have a prognostic impact.

Keywords: allogeneic stem cell transplantation; apheresis; chemokine; granulocyte colony-stimulating factor; hematopoietic stem cell mobilization; interleukin; peripheral blood stem cell grafts; plasma profile; protease; soluble adhesion molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allografts / drug effects
  • Blood Component Removal*
  • Blood Platelets / cytology
  • Cytokines / blood
  • Disease-Free Survival
  • Female
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunologic Factors / metabolism*
  • Leukocytes / cytology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Solubility
  • Tissue Donors*

Substances

  • Cytokines
  • Immunologic Factors
  • Granulocyte Colony-Stimulating Factor