Objective: 

Stem cells that can self-renew, proliferate and differentiate are indispensable component for regeneration of hematopoietic system. In chemotherapy applications, malign and normal cells are together damaged. Corticosteroids, essential drug for all chemotherapy protocols, efficiently induce apoptosis not only in malign cells also in normal hematopoietic cells. In several studies, it has been showed that cytokines can supress apoptosis induced by chemotherapy. In this study, for the first time we investigated apoptotic effects of corticosteroids on pure CD34+ hematopoietic stem cell population collected from human peripheral blood buffy coats by using immunomagnetic positive selection method and protective effects of cytokines.

Methods: 

Control groups were incubated with serum-free medium (SFC) and induced with cytokine coctail including interleukin3, thrombopoietin, stem cell factor and flt3/flk2ligand (CC). Test groups were dexamethasone group (D), prednisolone group (P) and groups induced with cytokines before drug application (CD, CP).

To determine apoptotic mechanisms, immunohistochemical staining was carried out with monoclonal fas, caspase3, cytochromeC, bax and bcl-2 antibodies, degree of peroxidase reactions were quantified using H-score. For statistical analysis paired t-test and one sample t-test were used.

Results: 

As a result, both dexamethasone and prednisolon induced apoptosis. Compared with control groups, corticosteroids application caused a significant increase for all apoptotic markers (p<0.05), and a significant decrease for anti-apoptotic bcl-2 (p<0.05). Also, cytokines caused a significant decrease for all apoptotic markers (p<0.05) and a significant increase for bcl-2 (p<0.05).

Conclusions: 

So that, corticosteroids induced apoptosis in human CD34+ hematopoietic stem cells and cytokines decreased apoptotic effects of these agents and prevented apoptosis.