The Effect of Granulocyte Colony-Stimulating Factor on Immune-Modulatory Cytokines in the Bone Marrow Microenvironment and Mesenchymal Stem Cells of Healthy Donors.
Granulocyte colony stimulating factor (G-CSF) is sometimes administered to donors before bone marrow (BM) harvest. G-CSF-primed (G-BM) and unprimed BM (U-BM)-derived mesenchymal stem cells (MSC) were obtained from 16 healthy donors and were expanded in vitro. Their proliferative characteristics, morphology, and differentiation capacity were examined. Supernatants of the second passage of MSCs were evaluated for transforming growth factor β1, hepatocyte growth factor, and prostaglandin E2 (PGE2) levels and compared with controls. The analyses of cytokines in the G-BM- and U-BM-derived MSCs supernatants revealed that PGE2 levels were significantly lower in the G-CSF-primed samples. These cytokines were also measured in BM plasma. The level of hepatocyte growth factor in G-BM plasma was significantly increased. The current study is the first to show the effects of G-CSF on the BM microenvironment of healthy human donors. The preliminary data suggest that G-BM- and U-BM-derived MSCs have similar morphologic/phenotypic properties and differentiation capacity but differ in their secretory capacity. Significant changes in cytokine levels of BM plasma in G-CSF-primed donors were also demonstrated. These findings suggest that BM MSCs and changes in the BM microenvironment may contribute to the effects of G-CSF on inflammation and immunomodulation.
Department of Pediatric Hematology, Ankara Children's Hematology Oncology Education and Research Hospital, Ankara, Turkey. Electronic address: ikbalok@yahoo.com.
Ikbal
I
Ok Bozkaya
Department of Pediatric Hematology, Ankara Children's Hematology Oncology Education and Research Hospital, Ankara, Turkey.
Fatih
F
Azik
Department of Pediatric Hematology, Hacettepe University, Ankara, Turkey.
Betul
B
Tavil
Stem Cell Research Laboratory, Department of Pediatric Hematology Oncology, Ankara Children's Hematology Oncology Education and Research Hospital, Ankara, Turkey.
Yasin
Y
Koksal
Stem Cell Research Laboratory, Department of Pediatric Hematology Oncology, Ankara Children's Hematology Oncology Education and Research Hospital, Ankara, Turkey.
Meltem
M
Ozguner
Department of Pediatric Hematology, Ankara Children's Hematology Oncology Education and Research Hospital, Ankara, Turkey.
Bahattin
B
Tunc
Department of Pediatric Hematology, Hacettepe University, Ankara, Turkey; Center for Stem Cell Research and Development, Hacettepe University, Ankara, Turkey.
Duygu
D
Uckan Cetinkaya
D000293:Adolescent; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D061251:Primary Cell Culture; D014019:Tissue Donors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D017077:Culture Media, Conditioned; C066855:HGF protein, human; D053773:Transforming Growth Factor beta1; D016179:Granulocyte Colony-Stimulating Factor; D017228:Hepatocyte Growth Factor; D015232:Dinoprostone
Bone marrow; Granulocyte colony–stimulating factor; Hepatocyte growth factor (HGF); Mesenchymal stem cell; Prostaglandin E2 (PGE2); Transforming growth factor β1 (TGF-β1)