Effects of recombinant cytokines on colony formation by irradiated human cord blood CD34+ hematopoietic progenitor cells.
The role of recombinant hematopoietic growth factors in radiation repair has become a subject of increasing interest in both clinical and basic radiobiology. Combinations of cytokines such as hepatocyte growth factor, interleukin (IL)-3, IL-11, kit ligand, GM-CSF and erythropoietin were used to study the in vitro radiation dose response of human cord blood CD34+ hematopoietic progenitor cells using clonogenic survival assays. CD34+ cells were isolated by immunomagnetic selection and irradiated at 8 cGy/min. Irradiated cells were plated in methylcellulose with or without added cytokines, and hematopoietic colonies including CFU-GM, BFU-E and CFU-GEMM were scored on day 14. The radiation response characteristics of BFU-E and CFU-GEMM were similar for all culture conditions tested. The D0 values for BFU-E ranged between 1.29 and 2.40 Gy and n between 1.0 and 1.4. The D0 values for CFU-GEMM ranged from 86 cGy to 2.02 Gy and n between 1.0 and 1.5. The D0 for CFU-GM grown without added factors was 1.03 Gy. With single cytokine stimulation (IL-3, IL-11 or varying concentrations of HGF), D0 values ranged from 1.11 to 1.44 Gy. With the combination of IL-3, GM-CSF, kit ligand and HGF, D0 values were not significantly altered and ranged between 1.61 and 2.60 Gy. In contrast, the combination of IL-11 and HGF produced an increase in the shoulder of the radiation survival curve (n = 3.35). No increase in the shoulder was detected for any of the other conditions tested (n = 1.0-1.7). Thus the combination of HGF and IL-11 increased the radiation survival of hematopoietic progenitor cells forming CFU-GM. Understanding the mechanism by which combinations of early-acting growth factors support postirradiation recovery of primitive clonogenic hematopoietic cells may be relevant to the design of clinical protocols for improving hematopoietic recovery after total-body irradiation.
Goff
J P
JP
Department of Radiation Oncology, University of Pittsburgh Cancer Institute Pennsylvania, USA.
Shields
D S
DS
Boggs
S S
SS
Greenberger
J S
JS
D015703:Antigens, CD; D018952:Antigens, CD34; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D002588:Cesium Radioisotopes; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004921:Erythropoietin / Q000494:pharmacology; D005312:Fetal Blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013997:Time Factors
D015703:Antigens, CD; D018952:Antigens, CD34; D002588:Cesium Radioisotopes; D016207:Cytokines; D017370:Interleukin-11; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D017228:Hepatocyte Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor