Effects of Recombinant Cytokines on Colony Formation by Irradiated Human Cord Blood CD34+ Hematopoietic Progenitor Cells

• Published in: Radiation research 1997-01, Vol.147 (1), p.61-69
• Main Authors: Goff, Julie P., Shields, Donna S., Boggs, Sallie S., Greenberger, Joel S.
• Format: Article
• Language: English
• Subjects: Antigens, CD; Antigens, CD34; Biological and medical sciences; Blood; Cell growth; Cell physiology; Cell Survival - drug effects; Cell Survival - radiation effects; Cells, Cultured; Cesium Radioisotopes; Colony-Forming Units Assay; Cord blood; Cytokines; Cytokines - pharmacology; Dose-Response Relationship, Radiation; Drug Interactions; Effects of physical and chemical agents; Epics; Erythropoietin - pharmacology; Fetal Blood; Fundamental and applied biological sciences. Psychology; Granulocyte macrophage progenitor cells; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - radiation effects; Hepatocyte Growth Factor - pharmacology; Hepatocytes; Humans; Interleukin-11 - pharmacology; Interleukin-3 - pharmacology; Irradiation; Kinetics; Molecular and cellular biology; Progenitor cells; Recombinant Proteins - pharmacology; Stem cell factor; Stem Cell Factor - pharmacology; Time Factors
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3579444

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 n̄ between 1.0 and 1.4. The D0 values for CFU-GEMM ranged from 86 cGy to 2.02 Gy and n̄ 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 (n̄ = 3.35). No increase in the shoulder was detected for any of the other conditions tested (n̄ = 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.