In vitro quantitation of lethal and physiologic effects of total body irradiation on stromal and hematopoietic stem cells in continuous bone marrow cultures from Rf mice
- Havard Medical School, Boston, MA
The effects of in vivo total body irradiation (TBI) and interval from TBI to explant of marrow on: stromal cell proliferation in vitro; stromal cell support of hematopoiesis in continuous bone marrow culture; and generation of WEHI-3 growth factor (GF)-dependent lines of hematopoietic progenitor cells were evaluated. Explant of marrow at 2, 4, 5, or 6 months after single fraction TBI (300-800 rad) was associated with decreased longevity of hemopoiesis and a decrease in the proliferative capacity of fibroblastic adherent-stromal colony forming cells (CFUf) as measured by colony size at 14 days and number of colonies per 10/sup 6/ cells plated. In contrast, explant of marrow 8 to 24 months after TBI produced cultures with longevity that was indistinguishable from age-matched control cultures (19-24 weeks). Marrow from irradiated first and second generation recipients of serially transferred marrow demonstrated a similar 7-month in vivo recovery period; however, the plateau maximum duration of hemopoiesis did not return to control levels. Purified stromal cell cultures were prepared by corticosteroid-deprivation of explanted marrow for 28 days and were then engrafted in vitro with marrow from C57BL/6J or RfM/UN mice that had been irradiated 1 month previously. Hemopoiesis in these cultures was restored, and they produced GM-CFUc and granulocytes for 15-24 weeks. Thus, healthy stroma supported growth of recently irradiated hemopoietic cells in vitro. Indirect effects of x-irradiation on hemopoietic stem cells through damage and repair in the stromal cell compartment can be effectively studied with the present bone marrow culture system. (JMT)
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 7066055
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 8:7
- Country of Publication:
- United States
- Language:
- English
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MICE
WHOLE-BODY IRRADIATION
STEM CELLS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL REPAIR
BLOOD FORMATION
BONE MARROW
CELL PROLIFERATION
DOSE-RESPONSE RELATIONSHIPS
IN VITRO
X RADIATION
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BODY
ELECTROMAGNETIC RADIATION
EXTERNAL IRRADIATION
HEMATOPOIETIC SYSTEM
IONIZING RADIATIONS
IRRADIATION
MAMMALS
ORGANS
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RADIATIONS
RECOVERY
REPAIR
RODENTS
SOMATIC CELLS
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560152* - Radiation Effects on Animals- Animals
560121 - Radiation Effects on Cells- External Source- (-1987)