Rescue from lethal irradiation correlates with transplantation of 10-20 CFU-S-day 12

Area of Science:

• Hematology
• Stem Cell Biology
• Radiation Biology

Background:

• Bone marrow ablation by irradiation leads to two repopulation phases: temporary initial and permanent long-term repopulating cells (LTRC).
• The identity and role of cells responsible for initial, temporary repopulation remain unclear.
• Long-term repopulating cells (LTRC) are known to restore the entire lympho-hematopoietic system.

Purpose of the Study:

• To identify the cell type and quantify the number of cells required for initial survival following lethal irradiation.
• To investigate the role of colony-forming units in spleen (CFU-S) in the early stages of bone marrow reconstitution.

Main Methods:

• Transplantation of bone marrow subpopulations enriched for LTRC and varying in progenitor content.
• Cell discrimination using antibody reactivity, Hoechst 33342 and rhodamine 123 fluorescence, and light scattering.
• Assessment of minimum rescue inocula for lethally irradiated recipients.

Main Results:

• Initial survival (radioprotection) correlated with the presence of 1-2 colony-forming units in spleen at day 12 (CFU-S-12) per rescue inoculum.
• Studies suggest that 10-20 CFU-S-12 are necessary for effective radioprotection.
• A single CFU-S-12 is insufficient to provide adequate peripheral blood cells for recovery by days 12-14.
• 5-fluorouracil-treated marrow subpopulations showed reduced initial repopulation capacity at low cell doses.

Conclusions:

• Initial bone marrow repopulation and radioprotection are mediated by multiple CFU-S-12, not single cells.
• The number of CFU-S-12 is a critical determinant for early hematopoietic recovery after lethal irradiation.
• Cell dose and pre-treatment (e.g., 5-fluorouracil) impact the efficacy of bone marrow subpopulations in initial repopulation.