Hemopoiesis during thiamphenicol treatment. II. A theoretical analysis shows consistency of new data with a previously hypothesized model of stem cell regulation.
In a recent theoretical model of stem cell regulation, specific quantitative assumptions were made about an in vivo feedback process from erythroid and granuloid precursor cell stages to the spleen colony-forming units (CFU-S), erythroid burst-forming units (BFU-E), and granulocyte-macrophage colony-forming units (CFU-GM). Utilizing specific effects of the antibiotic thiamphenicol (TAP), new experiments have been performed to challenge this model. Here these data are treated in an analysis that implies three steps. First, model assumptions about TAP toxicity are justified. The toxic TAP effects on erythroid and granuloid precursors are quantified as a continuous reduction of the normal amplification coefficient for CFU-E (down to 1/250), proerythroblasts, basophilic erythroblasts, and proliferating granuloid precursors (down to 1/4). Second, the original model predictions for the behavior of CFU-S, CFU-GM, and BFU-E are compared with the corresponding data. Third, discrepancies are discussed and it is demonstrated that adjustment of one single parameter resolves most of them. Thus one can quantitatively explain the experimental results for CFU-S, BFU-E, and CFU-GM by an activation of the regulatory process postulated: the decline in erythroid (and granuloid) cell numbers enhances the cycling of CFU-S while their self-renewal probability is reduced; consequently CFU-S numbers decline; as more cells differentiate towards BFU-E and CFU-GM per unit time the cell numbers of these cell stages increase. Thus the new data on stem cell behavior during TAP treatment support the hypothesis of a feedback from erythroid and granuloid precursors to the stem cells.
Loeffler
M
M
Medical Clinic I, University of Cologne, Federal Republic of Germany.
Bungart
B
B
Goris
H
H
Schmitz
S
S
Nijhof
W
W
D000818:Animals; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000187:drug effects; D005246:Feedback; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D008962:Models, Theoretical; D013154:Spleen / Q000166:cytology; D013839:Thiamphenicol / Q000494:pharmacology*
D013839:Thiamphenicol