Models relevant to radiation effects on stem cell pools

The available evidence clearly indicates the existence of a pluripotential primitive stem cell population (CFU). In the normal animal a large proportion of this population will 'sit' in the G0 state. At any time a small proportion of these cells will differentiate into one or more 'precursor' populations. One such precursor population is the erythropoietin responsive cell (ERC) and it is important to realize that this population has a significant number of mitoses in it, i.e. it is capable of considerable, although not indefinite proliferation. This is indicated by the colony growth during which, from a single colony former, large numbers of differentiated cells can be formed, in excess of several millions, at a time when the CFU numbers in the colony are still very small. To understand then the effects of radiation on this complex series of populations the following will have to be borne in mind. The ultimate stem cells are, at least in the small rodent, the CFU. It is their quantity that is essential for regeneration. However, the normal rate of differentiation of CFU in the small rodent is very low. This is because this rate of differentiation gives rise to a possibly committed precursor cell population such as the ERC, or possibly the agar forming 'GRC', the precursor populations with considerable proliferative potential in them. Therefore, after relatively small doses of radiation, or even during a regime of continuous irradiation, the proliferative potential of these transit precursor populations will be able to cope with near normal haemopoiesis at a time when the number of colony formers is gradually depleted. It is also significant that the rate of seeding of the primitive colony former is not related to its numbers and, therefore, under conditions of partial irradiation, at least in the small rodent, greatly increased relative migration and to some extent increased absolute migration of the CFU is possible, with consequent enhancement of the regeneration of haemopoiesis. There is no information available to indicate what regulates the differentiation of the primitive CFU into the ERC or other similar precursor populations. There is also no clear or unequivocal evidence which could indicate whether the ERC and the potential GRC are different or related to each other. There is no information available on a committed precursor population for the thrombocytic series of cells. There is, however, evidence in the small rodent that the potential focus-forming cells detected by immunological methods may represent a precursor population, specific for future antibody-producing cells. The mechanisms involved in the 'second step' differentiation, e.g. that of the ERC into the erythron, are beginning to be understood and it is clear that humoral factors, e.g. erythropoietin, are involved. There is also increasing evidence for the existence of a humoral thrombopoietic factor, although no clear evidence is yet available regarding the existence of a 'granulopoietin'. The outstanding problem at the moment is to understand the mechanisms regulating the differentiation of the CFU into the precursor populations and the nature of the control of the population size of the CFU population itself. Understanding and eventual manipulation of these two phenomena would greatly enhance our capacity in modifying radiation damage to haemopoietic tissues