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Radiation effects on haematopoietic stem cells in vitro: possible role of stromal niches in the stem cell hierarchy.

An increasing variety and number of therapeutic protocols involve the irradiation of large pro-portions of the sites of haematopoiesis in some patients. A long term consequence of such exposure is the occasional induction of malignancies. These are often but not exclusively second malignancies which are frequently of haematopoietic origin (Penn, 1981). The relative contribution of radiation effects on haematopoietic stem cells (HSC) or micro- environmental stromal cells (MSC) to these long term post-exposure observations remains uncertain (Testa et al., 1985). This is partly because of the increasing realization that the behaviour of stem cells and stromal cells is not independent (Spooncer et al., 1985). Increasingly, it is evident that stromal cells are involved in the regulation of haematopoiesis, particularly via the more primitive mem- bers of the HSC hierarchy (Sharp et al., 1985). The ability to maintain HSC in long term culture (LMTC) when in contact with a requisite stroma (Dexter et al., 1977) appeared to offer the oppor- tunity to dissect the differential effects of radiation. on HSC versus MSC. However, this methodology leads to some peculiar radiobiological results which potentially occur because of the effects of HSC- MSC interactions. We briefly describe these effects together with some experiments which attempt to elucidate the nature of HSC-MSC interactions.