In vivo expansion of hemopoietic stem cells

Under conditions of steady‐state hemopoiesis, a small fraction of immature hemopoietic cells, including stem cells, circulates in peripheral blood (PB). In rhesus monkeys, a median number of 1.2 × 10 7 /l CD34 + cells was observed as opposed to a median number of 1.5 × 10 9 /l in aspirated bone marrow (BM). The concentration of circulating CD34 + cells is therefore approximately two logs less than that in BM. Since a 4‐kg rhesus monkey has an estimated number of 3 × 10 10 BM cells and approximately 300 ml of blood, the fraction of CD34 + cells that circulates can be estimated at approximately 0.4% of the total pool of CD34 + cells. During hemopoietic reconstitution following a cytotoxic insult such as results from a midlethal dose of TBI, PB CD34 + cell numbers appeared to be correlated to those of BM, suggesting that PB CD34 + cells may reflect reconstitution of BM CD34 + cells. Reconstitution of BM immature cells can be accelerated by treatment with pharmacological doses of growth factors, resulting in largely expanded immature cell populations within a few weeks after TBI. Growth factors observed to exert such an effect included, notably, thrombopoietin. Such an acceleration can be monitored by daily assessment of circulating CD34 + cells. Expansion of immature circulating cells indicates expansion of similar cells in the bone marrow rather than growth factor‐induced selective mobilization of immature cells.