SUMMARY: Two bone marrow cell populations, separately identifiable by means of chromosome markers, were serially transferred at 8-10 week intervals through lethally irradiated syngeneic recipients. This system allowed a precise comparison of populations derived from young and old donors; no consistent differences were observed. Both donor populations ceased to replicate after 4-5 transfers. Although more than 103 spleen colony-forming units were transferred, the number of clones proliferating in the bone marrow fell sharply between the second and third transfer-generations. Regenerating host cells accounted for an increasing proportion of the mitoses scored in the third and subsequent transfer generations. It is concluded that many of the stem cells of bone marrow subjected to two or more transfers have decreased powers of self renewal. The results suggest that stem cells of adult mouse bone marrow are capable of undergoing, at most, between 80 and 200 mitoses. This limitation is very possibly innate, but the possibility that it is an artifact of the serial transfer system cannot be entirely ruled out.
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