Stem cell transplantation in the normal nonmyeloablated host: relationship between cell dose, schedule, and...

In previous studies we have shown high rates of stable engraftment when 40 million male BALB/c cells were infused intravenously daily for 5 days (a total of 200 million cells) to normal nonmyeloablated female hosts. The present studies evaluate engraftment of male BALB/c bone marrow cells in female host marrow, spleen, and thymus 20-25 weeks after transplantation using varying cell dosages within a 5-day schedule. Engraftment in recipient mice was assessed by detection of male specific sequence in recipient DNA from each organ. When 40 million cells were given per daily injection for 1, 2, 3, 4, or 5 days, engraftment percentages in host marrow were 11 +/- 0.83, 20 +/- 2.0, 23 +/- 2.5, 32 +/- 6.3, and 39% +/- 5.7 (+/- standard error of mean), respectively, yielding engraftment percentages per million cells infused of 0.28, 0.25, 0.19, 0.20, and 0.20%, respectively. When levels of 2.5, 5, 10, 20, or 40 million cells were injected 5 times over a 5-day schedule into normal BALB/c female hosts, progressively increasing levels of engraftment from 3 +/- 0.6 to 39% +/- 5.7 were seen in host marrow. Highest levels of engraftment per million cells injected were obtained on days 1 and 2 of a 5-day schedule and with a level of 10 million cells given daily over 5 days. Engraftment profiles varied with spleen and thymus and percent engraftment was generally lower than for marrow. The present work indicates that regardless of cell level infused or number of infusions, rates of engraftment observed in marrow approached or exceeded the highest rates of engraftment estimated by theoretical calculations based on replacing host cells ("replacement model") or adding to host cells ("incremental model"). Engraftment in spleen and thymus was lower, but also at times approached or exceeded theoretical maxima. These data show extraordinary levels of engraftment in normal hosts, suggesting that rates in this competitive model are superior to those seen in irradiated hosts; alternatively, there may be selective repression of host stem cell proliferation and differentiation.