Virtual serial transplantation experiment in mice. (A) The numbers of HSCs 12 weeks after an initial transplantation and after 3 retransplantations. Optimized values for λ (once per 2.5 weeks), α (once per 20 weeks), ν (once per 3.4 weeks), and μ (6.9 weeks) were used,³  and are preset in the simulation tool. In these simulations of serial transplantations, mice receive 4% of the number of HSCs present 12 weeks after the previous transplantation. Histograms correspond to 1000 independent simulations of this process: as shown, by the third transplantation (recipient 3), ∼70% of the 1000 virtual mice fail to reconstitute. By the final sequential transplantation, almost all virtual mice have a depleted HSC reserve (ie, zero compartment 1 cells). (B) Similar histograms of the numbers of HSCs in the final recipients, and show the effects of varying the percentage of marrow cells transplanted and varying length of time between the sequential transplantation. As expected, transplanting higher percentages of marrow cells or waiting longer between transplantations ameliorates the quantity of HSC dilution; the rightmost histogram shows that only about one-third of the simulated mice will die of a lack of HSCs when doubling the parameters of the experiment in panel A.