The Rate of Marrow Recovery and Extent of Donor Engraftment Following Transplantation of Ex Vivo–Expanded Bone Marrow Cells Are Independently Influenced by the Cytokines Used for Expansion

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Abstract
Successful stem cell transplantation depends on cell dose, and this is particularly true for placental/ cord blood transplantation in which it has been clearly shown that both the success of engraftment as well as the speed of white cell and platelet recovery are dependent on the nucleated cell dose in the graft. Thus, if stem cell numbers could be increased, the speed as well as the likelihood of engraftment might be improved. We studied the effect of two different cytokine combinations— kit ligand (KL), interleukin-3 (IL-3), and Flt-3 ligand supplemented with thrombopoietin and IL- 11 (combination 1) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and G-CSF (combination 2)—for their ability to affect speed and extent of engraftment using limited numbers (5 × 104) of murine bone marrow (BM) light-density (LD) cells or their progeny expanded ex vivo in the presence one or the other cytokine combination for 6 days. With combination 1, we found that speed of platelet recovery was enhanced, but at the expense of white blood cell (WBC) recovery and percent donor engraftment. Furthermore, the cytokine combination that best maintained donor engraftment, combination 2, did so at the expense of platelet recovery. In no case was percent donor engraftment improved over 5 × 104 unmanipulated LD BM cells. These results are consistent with the interpretation that immediate recovery of blood cells of different lineages and longterm donor engraftment are separate functions that can be influenced by the choice of cytokines used during the ex vivo expansion process.

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