Blood stem cells are extracted most often from the peripheral blood of donors and occasionally from their bone marrow. Because there are significantly fewer stem cells in peripheral blood than in bone marrow, doctors prepare peripheral blood donors by injecting them with a series of growth factors to move blood stem cells from their marrow into their bloodstream. This increases the blood stem cells concentration 10- to 100-fold in the blood.

If stem cells are harvested from bone marrow, the donor is placed under general anesthesia. In a procedure that takes about an hour, marrow is removed through a large needle inserted into the donor's pelvic bones, and it is processed to remove blood and bone fragments. After the collection is completed, the donor may be given a transfusion of his or her own red blood cells from units of blood that were self-donated a week earlier.