Mutually reinforcing studies reported by Taniguchi et al. 1 in this issue of Nature Medicine and elsewhere by Murase et al. 2 have provided important insights into transplantation immunology. Both investigations show that pluripotent hematolymphopoietic stem cells reside in the liver of mature rodents, and by inference in other organs. The crucial evidence supporting this phenomenon is provided by the reconstitution of supralethally irradiated mice (9.5 Gy) with stem cells purified from adult mouse livers1 and the rescue of irradiated rats by the direct expedient of liver transplantation2. With either approach, all hematolymphopoietic lineages are restored in the recipients.

Two historical contributions preceding these results are noteworthy, both also involving supralethal irradiation of recipients before transplantation. In the first report, Hays et al. 3 describe multilineage reconstitution in mice with cultured syngeneic hepatic nonparenchymal cells (NPCs) obtained from adult mouse liver.(Reconstitution was most marked when NPCs were cultured from regenerating liver.) More recently, Decker et al. emphasized the equivalence of reconstitution in recipients transplanted with cultured syngeneic liver NPCs versus bone marrow cells. Using sophisticated contemporary technology, Taniguchi et al. have greatly extended these observations, showing that the frequency of pluripotent stem cells in the mouse liver is at least half that in bone marrow and about five times that in peripheral blood. As few as 500 of these sorted cells isolated from the NPCs of adult mouse liver allow full reconstitution of irradiated recipients.