Haemopoietic stem cell subpopulations in mouse and man: discrimination by differential adherence and marrow repopulating ability.

Based on the properties of differential cell adherence, we have devised two assays for early progenitor cells in human bone marrow. One progenitor cell population binds to plastic and to pre-formed bone marrow derived stromal layers (P+S+) and gives rise to non-adherent granulocyte-macrophage colony-forming cells (GM-CFC); the other binds to stromal layers but not to plastic (P-S+); both are separable from GM-CFC which are P-S-. We have evaluated the relevance of differential binding properties to marrow repopulation in a murine model. Murine stem cells (spleen colony-forming cells--CFU-S) can be separated into P+S+, P-S+ and P-S- subpopulations by differential adhesion, thus paralleling the progenitor cell subpopulations in human marrow. Post irradiation (850 cGy X-rays) studies have shown that the P+S+ cells are essential for survival and recovery of marrow, spleen and blood cell populations. Also, in a model for purging autografts, we have demonstrated that the leukaemic cells can be separated from P+S+ repopulating cells by exploiting their different binding properties.

Adhesive properties distinguish sub-populations of haemopoietic stem cells with different spleen colony-forming and marrow repopulating capacities.

The adhesive properties of clonogenic haemopoietic progenitor cells have been assessed by allowing them to bind to cultured marrow-derived stromal layers, stromal cell lines or bare plastic surfaces. We have compared the adhesive characteristics of murine marrow repopulating cells, spleen colony-forming cells (CFU-S) and granulocyte-macrophage colony-forming cells (GM-CFC) and of human blast colony-forming cells (Bl-CFC). The data indicate, first, that murine marrow repopulating cells bind to plastic and to stromal layers. Second, the CFU-S compartment contains three sub-populations: (a) CFU-S that bind to plastic and to stroma; (b) CFU-S that bind to stroma but not to plastic; (c) CFU-S that do not bind to stroma or plastic. Third, that more mature GM-CFC are not adhesive in these tests; and fourth, that recognitive events between stem cells and marrow stroma can operate across species barriers. Adhesion to both marrow-derived stroma and plastic appears to be a characteristic of haemopoietic stem cells that is lost or modulated as cells differentiate.