Probability of progenitor renewal (PPR) and production of clonogenic progeny (CFU-GM) by primitive adherent progenitor cells in adult human bone marrow and umbilical cord blood

Summary. Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (PΔ cells) that can be detected by measurement of their granulocyte-macrophage colony-forming cell (CFU-GM) progeny. Limiting dilution analysis and Poisson statistics are necessary for determining the frequency of PΔ cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual PΔ progenitors to produce CFU-GM. Here we report that the frequencies of PΔ progenitors in cord blood and adult marrow are similar (5.6 and 7.8/10⁵ mononuclear cells respectively) and individual cord blood PΔ progenitors produce fewer CFU-GM than adult PΔ progenitors. To test the possibility that the lower production of differentiated progeny by cord blood cells was the result of a higher rate of self-renewal, we devised a two-stage limiting dilution assay relying on the relative production of CFU-GM after two consecutive weeks of incubation. The probability of progenitor renewal (PPR) was derived from the number of wells (progenitors) that produced CFU-GM on both occasions compared with the number that produced CFU-GM on the first occasion only. The total number of CFU-GM produced on the second occasion compared with the number produced on the first occasion provided an index of the overall change in the size of the PΔ cell population. The data indicate that PΔ cells in cord blood have a higher PPR (0.59) than those in adult marrow (036). Also, the relative numbers of CFU-GM produced in the second and first weeks were greater for cord blood (1.2) than for adult marrow (0.36). Therefore PΔ cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than PΔ cells in adult marrow.