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

Human haemopoietic tissues contain primitive plastic-adherent progenitor cells (P Delta 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 P Delta cells because each of them produces several CFU-GM. Limiting dilution also permits measurement of the abilities of individual P Delta progenitors to produce CFU-GM. Here we report that the frequencies of P Delta progenitors in cord blood and adult marrow are similar (5 . 6 and 7 . 8/10(5) mononuclear cells respectively) and individual cord blood P Delta progenitors produce fewer CFU-GM than adult P Delta 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 P Delta cell population. The data indicate that P Delta cells in cord blood have a higher PPR (0 . 59) than those in adult marrow (0 . 36). 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 P Delta cells in cord blood have a greater capacity for self-maintenance and possibly for expansion than P Delta cells in adult marrow.