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.
Gordon
M Y
MY
Leukaemia Research Fund Centre for Adult Leukaemia, Royal Postgraduate Medical School, London.
Lewis
J L
JL
Scott
M A
MA
Roberts
I A
IA
Goldman
J M
JM
D000328:Adult; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans