PHENOTYPIC DIFFERENCES AMONG STEM-CELLS ( SC) FROM DIFFERENT CELL SOURCES USED FOR TRANSPLANTATION

Transplantations to restore the hematopoietic system were originally p erformed with cells from the bone marrow (BM) (20) which was considere d the only cell source comprising repopulating progenitor cells. The d iscovery that chemotherapy induced the mobilization of CD34(+) cells i nto the peripheral blood (PB) (14) gave rise to the successful autolog ous transplantation of PBSC (1, 13). Also cord blood (CB) was found to contain considerable numbers of ''stem cells'', and to date at least 42 allogeneic transplantations have been performed with this cell sour ce (22, J. Wagner, personal communication). Further investigations led to the successful autologous transplantation of positively selected C D34(+) cells from BM and PB (18), and the latest results indicate that it is promising to transplant purified CD34(+) cells obtained from cy tokine-stimulated donors (4, 10, 15-16). Despite such achievements it remains unclear how many ''stem cells'' are required per kg of the rec ipient and how they are phenotypically characterized. In this communic ation we give examples of typical differences observed by flow cytomet ry and clono-genic assay between the CD34(+) cells contained in the di fferent cell sources. They may explain why it is not sufficient only t o analyze the CD34(+) cell populations which may represent progenitors of different lineages as well as of various states of differentiation . CB CD34(+) cells are early myeloid progenitor cells with the highest incidence of CFU-mix among the three cell sources. They have a high p roliferative potential in vitro. They hardly coexpress B cell antigens and they are partially negative for CD38. Their majority is negative for CD45RA (8). Among the three cell sources, they have the greatest p roportion of CD34(+)/CD11a(-) cells. The fact that CD34(+) cells coexp ress CD33 and HLA-DR indicates that the latter antigens may not only r epresent differentiation markers (7). The prolonged period of 25 days post transplantation to reach > 500 neutrophils/mu l (22) may be due t o the early differential state of the progenitors and/or to low CD34 n umbers transplanted per kg. In contrast to CB, the majority of BM CD34 (+) cells represent relatively committed progenitors as indicated in v itro by a lower cloning efficiency and by high numbers of CFU-G and CF U-M in favour of BFU-E and mainly CFU-mix. Flow cytometry revealed abo ut 80%-90% of the CD34(+) cells to coexpress CD45RA. A variable propor tion (0% to >70%) of the BM CD34(+) MNC may represent B cell progenito rs which are positive for CD45RA and which would not support myeloid c ell recovery after transplantation. Chemotherapeutic treatment as well as growth factor stimulation cause the mobilization of CD34(+) cells from the BM to the PB. It is noteworthy that B cell progenitors are no t, and committed progenitors are hardly mobilized. The PBSC usually re present relatively early myeloid cells the majority of which is negati ve or dim for CD45RA although they are more differentiated than the CB CD34(+) cells. The observation that CB as well as steady state and cy tokine-mobilized PB progenitor cells are never in cell cycling phase ( S/G(2)M) which is in sharp contrast to BM CD34(+) MNC, indicates the r ole of the BM microenvironment for the progenitor cell proliferation ( Leitner et al., submitted).