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Primitive long-term culture initiating cells (LTC-ICs) in granulocyte
colony-stimulating factor mobilized peripheral blood progenitor cells have
similar potential for ex vivo expansion as primitive LTC-ICs in steady
state bone marrow
F Prosper, K Vanoverbeke, D Stroncek and CM Verfaillie
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
We have recently shown that more than 90% of long-term culture initiating
cells (LTC-IC) mobilized in the peripheral blood (PB) of normal individuals
express HLA-DR and CD38 antigens and can sustain hematopoiesis for only 5
weeks. However, 10% of LTC-IC in mobilized PB are CD34+ HLA-DR- and CD34+
CD38- and can sustain hematopoiesis for at least 8 weeks. We now examine
the ex vivo expansion potential of CD34+ HLA-DR+ cells (rich in mature
LTC-IC) and CD34+ HLA-DR- cells (rich in primitive LTC-IC) in granulocyte
colony-stimulating factor (G-CSF) mobilized PB progenitor cells (PBPC).
Cells were cultured in contact with M2-10B4 cells (contact) or in
transwells above M2-10B4 (noncontact) without and with interleukin-3 (IL-3)
and macrophage inflammatory protein (MIP-1alpha) for 2 and 5 weeks. Progeny
were evaluated for the presence of colony-forming cells (CFC) and LTC-IC.
When CD34+ HLA-DR+ PB cells were cultured in contact cultures without
cytokines, a threefold expansion of CFC was seen at 2 weeks, but an 80%
decrease in CFC was seen at week 5. Further, the recovery of LTC-IC at week
2 was only 17% and 1% at week 5. This confirms our previous observation
that although CD34+ HLA-DR+ mobilized PB cells can initiate long-term
cultures, they are relatively mature and cannot sustain long- term
hematopoiesis. In contrast, when CD34+ HLA-DR- mobilized PB cells were
cultured in contact cultures without cytokines, CFC expansion persisted
until week 5 and 49% and 11% of LTC-IC were recovered at week 2 and 5,
respectively. As we have shown for steady state bone marrow (BM)
progenitors, recovery of LTC-IC was threefold higher when CD34+ HLA-DR-
PBPC were cultured in noncontact rather than contact cultures, and improved
further when IL-3 and MIP-1alpha were added to noncontact cultures (96 +/-
2% maintained at week 5). We conclude that although G- CSF mobilizes a
large population of "mature" CD34+ HLA-DR+ LTC-IC with a limited
proliferative capacity, primitive CD34+ HLA-DR- LTC-IC present in mobilized
PB have similar characteristics as LTC-IC from steady state BM: (1) they
can be maintained in noncontact cultures containing IL-3 and MIP-1alpha for
at least 5 weeks; (2) they are subject to the same proliferation inhibitory
influences of contact with stroma. Since the absolute number of primitive
LTC-IC (week 8 LTC-IC) per mL of G-CSF mobilized PB is similar to that per
mL of steady state BM, these studies further confirm that G-CSF mobilized
PBPC may have similar long-term repopulating abilities as steady state BM.
Volume 89,
Issue 11,
pp. 3991-3997,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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