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Maintenance of transplantation potential in ex vivo expanded CD34(+)-
selected human peripheral blood progenitor cells
R Henschler, W Brugger, T Luft, T Frey, R Mertelsmann and L Kanz
Department of Hematology/Oncology, Albert Ludwigs University Freiburg
Medical Center, Germany.
CD34(+)-selected hematopoietic progenitor cells are being increasingly used
for autotransplantation, and recent evidence indicates that these cells can
be expanded ex vivo. Of 15 patients with solid tumors undergoing a phase
I/II clinical trial using CD34(+)-selected peripheral blood progenitor
cells (PBPCs) after high-dose chemotherapy, we analyzed the frequency of
long-term culture-initiating cells (LTCIC) as a measure of transplantation
potential before and after ex vivo expansion of CD34+ cells. PBPCs were
mobilized by combination chemotherapy and granulocyte colony-stimulating
factor (G-CSF). The original unseparated leukapheresis preparations, the
CD34(+)-enriched transplants, as well as nonabsorbed fractions eluting from
the CD34 immunoaffinity columns (Ceprate; CellPro, Bothell, WA) were
monitored for their capacity to repopulate irradiated allogeneic stroma in
human long-term bone marrow cultures. We found preservation of more than
three quarters of fully functional LTCIC in the CD34(+)-selected fractions.
Quantitation of LTCIC by limiting dilution analysis showed a 53-fold
enrichment of LTCIC from 1/9,075 in the unseparated cells to an incidence
of 1/169 in the CD34+ fractions. Thus, in a single apheresis, it was
possible to harvest a median of 1.65 x 10(4) LTCIC per kg body weight
(range, 0.71 to 3.72). In addition, in six patients, large-scale ex vivo
expansions were performed using a five-factor cytokine combination
consisting of stem cell factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and
erythropoietin (EPO), previously shown to expand committed progenitor
cells. LTCIC were preserved, but not expanded during the culture period.
Optimization of ex vivo expansion growth factor requirements using limiting
dilution assays for LTCIC estimation indicated that the five-factor
combination using SCF, IL-1, IL-3, IL-6, and EPO together with autologous
plasma was the most reliable combination securing both high progenitor
yield and, at the same time, optimal preservation of LTCIC. Our data
suggest that ex vivo-expanded CD34+ PBPCs might be able to allow long-term
reconstitution of hematopoiesis.
Volume 84,
Issue 9,
pp. 2898-2903,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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