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Thrombopoietin, kit Ligand, and flk2/flt3 Ligand Together
Induce Increased Numbers of Primitive Hematopoietic Progenitors From
Human CD34+Thy-1+Lin Cells
With Preserved Ability to Engraft SCID-hu Bone
Karin M. Luens,
Marilyn A. Travis,
Ben P. Chen,
Beth L. Hill,
Roland Scollay, and
Lesley J. Murray
From SyStemix a Novartis Company, Cell Therapy Research, Palo Alto,
CA.
CD34+Thy-1+Lin cells are
enriched for primitive hematopoietic progenitor cells (PHP), as defined
by the cobblestone area-forming cell (CAFC) assay, and for bone marrow
(BM) repopulating hematopoietic stem cells (HSC), as defined by the in
vivo SCID-hu bone assay. We evaluated the effects of different cytokine
combinations on BM-derived PKH26-labeled
CD34+Thy-1+Lin cells in
6-day stroma-free cultures. Nearly all (>95%) of the CD34+Thy-1+Lin cells divided
by day 6 when cultured in thrombopoietin (TPO), c-kit ligand (KL), and
flk2/flt3 ligand (FL). The resulting CD34hi
PKHlo (postdivision) cell population retained a high CAFC
frequency, a mean 3.2-fold increase of CAFC numbers, as well as a
capacity for in vivo marrow repopulation similar to freshly isolated
CD34+Thy-1+Lin cells.
Initial cell division of the majority of cells occurred between day 2 and day 4, with minimal loss of CD34 and Thy-1 expression. In contrast,
cultures containing interleukin-3 (IL-3), IL-6, and leukemia inhibitory
factor contained a mean of 75% of undivided cells at day 6. These
CD34hi PKHhi cells retained a high frequency of
CAFC, whereas the small population of CD34hi
PKHlo postdivision cells contained a decreased frequency of
CAFC. These data suggest that use of a combination of TPO, KL, and FL
for short-term culture of
CD34+Thy-1+Lin cells
increases the number of postdivision PHP, measured as CAFC, while
preserving the capacity for in vivo engraftment.
Blood, Vol. 91 No. 4 (February 15), 1998:
pp. 1206-1215
© 1998 by The American Society of Hematology.
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