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Phenotypic characterization of a novel bone marrow-derived cell that
facilitates engraftment of allogeneic bone marrow stem cells
CL Kaufman, YL Colson, SM Wren, S Watkins, RL Simmons and ST Ildstad
Department of Surgery, University of Pittsburgh, School of Medicine, PA.
Bone marrow transplantation is an accepted therapy for hematologic
malignancies, aplastic anemia, metabolic disorders, and solid tumors.
However, graft-versus-host disease (GVHD) and failure of engraftment have
limited the widespread application of this technology to nonmalignant
disease states. The use of purified bone marrow stem cells has been
suggested as an approach to promote engraftment yet avoid GVHD. Although
bone marrow stem cells, purified by cell sorting, engraft and repopulate
lethally irradiated genetically identical recipients, they do not engraft
in major histocompatibility complex (MHC)-disparate allogeneic recipients.
We report for the first time the characterization of a novel cell
population of donor bone marrow origin, separate from the hematopoietic
stem cell, that facilitates engraftment of purified allogeneic bone marrow
stem cells in an MHC- specific fashion without causing GVHD. Although 1,000
purified stem cells (c-kit+/Sca-1+/lineage-) reliably repopulate syngeneic
mouse recipients, 10 times that number do not engraft in MHC-disparate
allogeneic recipients. The addition of as few as 30,000 facilitating cells
(CD8+/CD45R+/TCR-) is sufficient to permit engraftment of purified stem
cells in MHC-disparate recipients. The cell surface phenotype of this
purified cellular population differs significantly from other characterized
lineages of lymphoid or myeloid origin. Based on multiparameter rare-events
cell sorting, the facilitating fraction is CD8+, CD3+, CD45R+, Thy 1+,
class IIdim/intermediate but alpha beta- TCR- and gamma delta-TCR-. This
cellular population comprises approximately 0.4% of the total bone marrow
and is separate from the hematopoietic stem cell. The coadministration of
purified facilitating cells plus stem cells to optimize engraftment yet
avoid GVHD may expand the potential application of bone marrow
transplantation to disease states in which the morbidity and mortality
associated with conventional BMT cannot be justified.
Volume 84,
Issue 8,
pp. 2436-2446,
10/15/1994
Copyright © 1994 by The American Society of Hematology
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