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CD34+ marrow cells, devoid of T and B lymphocytes, reconstitute stable
lymphopoiesis and myelopoiesis in lethally irradiated allogeneic baboons
RG Andrews, EM Bryant, SH Bartelmez, DY Muirhead, GH Knitter, W Bensinger, DM Strong and ID Bernstein
Program in Pediatric Oncology, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
CD34+ cells devoid of detectable mature and immature T and B lymphocytes,
expressing the CD2, CD10, and CD20 antigens, were isolated from marrows of
three pairs of sex-mismatched, mixed lymphocyte culture (MLC) nonreactive,
sibling baboons. Reciprocal transplants were performed between members of
each pair, using the sex chromosomes, identified by standard cytogenetic
techniques, as markers of the transplanted cells. Five animals from these
three pairs were transplanted with 0.6 to 2.1 x 10(6)/kg of isolated
cryopreserved and/or fresh isolated cells that were greater than 95% to 97%
CD34+. Before transplantation, animals were treated with either single (920
or 1,020 cGy) or split (700 cGy x 2) dose total body irradiation. All
animals engrafted with donor cells, as demonstrated by cytogenetic analysis
of bone marrow metaphase cells 4 weeks after transplantation, with days to
white blood cell count (WBC) greater than 500 being 19 +/- 2, to WBC
greater than 1,000 23 +/- 2, to absolute neutrophil count greater than 500
24 +/- 3, and to platelets greater than 20,000 30 +/- 7. Three animals died
of infectious-related complications at 34, 42, and 109 days after
transplantation with evidence of host and donor cells (mixed chimerism) in
marrow. Two animals remain alive and healthy more than 545 and 455 days
after transplantation with stable mixed chimerism in marrow and blood. For
these two animals, cytogenetic analysis of granulocyte/macrophage and
erythroid colonies derived from marrow precursors between weeks 25 and 42
posttransplant showed evidence of mixed chimerism. Cytogenetic studies of
CD2+ T cells and CD20+ B cells isolated from blood of these two animals
between weeks 21 and 51 posttransplant showed the presence of mixed
chimerism in both lymphocyte populations. Thus, isolated allogeneic CD34+
marrow cells devoid of detectable mature and immature T and B lymphocytes
can engraft and reconstitute stable long-term myelopoiesis and
lymphopoiesis in lethally irradiated baboons. These results are consistent
with the hypothesis that CD34+ marrow cells contain pluripotent
hematopoietic stem cells capable of fully reconstituting
lymphohematopoiesis in the transplanted host.
Volume 80,
Issue 7,
pp. 1693-1701,
10/01/1992
Copyright © 1992 by The American Society of Hematology
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