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Next Article 
Long- and short-lived murine hematopoietic stem cell clones individually
identified with retroviral integration markers
B Capel, RG Hawley and B Mintz
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA
19111.
The proliferative longevity of totipotent hematopoietic stem cells (THSC)
is a limiting factor in normal hematopoiesis and in therapy by cell- or
gene-replacement, but has not yet been ascertained. We have followed the
long-term fate of individual clones of mouse THSC from fetal liver or adult
bone marrow, after labeling in culture, followed by engraftment and serial
transplantation in unirradiated W/Wv-C57BL/6 hosts. The ancestor cell of
each clone and its mitotic progeny were uniquely identifiable
retrospectively by the DNA integration pattern experimentally produced by
replication-incompetent recombinant murine retroviruses. These viruses
provided physiologically neutral markers. The marked clones proved to be
derived from THSC, based on their contributions to a wide array of myeloid
and lymphoid blood lineages in the hosts. The label also identified the
target cells as the population displaying clonal succession. The various
labeled stem cell clones proliferated for substantially different periods
of time. The longest observed clone endured, after the original cell was
marked, for at least 2 1/2 years--the equivalent of a mouse's lifetime.
However, the results suggest that THSC clones are not all long-lived and
that even the longest-lived ones may not be potentially immortal. Thus, the
unpredictable lifespan of any given THSC clone indicates the desirability
of introducing multiple clones in therapeutic transplants.
Volume 75,
Issue 12,
pp. 2267-2270,
06/15/1990
Copyright © 1990 by The American Society of Hematology
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