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Permanent loss in stem cell self renewal capacity following stress to the
marrow
P Mauch, M Rosenblatt and S Hellman
Department of Radiation Therapy, Harvard Medical School, Boston, MA.
A technique of irradiating the entire mouse except for one hind limb was
developed to provide repeated proliferative demand on the stem cell pool.
Animals received 200 cGY weekly for a total dose of 3,400 to 4,000 cGy.
During irradiation, shielded bone marrow cellularity was similar to that of
unirradiated controls. Shielded marrow colony- forming unit (CFUs) content
increased while marrow CFUs self renewal capacity decreased as compared
with unirradiated age-matched controls. Following irradiation experimental
animals were monitored monthly for 10 to 12 months for marrow cellularity,
CFUs content, and self renewal capacity. Shielded marrow cellularity and
CFUs content remained elevated over age-matched controls throughout the
period of observation. These findings are compatible with the requirement
of the shielded hind limb to provide hematopoietic support for the
remainder of the animal. Shielded marrow self renewal capacity, a
measurement reflecting primitive hematopoietic stem cell function, remained
depressed and did not recover with time. These experiments provide evidence
for there being limitations on the self renewal capacity of the stem cell
compartment. While the small amount of shielded marrow had sufficient
capacity to support the animal its average self renewal capacity was
permanently reduced.
Volume 72,
Issue 4,
pp. 1193-1196,
10/01/1988
Copyright © 1988 by The American Society of Hematology
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