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CORRESPONDENCE The debate about hematopoietic stem cell numbers and productive
capacity is relevant to many areas of clinical and experimental hematology. Recently, Abkowitz et al1 reported that the
total number of stem cells in mammals is conserved so that mice, cats, humans, and possibly elephants have the same-sized stem cell
pools. They emphasized that, since humans live longer than mice and
need to produce more blood cells, human stem cells must be capable of
producing many more blood cells than murine stem cells. A corollary of
this is that the frequency of stem cells in human bone marrow will be
lower than the frequency in murine bone marrow. Since we have made
similar measurements in mice and calculations in humans,2,3 we were interested in determining whether our data are consistent with those of Abkowitz et al1 and
whether the calculated numbers of stem cells in humans can account for the daily requirement to replace mature blood cells lost through senescence. Table 1 compares earlier data, obtained using 59Fe ferrokinetics to
estimate marrow cellularity and the spleen colony
(CFU-S) assay4 to measure hematopoietic stem cells
in 3 strains of mice,2 with the values reported by Abkowitz et al.1 Our data
indicate slightly greater values than Abkowitz et al,1 but
they are of the same order of magnitude. Table 1 also shows data for
the derived frequency of human hematopoietic stem cells, assuming that
the human hematopoietic stem cell population is the same size as that
of the mouse, which again is consistent with that reported by Abkowitz
et al.1
Adult humans need to produce 1 × 1011 neutrophils and
2 × 1011 red blood cells per day throughout life.
Assuming a lifespan of 80 years, this amounts to a total of
80 × 365 × 3 × 1011 (8.8 × 1015)
for these 2 lineages alone, which must be generated by 16 800 (Abkowitz et al1) or 81 000 (our data) stem
cells. Assuming steady-state stem cell kinetics5 and 100 stem cell replications per lifetime, stem cell division and
self-renewal with a probability of 0.5 will result in
1.68 × 106 to 8.1 × 106 new stem cells
available for differentiation and, ultimately, mature blood cell
formation. Consequently, each of these stem cells must be responsible
for producing 1.1 × 109 to 5.2 × 109
mature cells. It is noteworthy therefore that Brummendorf et al6 reported that single stem cells generate, on average,
nearly 109 CD34+CD38 Insufficient data are available to estimate the size of the stem cell
pool and kinetic parameters in elephants accurately (Table 2). But
simple calculations of the possible frequency and productive capacity
of elephantine stem cells can be made. The data in Table 1 and Abkowitz
et al1 indicate that mice, cats, and humans have on the
order of 1 × 1010 to 2 × 1010
bone marrow cells per kilogram of body weight. If the same is true of
elephants, a large African elephant of 7 500 kg (Table 2) could have
as many as 1.5 × 1014 bone marrow cells. The
corresponding frequencies of stem cells in such animals would be 1 to 8 per 1010 if all species have the same number.1
Furthermore, elephants have many more blood cells than mice or humans
(Table 1), up to 10 × 1012. If red and white cell
kinetics are similar in humans and elephants, who live about the same
length of time, a large African elephant will need to produce
17.5 × 1020 cells in a lifetime. This number corresponds
to 2 × 1014 to 10 × 1014 cells per stem
cell.
In summary, the experimental and theoretical estimates of stem cell pool size in humans are not inconsistent with lifelong requirements for blood cell production sustained by a self-renewing stem cell population. Nor do the values we have derived appear to be inconsistent with the idea that mice, cats, humans, and elephants could have similar numbers of stem cells.1
Myrtle Y. Gordon, John L. Lewis, and Stephen B. Marley
References
1.
Abkowitz JL, Catlin SN, McCallie MT, Guttorp P.
Evidence that the number of hematopoietic stem cells per animal is conserved in mammals.
Blood.
2002;100:2665-2667 2. Coggle JE, Gordon MY. Quantitative measurements on the haemopoietic systems of three strains of mice. Exp Hematol. 1975;3:181-186[Medline] [Order article via Infotrieve]. 3. Gordon MY, Blackett NM. Reconstruction of the hematopoietic system after stem cell transplantation. Cell Transplant. 1998;7:339-344[CrossRef][Medline] [Order article via Infotrieve]. 4. Till JE, McCulloch EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961;14:213-222[Medline] [Order article via Infotrieve]. 5. Gordon MY, Blackett NM. Some factors determining the minimum number of cells required for successful clinical engraftment. Bone Marrow Transplant. 1995;15:659-662[Medline] [Order article via Infotrieve].
6.
Brummendorf TH, Dragowska W, Zijlmans JMJM, Thornbury G, Lansdorp PM.
Asymetric cell divisions sustain long-term hematopoiesis from single-sorted human fetal liver cells.
J Exp Med.
1998;188:1117-1124
7.
Wang JCY, Doedens M, Dick JE.
Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow as measured by the quantitative in vivo SCID repopulating cell assay.
Blood.
1997;89:3919-3924   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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cells in
vitro and the greatest number observed was more than 1012.
The corresponding stem cell frequency would be 1 in
5 × 108 to 10 × 108. As noted by Abkowitz
et al,
