In vivo expansion of hemopoietic stem cells.
Under conditions of steady-state hemopoiesis, a small fraction of immature hemopoietic cells, including stem cells, circulates in peripheral blood (PB). In rhesus monkeys, a median number of 1.2 x 10(7)/l CD34+ cells was observed as opposed to a median number of 1.5 x 10(9)/l in aspirated bone marrow (BM). The concentration of circulating CD34+ cells is therefore approximately two logs less than that in BM. Since a 4-kg rhesus monkey has an estimated number of 3 x 10(10) BM cells and approximately 300 ml of blood, the fraction of CD34+ cells that circulates can be estimated at approximately 0.4% of the total pool of CD34+ cells. During hemopoietic reconstitution following a cytotoxic insult such as results from a midlethal dose of TBI, PB CD34+ cell numbers appeared to be correlated to those of BM, suggesting that PB CD34+ cells may reflect reconstitution of BM CD34+ cells. Reconstitution of BM immature cells can be accelerated by treatment with pharmacological doses of growth factors, resulting in largely expanded immature cell populations within a few weeks after TBI. Growth factors observed to exert such an effect included, notably, thrombopoietin. Such an acceleration can be monitored by daily assessment of circulating CD34+ cells. Expansion of immature circulating cells indicates expansion of similar cells in the bone marrow rather than growth factor-induced selective mobilization of immature cells.
Wagemaker
G
G
Institute of Hematology, Erasmus Universiteit Rotterdam, The Netherlands.
Hartong
S C
SC
Neelis
K J
KJ
Egeland
T
T
Wognum
A W
AW
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000528:radiation effects; D006133:Growth Substances / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology* / Q000528:radiation effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000528:radiation effects; D008253:Macaca mulatta; D008297:Male; D014916:Whole-Body Irradiation
D018952:Antigens, CD34; D006133:Growth Substances