The human hematopoietic stem cell in vitro and in vivo.
A quantitative assay for a primitive human hematopoietic cell has been developed. The cell identified has been assigned the operational designation of long-term culture (LTC)-initiating cell based on its ability when cultured on supportive fibroblast monolayers to give rise to daughter cell(s) detectable by standard in vitro colony assays. Three lines of evidence support the view that the LTC-initiating cell assay may allow the relatively specific enumeration of totipotent cells with in vivo reconstituting potential. These involve the demonstration: (1) that conditions in analogous murine long-term cultures stimulate the extensive amplification (self-renewal) of some totipotent long-term repopulating cells, (2) that most of the LTC-initiating cells in normal human bone marrow are phenotypically different from most of the colony-forming cells present in the same cell suspensions in their possession of a number of characteristics specifically associated with transplantable stem cells; and (3) that cultured marrow cells from patients with chronic myeloid leukemia which, after maintenance under LTC conditions for 10 days contain some normal LTC-initiating cells but no detectable leukemic LTC-initiating cells, can after autografting reconstitute the hematopoietic system with normal cells.
Eaves
C J
CJ
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Sutherland
H J
HJ
Udomsakdi
C
C
Lansdorp
P M
PM
Szilvassy
S J
SJ
Fraser
C C
CC
Humphries
R K
RK
Barnett
M J
MJ
Phillips
G L
GL
Eaves
A C
AC
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002478:Cells, Cultured / Q000637:transplantation; D003114:Colony-Forming Units Assay; D046508:Culture Techniques / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D051379:Mice