Abstract
Long-term hematopoietic stem cells (LT-HSC) and short-term hematopoietic stem cells (ST-HSC) have been characterized as having markedly different in vivo repopulation, but similar in vitro growth in liquid culture. These differences could be due to differences in marrow homing. We evaluated this by comparing results when purified ST-HSC and LT-HSC were administered to irradiated mice by three different routes: intravenous, intraperitoneal, and directly into the femur. Purified stem cells derived from B6.SJL mice were competed with marrow cells from C57BL/6J mice into lethally irradiated C57BL/6J mice. Serial transplants into secondary recipients were also carried out. We found no advantage for ST-HSC engraftment when the cells were administered intraperitoneally or directly into femur. However, to our surprise, we found that the purified ST-HSC were not short-term in nature but rather gave long-term multilineage engraftment out to 387 days, albeit at a lower level than the LT-HSC. The ST-HSC also gave secondary engraftment. These observations challenge current models of the stem cell hierarchy and suggest that stem cells are in a continuum of change.
Highlights
Elegant work, utilizing fluorescently labeled monoclonal antibodies and fluorescence-activated cell sorting (FACS), has progressively characterized the multilineage repopulation potential of different marrow cell populations
The isolated Long-term hematopoietic stem cells (LT-HSC) or STHSC/multipotent progenitor (MPP) were competed against C57BL/6J marrow into lethally irradiated C57BL/6J host mice
Our studies indicate that changes in the route of administration of short-term hematopoietic stem cells (ST-HSC)/MPP to intraperitoneal or intrafemoral routes, in general, did not result in engraftment equivalent to that seen when LT-HSC were administered intravenously, indicating that differences between engraftment of these cell types was not due to differences in homing efficiency
Summary
Elegant work, utilizing fluorescently labeled monoclonal antibodies and fluorescence-activated cell sorting (FACS), has progressively characterized the multilineage repopulation potential of different marrow cell populations. This work has formed the basis for a detailed marrow stem/progenitor cell hierarchy [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23] in which the most primitive stem cells differentiate into progressively more mature marrow cells with gains of specific function and loss of proliferative, renewal, and total differentiation potential In this generally accepted model, the most primitive cell is the long-term hematopoietic stem cell separated on the basis of lineage negative status (Lin2) and expression of the surface epitopes c-kit and Sca-1 with either intermediate Thy-1.1 expression or absence of Flk-2 [7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
